Immune Dysregulation

A Mouse Model for the Immune Dysregulation Subtype of Autism « Lisa Ackerman – Real Help Now.

I can’t really tell you how much I wish this were more well-known. I know that I can’t make anyone else really feel the same way, either. Not in the meaningful way I’d like, at least. I don’t think anyone can feel it properly unless they’ve been there.

The medical community might think it’s not worth exploring but try asking the mom that had a miscarriage two months before getting pregnant with her ASD son. The one whose miscarried pregnancy was completely not right in every way from the very start. The pregnancy that was likely miscarried for some sort of immune dysfunction.

The bad pregnancy that probably affected the pregnancy immediately following it two months later.

Whatever happened to my immune system happened to him. He was born with those immune problems and spent the first three years of his like always sick. Vaccines (especially the Hep B) played such a large role in keeping him sick and making him sicker. Each shot make him slip further away.

I find myself having many of the same issues but I’m older, I’m not developing and learning and becoming a person. I already know how to behave appropriately so when these issues arise in me, I already know how to handle them, or at least control them. I already know it’s not normal.

He was an infant with no prior knowledge. He was a brand new being and all these things were imprinting in his brain as being normal.

And now his immune system is shot and his viral titers are crazy. He will not likely ever be able to stop taking antivirals and antifungals. It’s just an unfortunate reality. His recovery is completely reliant upon them. Without them, his ASD symptoms return. It’s been proven over and over in him. Take antivirals and symptoms disappear. Remove antivirals and symptoms return. We’ve replicated this scenario every year.

I’m not sure how much more proof anyone could need. You don’t even have to believe that he has immune dysfunction. All you need to do is believe that antivirals clearly improve his ASD status. He goes from mostly recovered while on it to not at all recovered when off. We can do this over and over and over and over. There’s obviously some kind of correlation that should give any doctor pause.

And yet I can’t get many western medical professionals to “get it” and understand autism is more than a set of psychological symptoms. We’re fortunate that we’ve got a wonderful ped and a wonderful DAN doctor. But it took us a long time to find a doctor that looked at the results instead of towing the party line.

Medicine should be progressive. We should be open to learning, not pressured by organizations and companies with an agenda.

These are the types of studies we need more doctors to read. We need more doctors that will employ critical thinking skills instead of looking up the same tired answers in a medical book or rehashing the same biased information from what has been proven many times over to be biased journals.

Maternal (possibly even paternal) immune dysregulation should matter. Immune dysregulation as a subtype of ASD should matter.

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Scientist First to Characterize Novel Syndrome of Allergy, Apraxia, Malabsorption

Newswise – A landmark study conducted by Children’s Hospital & Research Center Oakland is the first to reveal a new syndrome in children that presents with a combination of allergy, apraxia and malabsorption. Autism spectrum disorders were variably present. Verbal apraxia has until now been understood to be a neurologically based speech disorder, although hints of other neurological soft signs have been described. The new study, led by Children’s Hospital & Research Center Oakland scientist and pediatric emergency medicine physician, Claudia Morris, MD, and Marilyn C. Agin, MD, a neurodevelopmental pediatrician at Saint Vincent Medical Center in New York, however, suggests that the symptoms of verbal apraxia are, at least for a sub-group of children, part of a larger, multifactorial, neurologic syndrome involving food allergies/gluten-sensitivity and nutritional malabsorption.
“While it is critical to treat verbal apraxia symptoms that often include severe delays in expressive speech production with speech therapy, we need to start asking why these kids are having these problems in the first place so that we can identify mechanisms we can actually target to treat the cause of the symptoms,” says Dr. Morris.

Published in the July/August issue of Alternative Therapies in Health and Medicine, the new study takes a major step toward identifying the potential mechanisms that may contribute to apraxia symptoms. In the study, Dr. Morris collected information from nearly 200 families with children who suffered from verbal apraxia in order to better characterize the symptoms and metabolic anomalies of a subset of children. The data clearly demonstrated a common cluster of allergy, apraxia and malabsorption, along with low muscle tone, poor coordination and sensory integration abnormalities. In addition, Dr. Morris was able to gather laboratory analyses in 26 of the children, which revealed low carnitine levels, abnormal celiac panels, gluten sensitivity, and vitamin D deficiency among others. All children genetically screened carried an HLA gene associated with gluten sensitivity and celiac disease. “The sample size is still small and should be interpreted with caution,” says Dr. Morris. “However this is of particular interest given the recent publication by Eaton and colleagues in the July 6 online edition of Pediatrics demonstrating a greater than 3-fold risk of autism in children born to mothers diagnosed with celiac disease. This brings some credibility to the anecdotal reports of gastrointestinal and behavioral improvements in children with autism spectrum disorders and/or verbal apraxia when eliminating gluten from their diets. Although the implications of these observations remain to be determined, this association and the utility of dietary modifications warrant further investigation, particularly if we can identify a genetically vulnerable group”.

Most significantly, the data indicate that the neurologic dysfunction represented in the syndrome overlaps the symptoms of vitamin E deficiency. While low vitamin E bioavailability may occur due to a variety of different causes, neurological consequences are similar, regardless of the initiating trigger. The study suggests that vitamin E could be used as a safe nutritional intervention that may benefit some children. Growing evidence support the benefits of omega 3 fatty acid supplementation in a number of neurodevelopmental disorders. Anecdotally children with verbal apraxia will often demonstrate leaps in their speech production when taking high-quality fish oil. The addition of vitamin E to omega 3 fatty acid supplementation in this cohort of children induced benefits that exceeded those expected from just speech therapy alone, according to parental report.

“While data from a case series is by no means conclusive, the results clearly point to the need for further attention to this poorly understood disorder, and a placebo-controlled study to investigate the potential role of vitamin E and omega 3 supplementation in this group of children,” says Dr. Morris.

She points out that it is equally important for children given an apraxia diagnosis to receive a more comprehensive metabolic evaluation than what is current practice. Many of the nutritional deficiencies like low carnitine, zinc and vitamin D are easily treated. By not addressing the nutritional deficiencies, the child will continue to suffer from significant medical consequences of those deficiencies. The first step is to identify and treat the deficiencies. The next step is to try to figure out why they have these deficiencies and a fat malabsorption syndrome in the first place. However, Dr. Morris does advise families to work closely with a physician rather than trying promising but unproven interventions on their own.

In the mean time, however, Dr. Morris’s study provides the essential foundation for identifying the children who may need these treatments.

“By identifying these early red flags of the syndrome, we’ve provided a way to get these kids treatment at the earliest possible moment. While 75 percent of the time kids identified as late bloomers really are just that, 25 percent of the time there is a true pathologic condition. To miss it is to miss critically valuable time for early intervention. If a child has all these symptoms, chances are they are going to fall into the 25 percent who have a condition that needs further evaluation and treatment.”

About Children’s Hospital & Research Center Oakland
Children’s Hospital & Research Center Oakland is Northern California’s only freestanding and independent children’s hospital. Children’s is the leader in many pediatric specialties including neonatology, cardiology, neurosurgery and intensive care. The hospital is a designated Level 1 pediatric trauma center and has the largest pediatric critical care facility in the region. Children’s Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,611 employees and an operating budget of $312 million. Children’s research arm, Children’s Hospital Oakland Research Institute, is internationally renowned in bridging state of the art basic science and clinical research for the treatment and prevention of human disease. With about 300 staff members and an annual budget of approximately $50 million, CHORI is ranked among the top ten research institutes in National Institutes of Health funding to children’s hospitals. CHORI is a leader in translational research, providing cures for diseases, developing new vaccines for infectious diseases and discovering new treatment protocols for previously fatal or debilitating conditions such as cancer, sickle cell disease and thalassemia, diabetes, asthma, HIV/AIDS, pediatric obesity, nutritional deficiencies, birth defects, hemophilia and cystic fibrosis.

Source: Children’s Hospital & Research Center Oakland

Chronic Mycoplasmal Infections in Gulf War Veterans’ Children and Autism Patients

Garth L. Nicolson, PhD, 1 Paul Berns, MD, 1 Robert Gan, MD, 1 and Jeorg Haier, MD, PhD2

1The Institute for Molecular Medicine, Huntington Beach, California, USA
16371 Gothard Street H
Huntington Beach, California 92647
Phone: +1 714 596-6636 Fax: +1 714 596-3791;

Email: gnicolson@immed.org Website: http://www.immed.org

2Department of Internal Medicine, and Department of Surgery, Wilhelm-University, Munster, Germany

Abstract

Autism patients have systemic bacterial, viral and fungal infections that may play an important part in their illnesses. We found that immediate family members of veterans diagnosed with Gulf War Illnesses (GWI) often complain of fatigue and other problems, and upon analysis they report similar signs and symptoms as their veteran family members, except that their children are often diagnosed with Autism. Since a relatively common finding in GWI patients is a bacterial infection due to Mycoplasma fermentans, we examined military families (149 patients: 42 veterans, 40 spouses, 32 other relatives and 35 children with at least one family complaint of illness) selected from a group of 110 veterans with GWI who tested positive (~42%) for mycoplasmal infections. Consistent with previous results, over 80% of GWI patients who were positive for blood mycoplasmal infections had only one Mycoplasma species, M. fermentans. In healthy control subjects the incidence of any mycoplasmal infection was ~8.5% and none were found to have multiple mycoplasmal species (P<0.001). In 107 family members of mycoplasma-positive GWI patients there were 57 patients (53%) that had essentially the same signs and symptoms as the veterans and were diagnosed with Chronic Fatigue Syndrome (CFS/ME) and/or Fibromyalgia Syndrome. The majority of children (n=35) in this group were diagnosed with Autism. Most of these CFS or Autism patients also had mycoplasmal infections compared to the few non-symptomatic family members (P<0.001), and the most common species found was M. fermentans. In contrast, in the few non-symptomatic family members that tested mycoplasma-positive, the Mycoplasma species were usually different from the species found in the GWI patients. The results suggest that a subset of GWI patients have mycoplasmal infections, and these infections can be transmitted to immediate family members who subsequently display similar signs and symptoms, except for their children who are often diagnosed with Autism. In a separate study in Central California we examined a group of Autism patients and also found a high incidence of mycoplasmal infections, but in contrast to the military families a variety of Mycoplasma species were detected.

Keywords: Autism, fatiguing illnesses, mycoplasmal infections

1. Introduction

Children with Autism generally suffer from an inability to properly communicate, form relationships with others and respond appropriately to their environment. Autism patients do not all share the same signs and symptoms but tend to share certain social, communication, motor and sensory problems that affect their behavior in predictable ways. These children often display repetitive actions and develop troublesome fixations with specific objects, and they are often painfully sensitive to certain sounds, tastes and smells [1]. These signs and symptoms are thought to be due to abnormalities in brain function or structure. In some patients there are also a number of other less specific chronic signs and symptoms. Among these are fatigue, headaches, gastrointestinal and vision problems and occasional intermittent low-grade fevers and other signs and symptoms that are generally excluded in the diagnosis of Autism.

Autism causes are unknown and may include genetic defects, heavy metal, chemical and biological exposures, among others, and are probably different in each patient. However, among Autism patients there may be similarities in genetic defects and environmental exposures [2, 3] that are important in patient morbidity (sickness) or in illness progression. Other chronic illnesses have some of the same chronic signs and symptoms, suggesting that there may be some overlap in the underlying causes of these conditions or at least in the factors that cause illness or morbidity or illness progression.

The signs and symptoms in many, perhaps even a majority, of chronic illness patients may be due, in part, to systemic chronic infections (bacteria, viruses, fungi) that can penetrate into the central nervous system (CNS). Such infections often follow acute or chronic heavy metal, chemical, biological (viral, bacterial, fungal infections) exposures or environmental insults or even multiple vaccines that have the potential to suppress the immune system and leave children susceptible to opportunistic infections [2-5]. These illnesses generally evolve slowly over time in a multi-step process that may require genetic susceptibility along with multiple toxic exposures.

Chronic infections may be an important element in the development of Autism. Such infections are usually held in check by immune surveillance, but they can take hold and become a problem if they can avoid host immunity and penetrate and hide in various tissues and organs, including cells of the CNS and peripheral nervous system. When such infections occur, they may cause many of the complex signs and symptoms seen in various chronic illnesses [5, 6]. Changes in environmental responses and increased titers to various endogenous viruses as well as bacterial and fungal infections have been commonly seen in chronic illnesses [5, 6].

One type of airborne infection that has received renewed interest of late as an important cause, cofactor or opportunistic infection in various chronic illnesses is represented by relatively primitive intracellular bacteria. These bacteria, principally Mycoplasma, Chlamydia, Coxiella, Brucella, Borrelia, etc. are not as well known as other agents in causing disease but are now considered important emerging pathogens in various chronic diseases. In fact, a majority of patients with various chronic illnesses show evidence of these infections in their blood [5, 6].

Autism patients often show their first signs and symptoms after multiple childhood immunizations [2]. Rimland [2] noted that the sharp rise in Autism rates only occurred after the multiple vaccine MMR came into widespread use. In the U.S. children typically receive as many as 33 vaccines, a dramatic increase in the use of childhood vaccines over the last few decades. Such vaccines often contain mercury and other preservatives [3]. Commercial vaccines have also been examined for contaminating microorganisms, and one study found that approximately 6% of commercial vaccines were contaminated with Mycoplasmas [6]. Thus we examined the extent of mycoplasmal infections in patients with Autism. We were aided in this examination by data that we collected on families of Gulf War veterans where there was a high incidence of Autism in their children [8].

2. Methods

Patients

Gulf War veterans with GWI and a positive test for mycoplasmal infection and their immediate family members (149 patients: 42 veterans, 40 spouses, 32 other relatives and 35 children) were enrolled in a Gulf War Illnesses family study [8]. Seventy age-matched healthy volunteers were recruited and used as control subjects. In the Central California Autism study 28 children diagnosed with Autism were enrolled. All subjects underwent a medical history and routine laboratory tests. If necessary, medical records were also reviewed to determine if patients suffered from organic or psychiatric illnesses that could explain their symptoms [8]. All subjects completed an illness survey questionnaire, which included demographic information, known environmental exposures, dates of illness onset, health status before and immediately after the Gulf War and current health status. We also used an Autism Illness Survey Form developed by the Autism Institute (San Diego, CA). Control subjects had to be free of diagnosed disease other than Autism for at least three months prior to data collection.

Blood Collection

Blood was collected in EDTA-containing tubes, immediately brought to ice bath temperature and shipped with wet ice by air courier to the Institute for Molecular Medicine for analysis. All blood samples were blinded. Whole blood was used for preparation of DNA using Chelex as previously described [8, 9]. Multiple Mycoplasma tests were performed on all patients and control subjects [8, 9].

Amplification of Gene Sequences by PCR

Amplification of the target gene sequences by Polymerase Chain Reaction (PCR) was accomplished as previously described [8, 9]. Negative and positive controls were present in each experimental run. The amplified samples were separated by agarose gel electrophoresis. After denaturing and neutralization, Southern blotting was performed to confirm the PCR product [8, 9]. Multiple PCR primer sets were used for each species tested to minimize the chance that cross-reacting microorganisms were detected.

Statistics

Subjects’ demographic characteristics were assessed using descriptive statistics and students’ t-tests (independent samples test, t-test for equality of means, 2-tailed). The 95% confidence interval was chosen. Pearson Chi-Square test was performed to compare prevalence data between patients and control subjects. Illness survey data were statistically analyzed using Spearman Rank correlation and Mann-Whitney tests.

3. Results

Gulf War Illness Family Study

As found previously [10, 11], veterans of the Gulf War with chronic fatiguing illness (GWI) exhibited multiple signs and symptoms. Upon examination, the signs and symptoms of GWI were indistinguishable from civilian patients diagnosed with CFS/ME, expect for symptomatic children aged 3-12 who were also diagnosed with Autism or Attention Deficit Hyperactivity Disorder (ADHD) [8].

Figure 1. Percent incidence of mycoplasmal infections in family members of veterans with Gulf War Illnesses.

Similar to previous studies [10, 11], 45 of 110 GWI patients or ~42% had mycoplasmal infections (Figure 1), and almost all of these (37 out of 45 or ~82%) were single infections (one species of mycoplasma) [8]. M. fermentans was found in ~85% of these single infection cases (Figure 2). When the few multiple infection cases were examined, most were found to have combinations of M. fermentans plus either M. pneumoniae, M. hominis or M. genitalium (Figure 2). In contrast, in healthy control subjects only 6 of 70 subjects (8.5%) were positive for any mycoplasmal infection, and all of these were single species infections of various types [8]. Comparing GWI patients and non-symptomatic control subjects, there was a significant difference in the incidence of mycoplasmal infections (P<0.001). Differences in infection incidence or species of mycoplasmal infection between male and female GWI patients or control subjects were not seen [8].

In family members of Gulf War veterans with GWI there was evidence of illness transmission. These families were not randomly chosen; they were families in which one or more veteran members were found to be positive for a mycoplasmal infection and one or more non-veteran family members reported illnesses. We found that 57/107 (53.2%) of these family members from families with one or more Gulf War veteran diagnosed with GWI and with a positive test for a mycoplasmal infection showed symptoms of CFS/ME. Among the CFS-symptomatic family members, most (40/57 or 70.2%) had mycoplasmal infections compared to the few non-symptomatic family members who had similar mycoplasmal infections (6/50 or 12%) (Figure 1). When the incidence of mycoplasmal infection was compared within families, the CFS family members were more likely to have mycoplasmal infections compared to non-symptomatic family members (P<0.001). Symptomatic children (mostly diagnosed with Autism and ADHD) were also infected with mycoplasmas at high incidence (Figure 1), but this was not seen in aged-matched control subjects (data not shown). Although some non-symptomatic family members did have mycoplasmal infections (5/50 or 10%), this was not significantly different from the incidence of mycoplasmal infections in healthy control subjects (6/70 or 8.5%) (Figure 1).

Figure 2. The incidence of various mycoplasma species in Gulf War Illnesses. All cases of multiple mycoplasmal infections were combinations with M. fermentans.

The mycoplasma infection types were also similar between GWI patients and their CFS-symptomatic family members. In 45 mycoplasma-positive CFS-symptomatic family members, most (31 out of 40 or 77.5%) had single species infections, similar to the mycoplasma-positive Gulf War veterans (37 out

of 45 or 82%). Most mycoplasma-positive GWI patients as well as mycoplasma-positive family members with CFS or children diagnosed with Autism had M. fermentans (Figure 3). We did not find differences in the incidence of infection or type of infections between males and females, children versus adults or spouses versus other family members (data not shown). However, similar to previous reports, the time of onset of CFS illness after the Gulf War tended to be shorter in spouses than other family members, but these differences did not achieve significance [8].

Figure 3. The incidence of various mycoplasma species in family members of veterans with Gulf War Illnesses. All cases of multiple mycoplasmal infections were combinations of M. fermentans.

Autism Study

We next examined a small cohort of Autism patients in Central California. This comprised 28 patients aged 3-12 who were diagnosed with Autism. Most of these children had at least one parent with a chronic illness, and the most common diagnosis of adults or adolescents in the same family was CFS/ME or Fibromyalgia Syndrome. When the Autism patients were examined for mycoplasmal infections, 15 children tested positive (54%) for mycoplasmal infections. However, in contrast to the children of GWI patients who for the most part had only one type of mycoplasmal infection, M. fermentans, the Central California group that tested positive for mycoplasmal infections had a variety of different species of mycoplasmas (Figure 4). We also tested a few siblings without apparent signs and symptoms, and for the most part few had these infections (5/41 subjects or 12%). Similar results were found in the Gulf War veterans’ families where 12% of non-symptomatic family members had mycoplasmal infections [8]. The finding of a variety of different species of mycoplasmas in Autism patients was similar to the results in a number of studies on CFS/ME and FMS patients where multiple infections of various species of mycoplasmas were commonly found [9].

Figure 4. The incidence of various mycoplasma species in patients with Autism from Central California. All cases of multiple mycoplasmal infections were combinations of M. fermentans.

4. Discussion

The data presented here and elsewhere [8] document that the chronic infections found in Gulf War veterans with GWI can be found in symptomatic family members, including their children with Autism. Because of the size of this cohort, we cannot extrapolate our results to the entire GWI patient population or their family members [8]. First, our patient sample was not randomly selected. The presence of a positive mycoplasma test result on a veteran with GWI who reported illness in his/her immediate family formed the criteria for inclusion in the study. Although chronic illnesses in immediate family members were commonly seen in our study, which examined families of mycoplasma-positive GWI patients, these illnesses are expected to be more difficult to find in the general GWI population where chemical, radiological and environmental exposures probably account for the majority of cases [17]. Second, GWI patients and their family members were recruited from veterans groups, word of mouth, physician referrals and the Institute for Molecular Medicine website (www.immed.org); they were not recruited from specific military units. Although some of these patients were examined by physicians at our associated clinics, most were seen by their own private physicians. Fourth, the validity of PCR techniques for Mycoplasma species detection has been questioned. In our studies, however, the sensitivity and specificity of the PCR method for Mycoplasma species detection were determined by examining serial dilutions of purified DNA from M. fermentans, M. pneumoniae, M. hominis and M. genitalium or the microorganisms themselves in blood samples. The primers produced the expected amplification product size in all test species, which was confirmed by hybridization using the appropriate 32P-labeled internal probe. Amounts as low as a few fg of purified DNA were detectable for all species with the specific internal probes. There was no cross-reactivity between the internal probes of one species and the PCR product from another species [12].

Symptomatic family members of GWI patients were diagnosed with CSF or a related fatiguing illness, Fibromyalgia Syndrome (FMS), but their symptomatic children were usually diagnosed with Autism or ADHD [8]. At least 50-60% of CFS and/or FMS patients are positive for mycoplasmal infections [5, 6, 9, 12-16]. However, in contrast to mycoplasma-positive GWI patients and their mycoplasma-positive family members diagnosed with CFS/ME or Autism, several species of mycoplasmas in addition to M. fermentans were found in CSF/ME and FMS patients from non-military families [12-16]. Similarly, we also found various species of mycoplasma in children diagnosed with Autism from Central California.

There could be different sources of the mycoplasmal infections found in GWI patients [17]. An important possible source for the mycoplasmal infections found in GWI patients is the multiple vaccines that were administered during the time of deployment to the Persian Gulf. A strong association has been found between GWI and the multiple vaccines that were administered during deployment [18-20]. Steele [20] found a three-fold increased incidence of GWI in non-deployed veterans who had been vaccinated in preparation for deployment, compared to non-deployed, non-vaccinated veterans, and Mahan et al. [21] found a two-times higher incidence of GWI signs and symptoms in veterans who recalled receiving anthrax vaccinations versus those who thought they had not. Although the mycoplasmal infections found in GWI patients could have come from several sources, including offensive Biological Warfare attacks [22], we consider the most likely source of the mycoplasmal infections in GWI patients was the multiple vaccines administered during deployment [17]. Indeed, the signs and symptoms that have developed in Armed Forces personnel who recently received the anthrax vaccine are similar to those found in GWI patients. On some military bases this has resulted in chronic illnesses in as many as 7-10% of personnel receiving the vaccine [23]. Undetectable microorganism contaminants in vaccines could have resulted in illness, and this may have been more likely in individuals with compromised immune systems caused by chemical and other exposures [17]. Similarly, the onset of Autism in children from civilian families is also associated with multiple vaccines [2]. Mycoplasmal infections could have originated from the vaccines or from opportunistic infections in immune suppressed children.

Contamination with mycoplasmas has been found in commercial vaccines. In one study 6% of commercial vaccines were found to be contaminated with mycoplasmas [7]. Thus the vaccines used in the Gulf War should be considered as a possible source of the chronic infections found in mycoplasma-positive GWI patients and by airborne transmission in their mycoplasma-positive, CFS-symptomatic family members. And the appearance of mycoplasmal infections in children diagnosed with Autism from civilian families may eventually be linked to the multiple vaccines received during childhood either as a source or from opportunistic infections in immune suppressed recipients of multiple vaccines.

5. References

[1] Neuwirth S. Autism. NIH Publication No. 97-4023, 1997.

[2] Rimland B. The Autism epidemic, vaccinations and mercury. J. Nut. Environ. Med. 2000;10:261–6.

[3] Downing D. Mercury again. J. Nut. Environ. Med, 2000;10:267–9.

[4] Nicolson GL. Chronic infections as a common etiology for many patients with Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. Intern. J. Med, 1998;1:42–6.

[5] Nicolson GL, Nasralla M, Hier J, Erwin R, Nicolson NL. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel, 1999;4:172–6.

[6] Nicolson GL, Nasralla M, Franco AR, De Meirlier K, Nicolson NL, Ngwenya R, Haier J. Mycoplasmal infections in fatigue illnesses: Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis. J. Chronic Fatigue Syndr, 2000;6(3):23–39.

[7] Thornton D. A survey of mycoplasma detection in vaccines. Vaccine 1986;4:237–40.

[8] Nicolson, GL, Nasralla MY, Nicolson NL, Haier J. High prevalence of mycoplasmal infections in symptomatic (Chronic Fatigue Syndrome) family members of mycoplasma-positive Gulf War Illness patients. J. Chronic Fatigue Syndr, 2003;11(2):21-36.

[9] Nasralla M, Haier J, Nicolson GL. Multiple mycoplasmal infections detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. Eur. J. Clin. Microbiol. Infect. Dis, 1999;18:859–65.

[10] Nicolson GL, Nicolson NL. Diagnosis and treatment of mycoplasmal infections in Persian Gulf War Illness-CFIDS patients. Intern. J. Occup. Med. Immunol. Tox, 1996;5:69–78.

[11] Nicolson GL, Nicolson NL, Nasralla M. Mycoplasmal infections and Chronic Fatigue Illness (Gulf War Illness) associated with deployment to Operation Desert Storm. Intern. J. Med, 1998;1:80–92.

[12] Nasralla M, Haier J, Nicolson GL. Detection of mycoplasmal infections in blood of 565 chronic illness patients detected by polymerase chain reaction. Intern J. Med. Biol. Environ, 2000;28(1):15–23.

[13] Nicolson GL, Nasralla M, Haier J, Nicolson NL. Diagnosis and treatment of chronic mycoplasmal infections in Fibromyalgia and Chronic Fatigue Syndromes: relationship to Gulf War Illness. Biomed. Ther, 1998;16:266–71.

[14] Vojdani A, Franco AR. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis and Gulf War Illness. J. Chronic Fatigue Syndr, 1999;5:187–97.

[15] Nicolson GL, Nasralla M, Franco AR, Nicolson NL, Erwin R, Ngwenya R, Berns PA. Diagnosis and Integrative Treatment of Intracellular Bacterial Infections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness, Rheumatoid Arthritis and other Chronic Illnesses. Clin. Pract. Alt. Med, 2000; 1:92–102.

[16] Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CE. Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome. FEMS Immunol. Med. Microbiol, 1998;22:355–65.

[17] Nicolson GL, Berns P, Nasralla M, Haier J, Nicolson NL, Nass M. Gulf War Illnesses: chemical, radiological and biological exposures resulting in chronic fatiguing illnesses can be identified and treated. J. Chronic Fatigue Syndr. 2003; 11(1):21-36.

[18] Unwin C, Blatchley N, Coker W, Ferry S, Hotopf M, Hull L, et al. Health of UK servicemen who served in the Persian Gulf War. Lancet, 1999;353:169-178.

[19] Cherry N, Creed F, Silman A, Dunn G, Baxter G, Smedley J, et al. Health and exposures of United Kingdom Gulf war veterans. Part II: The relation of health to exposure. J. Occup. Environ. Med, 2001;58:299–306.

[20] Steele L. Prevalence and patterns of Gulf War Illness in Kansas veterans: association of symptoms with characteristics of person, place and time of military service. Amer. J. Epidemiol, 2000;152:992–1002.

[21] Mahan CM, Kang HK, Ishii EK. Anthrax vaccination and self-reported symptoms, functional status and medical conditions in the national health survey of Gulf War era veterans and their families. Presented to the Conference on Illnesses among Gulf War Veterans: A Decade of Scientific Research. Military and Veterans Health Coordinating Board, Research Working Group. Alexandria, VA: January 24-26, 2001.

[22] Nicolson GL, Nicolson NL. Gulf War Illnesses: complex medical, scientific and political paradox. Med. Conflict Surviv, 1998;14:74–83.

[23] Nicolson GL, Nass M, Nicolson NL. The anthrax vaccine controversy. Questions about its efficacy, safety and strategy. Med. Sentinel, 2000; 5:97–101.

DR. CHENEY: Balance the Immune System (Th1/Th2)

This is an old article (Kutapressin is no longer available in the US) but it does some great explaining so it’s a keeper.

By Carol Sieverling

Source : http://www.virtualhometown.com/dfwcfids/medical/nmh.html
DFW CFS and FM Support group : http://www.virtualhometown.com/dfwcfids/

This issue’s articles are based on tapes of Carol’s October 2000 visit. Dr. Cheney gave permission to share this information, but has not reviewed or edited it.

CFIDS patients are Th2 activated. This means they over-respond to toxins, allergens, normal bacteria and parasites, and under-respond to viruses, yeast, cancer and intracellular bacteria. Dr. Cheney suggests six products that can help rebalance the immune system.

Dr. Cheney explained that the immune system has two different modes of attack, based on the type of invader. One is Th1 (T Helper 1). It goes after organisms that get inside our cells ‚ intracellular pathogens. It is also known as cell-mediated immunity. The other is Th2 (T Helper 2). It attacks extracellular pathogens ‚ organisms that are found outside the cells in blood and other body fluids. Some call this humoral or antibody-mediated immunity. A healthy immune system is dynamic, able to switch back and forth as needed, quickly eradicating one threat and then resting before responding to the next.

(Dr. Cheney began this conversation by drawing a large inverted “V”. At the top point he wrote “Th0”, which he called “Th naught”. The left arrow pointed down to “Th1” and the right arrow to “Th2”. The arrow on the right was much darker and thicker, indicating that CFIDS patients are Th2 activated.)

Th0 are the naive, or unformed, cells of the immune system. They are resting, just waiting for an invader. When infection
occurs, they convert to either Th1 or Th2, depending on the type of threat. When the resting cell is exposed to a virus, cancer, yeast, or intracellular bacteria (like mycoplasma or chlamydia pneumonia), the Th1 response is initiated. (Dr. Cheney wrote these organisms beside the left arrow.) The weapons of the Th1 system include cytotoxic T cells and Natural Killer (NK) cells. (Cheney drew these below “Th1”.)

On the other side are normal bacteria, parasites, toxins, and allergens. (Likewise written beside the right arrow.) These trigger a predominately Th2 response. Its weapons include eosinophiles (Eos), polymononuclear cells (PMN), and antibody secreting cells (Ab). (Likewise written below “Th2”.)

How does the naive cell know which pathway to take? It depends on the cytokine information received. The presence of any organism from the left side triggers production of a cytokine called Interleukin 12. IL-12 causes the Th0 cell to move down the Th1 path. On the other hand, organisms on the right side trigger the production of Interleukin 10 (IL-10), which causes the Th0 cell to move down the Th2 path. (Cheney added small vertical dotted lines on each side, pointing upward to “IL-12” on the left and “IL-10” on the right. He then drew horizontal dotted arrows from “IL-12” and “IL-10”, each pointing inward toward the “Th0”, indicating that these cytokines determine whether it will become Th1 or Th2.)

Cheney said this is the point where it gets very interesting. Viruses, especially herpes viruses like EBV, CMV and HHV6, make proteins that mimic IL-10. The virus deceives the immune system into thinking that the threat is coming from the opposite side! So the immune system shifts from the Th1 mode that attacks viruses to the Th2 mode that does not. The virus increases its chances of survival by diverting the immune system. It is now thought that many, if not most, pathogens have this ability. (To represent this effect, Cheney drew a horizontal arrow about half way down the inverted “V”, originating from the left side and pointing toward, but not quite touching, the right side. The line was labeled “IL-10 like peptides”. Below it he drew a similar arrow from the right side that almost reached the left side. It was labeled “IL-12 like peptides”.)

Researchers have demonstrated that most CFIDS patients end up stuck in Th2 mode. This has several consequences. When the Th2 system activates, it blocks the Th1 system. This suppresses the Th1 weapons, particularly NK function. Accordingly, there is also an increase in the Th2 weapons – the white cells and antibodies. Most notable is increased antibody production. Dr. Cheney said that if you measure antibodies to anything a CFIDS patient has ever been exposed to, they will very likely be elevated. (At this point he drew small arrows beside the “weapons”: They pointed down on the left side to indicated suppression / lower levels; and they pointed up on the right side to indicate activation / higher levels.)

Cheney notes that other problems ensue. Patients get into trouble on both sides: they overreact to things on the right side and under-react to those on the left. When they are Th2 activated, they no longer have the defense mechanisms to keep dormant all the things they caught in the past. They cannot suppress or control them anymore, and the EBV, chlamydia pneumonia, CMV, etc. reactivate. The yeast also begins to appear.

The only defense against being eaten alive at this point is RNase L. (For more information about RNase L, see The Three Phases of CFIDS and other articles in the Cheney section of our website.) RNase L cannot kill any of these things. It only stops them from reproducing. According to Cheney, “It’s a line in the sand saying ‘No more replication’, and it waits for Th1 to come and kill them. But Th1 never comes. RNase L sits there and grinds away, possibly going up and down as the pathogens activate and reactivate. But they never get wiped out. RNase L holds the line, waiting for the cavalry that never arrives.”

While it is valiantly trying to hold the line, it is also chewing up human messenger RNA, inhibiting all the enzymes in the body, disrupting protein synthesis, and generally making patients miserable. As RNase L grinds away, it eventually shifts into “after-burner” desperation mode – the more powerful and deadly low molecular weight form discovered in CFIDS patients by Suhaldonik.

Cheney commented “RNase L is a very good anti-cancer defense. So as long as you’re involved in this scenario, you don’t get cancer. But a lack of growth hormone will wipe out RNase L, and we now know there is profound loss of growth hormone in CFIDS. Growth hormone is responsible for protein synthesis, and RNase L is a protein. So if you lose growth hormone, you lose protein synthesis, including RNase L. That may explain why, as the disease wears on and you get more injury, you stop seeing high levels of RNase L. You can’t make it anymore.”

He believes this is a very scary situation. Patients are Th2 activated and Th1 suppressed. The things on the left come out and there is nothing to stop them. There is no Th1, and eventually no Rnase L. He also believes patients need to balance the immune system – to push it a little more towards Th1. That way they will lose some of the overreaction on the right and gain some control on the left.

Cheney recommends the following to help shift the immune system from one mode to another. They are called “right to left shifters”. Three of them are published, or near publication.

1) Kutapressin (published, prescription)
Kutapressin is an immune modulator and a broad spectrum anti-viral. Dr. Cheney has found that it is most effective when the dose is varied or “pulsed”. The dose should vary from 1 to 4 cc daily; see the section on Isoprinosine for this theory. Dr. Cheney strongly suspects Ampligen is a right-to-left shifter also. He has said in the past that Kutapressin is rather like a weak form of Ampligen.

2) Isoprinosine (published, prescription)
Published for use in CFIDS, this anti-viral enhances NK function. Dr. Cheney believes it would also be good against intracellular bacteria since it is a Th2 – Th1 shifter. It appears to raise IL-12 and lower IL-10, which turns off Th2 and turns on Th1.

It is also called Imunovir and is very nontoxic, very safe. It has been approved in Europe and Canada for just about any viral infection for 18 years. It is not approved in the US (for political reasons, not safety concerns) but is easy to get from Ireland with a prescription. Contact Newport Pharmaceuticals at 353-1-890-3011, fax them at 353-1-890-3016 or email them at info@newport-pharma.comThis e-mail address is being protected from spam bots, you need JavaScript enabled to view it

Week one, take 6 tablets a day, Monday through Friday, and none on the weekend. Week two, take 2 tablets a day, Monday through Friday, and none on the weekend. Repeat this cycle. But do not treat every month. Do two months on and then one month off of this “pulsing” dose. This medicine works best when you do not treat regularly. If you treat continuously at the same dose, it stops working. It is an immune modulator, and Dr. Cheney suspects all immuno-modulators are like this. If taken continuously they stop working. The dose must vary so the immune system never knows what to expect.

3) Pine Cone Extract (supplement, http://www.pinextra.com)
Cheney said, “They make a tea from this in Southern Japan and they have significantly reduced cancer rates. It’s thought to work at the gene level in lymphocytes, where it turns on IL-12. It also shuts down IL-10 at the gene level, and that causes a shift towards Th1. Pine Cone extract is expensive, but at just 10 drops a day (in the morning), of all the possibilities, it’s probably the cheapest per day.” It is called PineExtra, and 1 oz is about $60, but it lasts a long time.

4) Earth Dragon Peptides (supplement, http://www.nutricology.com, http://www.needs.com)
Earth Dragon is round worm peptides. It causes a shift to the left, and is believed to be very similar to IL-12. There has been a huge surge in the use of ED peptides to treat Inflammatory Bowel Disease, specifically Crohn’s Disease. One professor at UNC treats all his Crohn’s Disease patients with Earth Dragon. It is very non-toxic and safe. This is a good choice for those who want to balance their immune system and also have bowel problems. Earth Dragon is about $36 for 150 caps. The dose is two a day.

5) Heparin (prescription)
Heparin is a Th2 – Th1 shifter. One advantage for many patients is that it is also an anticoagulant. Dr. Cheney only recommends this if a patient has a coagulopathy. About half of his patients do, according to the ISAC test. (See http://www.hemex.com or “Blood Related Disorders in CFS/FM.”)

6) Formula 560 Transfer Factor (to be published, supplement, http://www.immunitytoday.com)
Formula 560 is an immune modulator. Dr. Cheney likes this product. It reportedly works against HHV6 and Lyme Disease, as well as other problems. It costs about $585 for the first three months, then the dose drops one-third. It averages out to about $130 a month for the first six months, and $65 thereafter. (The cost of this product has reported dropped since this was first published.)
NOTE: Pro Health is an additional source for the Transfer Factor products (we carry the Formula 560 as well as the exact same product and from the same manufacturer that we call Transfer Factor 6000 and sell it for less).

Which should you use? Cheney recommends that you pick one and see what it does to your NK function. It is a question of whether it will work and how much it costs. NK levels will rise if there is a shift from Th2 towards Th1. Before beginning one of these products it is best to get a baseline on NK function. Then test again after having been on the product for one to three months. Dr. Cheney uses the lab of Mary Ann Fletcher, an NK specialist and colleague of renowned researcher Nancy Klimas, at the University of Miami. Her lab is no more expensive than commercial labs, and is top quality. Cheney emphasizes that you must have a quality lab do this test: do not use just any lab. For test information, phone 305-243-6288 or fax 305-243-4674. The test is called “Natural Killer Cell Function Assay” and costs $350.

Laten herpes virus infection in human trigeminal ganglia causes chronic immune response

Am J Pathol. 2003 Dec;163(6):2179-84.

Latent herpesvirus infection in human trigeminal ganglia causes chronic
immune response.

Theil D, Derfuss T, Paripovic I, Herberger S, Meinl E, Schueler O,
Strupp M, Arbusow V, Brandt T. Department of Neurology, Klinikum
Grosshadern, Ludwig-Maximilians University, Munich, Germany.
dtheil@brain.nefo.med.uni-muenchen.de

The majority of trigeminal ganglia (TGs) are latently infected with
alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and
varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the
TGs, VZV reactivates very rarely. The goal of this study was to determine
whether herpesvirus latency is linked to a local immune cell infiltration in
human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive
macrophages were found in 30 of 42 examined TGs from 21 healthy individuals.
The presence of immune cells correlated constantly with the occurrence of
the HSV-1 latency-associated transcript (LAT) and only irregularly with the
presence of latent VZV protein. In contrast, uninfected TGs showed no immune
cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma,
tumor necrosis factor-alpha, IP-10, and RANTES transcripts were
significantly induced in TGs latently infected with HSV-1 but not in
uninfected TGs. The persisting lymphocytic cell infiltration and the
elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for
the first time that latent herpesviral infection in humans is accompanied by
a chronic inflammatory process at an immunoprivileged site but without any
neuronal destruction. The chronic immune response seems to maintain viral
latency and influence viral reactivation.

Publication Types:
* Research Support, Non-U.S. Gov’t
PMID: 14633592 [PubMed – indexed for MEDLINE]

12: J Immunol. 1996 Oct 15;157(8):3542-9.

Persistent cytokine expression in trigeminal ganglion latently infected
with herpes simplex virus type 1.

Halford WP, Gebhardt BM, Carr DJ. Department of Microbiology,
Louisiana State University Medical Center, New Orleans 70112, USA.

Following ocular infection, herpes simplex virus type 1 (HSV-1)
establishes latency in trigeminal ganglion (TG) neurons. Using reverse
transcription-PCR, cytokine gene expression was analyzed in the TGs of mice
infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs
were readily detected in TGs taken from mice 7 days postinoculation (PI).
Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detected by ELISA of
TG homogenates. Between 5 and 45 days PI, IL-10, IFN-gamma, TNF-alpha, and
RANTES mRNAs were detected in nearly 100% of latently infected TGs (latent
infection was confirmed by reverse transcription-PCR detection of HSV-1
latency-associated transcripts). T cell-associated cytokine and chemokine
mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the
majority of latently infected TG samples taken between 60 and 135 days PI.
In contrast, these cytokine mRNA species were rarely detected in uninfected
TGs. Measurement of serum Abs to HSV-1 at different times revealed that
anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but
remained at high levels 67 and 125 days PI. Although there was molecular
evidence of an ongoing immune response to HSV-1 in latently infected TG,
histologic analysis indicated that very few mononuclear cells remained in
the ganglion 60 days PI. Collectively, the results suggest that residual
lymphocytes encounter viral Ag during HSV-1 latency with sufficient
frequency to remain activated. The paradox of a persistent immune response
against a latent infection is discussed.
Publication Types: PMID: 8871654

Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance

Click the title to link to the full study.

1: Egypt J Immunol. 2006;13(1):99-104.

*Possible immunological disorders in autism: concomitant
autoimmunity and immune tolerance.*

Kawashti MI, Amin OR, Rowehy NG.
Microbiology Department, Faculty of Medicine (For Girls), Al Azhar
University, Cairo, Egypt.

Autism is a pervasive developmental disorder that affect children
early in their life. Immunological disorders is one of several
contributing factors that have been suggested to cause autism.
Thirty autistic children aged 3-6 years and thirty non-autistic
psychologically-free siblings were studied. Circulating IgA and IgG
autoantibodies to casein and gluten dietary proteins were detected
by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles,
mumps and rubella vaccine (M.M.R) and cytomeglovirus were
investigated by EIA. Results revealed high seropositivity for
autoantibodies to casein and gluten: 83.3% and 50% respectively in
autistic children as compared to 10% and 6.7% positivity in the
control group. Surprisingly, circulating anti-measles, anti-mumps
and anti-rubella IgG were positive in only 50%, 73.3% and 53.3%
respectively as compared to 100% positivity in the control group.
Anti-CMV IgG was positive in 43.3% of the autistic children as
compared to 7% in the control group. It is concluded that,
autoimmune response to dietary proteins and deficient immune
response to measles, mumps and rubella vaccine antigens might be
associated with autism, as a leading cause or a resulting event.
Further research is needed to confirm these findings.

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