Prelim. Study - Suggested impaired immune tolerance for some

[Lara]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16996487&query_hl=1&itool=pubmed_docsum
Biol Psychiatry. 2007 Feb 1;61(3):273-8. Epub 2006 Sep 25.

Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study.

* Kawikova I,
* Leckman JF,
* Kronig H,
* Katsovich L,
* Bessen DE,
* Ghebremichael M,
* Bothwell AL.

Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.

BACKGROUND: Post-streptococcal autoimmune inflammation of basal ganglia was suggested to be an etiological factor in some cases of Tourette syndrome (TS). Since regulatory T (T reg) cells play a major role in preventing autoimmunity, we hypothesized that a defect in T reg cells may be present in children with TS. We also postulated that group A beta hemolytic streptococcal infections could promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic exotoxins [SPE]).

METHODS: We analyzed peripheral blood of TS patients and healthy age-matched control subjects by fluorescence-activated cell sorting (FACS) on multiple occasions and determined the numbers of CD4(+)CD25(+)CD69(-) T reg cells. Further, we quantified the number of CD4(+) and CD8(+) lymphocytes with regard to Vbeta chains to which SPEs are known to bind.

RESULTS: A significant decrease in T reg cells was observed in patients with moderate to severe TS symptoms compared with healthy age-matched control children. A decrease in T reg cell number was also noted during symptom exacerbations in five out of six patients. Further, we found a significant decrease in numbers of CD8(+)Vbeta18(+) T cells in moderate to severe TS patients.

CONCLUSIONS: These data support our hypothesis that at least some TS patients may have a decreased capacity to inhibit autoreactive lymphocytes through a deficit in T reg cells. Interactions of host T cell immunity and microbial factors may also contribute to the pathogenesis of TS.

PMID: 16996487 [PubMed - indexed for MEDLINE]

doi:10.1016/j.biopsych.2006.06.012

[Chemar]

that is very interesting Lara

my son has never had strep, but he does have Crohn's Disease, which is autoimmune

[Lara]

I'm excited!!!

I think it's one of the most interesting things to see Yale come out with this after all these years. Some pieces are in the zigsaw are fitting together. I'm totally excited to read this extract. Hoping to hunt down the rest of it as soon as possible.

Edited to add: I guess I should clarify what I mean by being excited and why it's so interesting to me. It's because of my son's history, not my daughter's though. He had a totally different background medical history which included early diagnosis of Sydenham's Chorea (after suspected Rheumatic Fever) and some other things including later diagnosis of ASD. When I say interesting from Yale, I mean immune related. The outcome isn't going to make any difference to how my children are doing now, but it *may* answer a few of my questions I still have about a lot of things that have happened to him.

[Laurensmom]

Thanks for sharing.

[Laurensmom]

My daughter has TS and my husband is type 1 diabetic, so this is very interesting:

Regulatory T cells (also known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self. The existence of a dedicated population of "suppressor" T cells was the subject of significant controversy among immunologists for many years. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their critical role in the vertebrate immune system. Interest in regulatory T cells has been heightened by evidence from experimental mouse models demonstrating that the immunosuppressive potential of these cells can be harnessed therapeutically to treat autoimmune diseases and facilitate transplantation tolerance or specifically eliminated to potentiate cancer immunotherapy.

......

To function properly, the immune system must discriminate between self and non-self. When self/non-self discrimination fails, the immune system destroys cells and tissues of the body and as a result causes autoimmune diseases. Regulatory T cells actively suppress activation of the immune system and prevent pathological self-reactivity, i.e. autoimmune disease. The critical role regulatory T cells play within the immune system is evidenced by the severe autoimmune syndrome that results from a genetic deficiency in regulatory T cells.

......

The molecular mechanism by which regulatory T cells exert their suppressor/regulatory activity has not been definitively characterized and is the subject of intense research. In vitro experiments suggest that suppressive mechanism requires cell-to-cell contact with the cell being suppressed. However, the immunosuppressive cytokines TGF-beta and Interleukin 10 (IL-10), produced by Th3 and Tr1 cells respectively, have also been implicated in regulatory T cell function.

An important question in the field of immunology is how the immunosuppressive activity of regulatory T cells is modulated during the course of an ongoing immune response. While the immunosuppressive function of regulatory T cells prevents the development of autoimmune disease, it is not desirable during immune responses to infectious microorganisms. Current hypotheses suggest that upon encounter with infectious microorganisms the activity of regulatory T cells may be downregulated, either directly or indirectly, by other cells to facilitate elimination of the infection. Experimental evidence from mouse models suggests that some pathogens may have evolved to manipulate regulatory T cells to immunosuppress the host and so potentiate their own survival. For example, regulatory T cell activity has been reported to increase in several infectious contexts, such as retroviral infections and various parasitic infections including Leishmania and malaria.

http://en.wikipedia.org/wiki/Regulatory_T_cell

[Tessa]

Lara,

This is very exciting!!! It is encouraging that they are looking at these issues, as well. I do think it is a key puzzle piece for many, too. I thought Yale had pooh-poohed the strep connection.

Thanks for posting this. Reminds me of the old board and our discussions about this with dkw (aka) and FJ. I hope they are well.

Take care,
Tessa

[Chemar]

Lara,

Thanks for posting this. Reminds me of the old board and our discussions about this with dkw (aka) and FJ. I hope they are well.

Take care,
Tessa

:) it would be great to see FJ* and dkw/aka here Tessa:p

FJ* has helped so many people recognise and treat for pyroluria and dkw has a wealth of knowledge and experience on so many of these deep rooted areas of understanding the ASDs

I get really hopeful when I see how much new research and information is coming out to validate what so many have referenced anecdotally.

Tessa, did you notice the article in Discover Magazine re autism...that in itself was a breath of fresh air in the way autism tends to be portrayed in the media
http://discovermagazine.com/2007/apr/autism-it2019s-not-just-in-the-head/article_view?b_start:int=0&-C=

[Lara]

I was thinking about aka when I read and posted that article as well.

G'day to Laurensmom! :Wave-Hello:

[Lara]

Am J Med Genet B Neuropsychiatr Genet. 2007 May 14;

A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report.

Lit L, Gilbert DL, Walker W, Sharp FR.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17503477&query_hl=16&itool=pubmed_docsum

Gilles de la Tourette Syndrome (TS) is a heritable, neurodevelopmental disorder characterized by motor and vocal tics. As no single gene or region has emerged from standard linkage approaches, TS may result from several as-yet-unidentified genetic factors, and may also occur due to infection-triggered, autoimmune processes. Etiological or pathogenic differences might result in clinically indistinguishable TS subgroups. We have previously used whole genome human oligonucleotide microarrays in an attempt to identify patterns of gene expression in blood linked with TS. In this proof-of-principle study, we applied Principal Components Analysis to a previously collected set of 16 familial TS and 16 control blood samples to identify subgroups. Fourteen genes, primarily Natural Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and NKG7 were confirmed using RT-PCR. Five probesets (four genes) reside in chromosomal regions previously linked to familial TS or obsessive-compulsive disorder. Using the 14 genes, a Principal Components Analysis as well as a cluster analysis identified a TS subgroup (n = 10/16) that overexpressed the NK genes. 7/10 subjects within this subgroup were diagnosed with attention-deficit hyperactivity disorder (ADHD), suggesting that this expression profile might be associated with TS and co-morbid ADHD. Principal Components Analysis of gene expression in blood may be useful for identifying subgroups of other complex neurodevelopmental diseases, and the gene expression profile identified in this study may provide a biomarker for at least one subgroup of heritable TS. (c) 2007 Wiley-Liss, Inc.

PMID: 17503477

[Lara]

Mov Disord. 2007 May 21;
Antineuronal antibody status and phenotype analysis in Tourette's syndrome.
Martino D, Defazio G, Church AJ, Dale RC, Giovannoni G, Robertson MM, Orth M.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17516471&query_hl=1&itool=pubmed_docsum

The Gilles de la Tourette syndrome (GTS) spectrum includes psychiatric comorbidities, mainly obsessive-compulsive disorder (OCD) and attention-deficit-hyperactivity disorder (ADHD). The role of environmental factors, e.g., antineuronal antibodies (ANeA), remains unclear. We compared the clinical features of ANeA-positive and ANeA-negative patients in 53 children and 75 adults with GTS. All diagnoses were made according to DSM-IV-TR criteria. A positive ANeA Western immunoblot showed bands for at least 1 of 3 reported striatal antigens (40, 45, and 60 kDa). Twelve children (23%) and 18 adults (25%) with GTS were ANeA-positive. Disease duration, tic phenomenology and severity, frequency of echo/pali/coprophenomena, self-injurious and aggressive behavior, or frequency of OCD comorbidity did not significantly differ between ANeA-positive and negative patients. Similar findings were obtained analyzing separately the three different antibody reactivities. A comorbid diagnosis of ADHD was significantly less frequent in GTS patients positive for the anti-60 kDa antibody only. Using a multivariate logistic regression model, adjusting for age, gender, and age at disease onset, a comorbid diagnosis of ADHD remained inversely associated with anti-60 kDa antibodies (odds ratio = 0.14; P = 0.002; 95% confidence interval 0.04-0.49). ANeA status does not differentiate a specific phenotype of GTS. (c) 2007 Movement Disorder Society.

PMID: 17516471

[limpia]

fascinating- we have diabetes, crohns in family

[limpia]

Hi - I have read that there is a connection between diabetes , an autoimmune condition, and sleep apnea.

One-Third of Diabetics Have Sleep Apnea

MONDAY, July 30 (HealthDay News) -- People with type 2 diabetes who drag themselves through the day may be among the 36 percent of diabetics suffering from obstructive sleep apnea, according to new research.

Sleep apnea occurs when impaired breathing due to collapsed airways triggers multiple nighttime awakenings.

Researchers at The Whittier Institute for Diabetes in La Jolla, Calif., analyzed health data from 279 adults with type 2 diabetes. They found that one out of three diabetics also suffered from obstructive sleep apnea. Men, particularly those over the age of 62, were more than twice as likely as women to experience interrupted sleep.

Previous research has indicated a relationship between obstructive sleep apnea, glucose intolerance and insulin resistance, so the connection with type 2 diabetes is not surprising. This is the first study to analyze data from both men and women at a diabetes clinic, the researchers said.

"These findings demonstrate that obstructive sleep apnea has a high prevalence in adults with type 2 diabetes," principal investigator Dr. Daniel Einhorn said in a prepared statement. "Given that treatment of obstructive sleep apnea has the potential to both decrease blood pressure and improve glycemic [blood sugar] control, individuals with type 2 diabetes should be regularly screened for the presence of sleep apnea," he said.

The researchers published their findings in the current issue of Endocrine Practice.

According to previous research, treating people who have both obstructive sleep apnea and type 2 diabetes with "continuous positive airway pressure" therapy not only helps manage the sleep interruptions but also reduces blood sugar levels. The researchers recommend that clinicians screen patients with type 2 diabetes for obstructive sleep apnea.

According to the American Diabetes Association, more than 20 million people in the United States have diabetes, with more than one in five adults over the age of 60 suffering from the disease. Type 2 is the most common form of diabetes, a disease in which the body does not make or use insulin effectively.

The National Sleep Foundation estimates that more than 18 million people suffer from obstructive sleep apnea, although the majority of people have not been diagnosed with the disorder. Obstructive sleep apnea is related to a multitude of health risks, including heart disease, high blood pressure, depression, sexual dysfunction and an increased risk of car accidents.

-- Madeline Vann

SOURCE: The Whittier Institute for Diabetes, news release, July 30, 2