It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.

Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder.

Background: Helminthic infections induce an IL-4–dependent polyclonal stimulation of IgE synthetization. It is still unclear, however, what role helminths play in allergic sensitization. Objective: We sought to determine the relationship between Ascaris -specific IgE and allergic sensitization in a nontropical country. Methods: In 2 consecutive cross-sectional surveys in 1992-1993 and 1995-1996, data from school entrants (age range, 5 to 7 years), third graders (age range, 8 to 10 years), and sixth graders (age range, 11 to 14 years) were collected. The 2 younger groups were reexamined in the second survey. Data for about 2300 children, including a cohort of 700 subjects, were analyzed. Ascaris IgE and total and specific IgE to inhalant allergens were measured, and skin prick tests were performed. Information about asthma and allergic rhinitis was collected by a questionnaire. Results: Children who were Ascaris -IgE seropositive (>0.35 IU/mL) in both surveys had 10-fold higher levels of total IgE (451 IU/mL vs 45 IU/mL, P P P P Ascaris -seronegative in the first survey but seropositive in the second survey, total and specific IgE increased markedly. Sensitization to Dermatophagoides pteronyssinus increased nearly 3-fold in this group. In contrast, in children who became Ascaris -seronegative, total and specific IgE decreased. Conclusions: Contact with low doses of helminthic antigen is associated with an increase of total and specific IgE production. Helminthic infections in East German children are not the cause for a low prevalence of allergies in the former East Germany. (J Allergy Clin Immunol 1998;102:414-20.)

Ascaris-specific IgE and allergic sensitization in a cohort of school children in the former East Germany

This review assesses the current state of knowledge regarding the cecal appendix, its apparent function, and its evolution. The association of the cecal appendix with substantial amounts of immune tissue has long been taken as an indicator that the appendix may have some immune function. Recently, an improved understanding of the interactions between the normal gut flora and the immune system has led to the identification of the appendix as an apparent safe-house for normal gut bacteria. Further, a variety of observations related to the evolution and morphology of the appendix, including the identification of the structure as a "recurrent trait" in some clades, the presence of appendix-like structures in monotremes and some non-mammalian species, and consistent features of the cecal appendix such as its narrow diameter, provide direct support for an important function of the appendix. This bacterial safe-house, which is likely important in the event of diarrheal illness, is presumably of minimal importance to humans living with abundant nutritional resources, modern medicine and modern hygiene practices that include clean drinking water. Consistent with this idea, epidemiologic studies demonstrate that diarrheal illness is indeed a major source of selection pressure in developing countries but not in developed countries, whereas appendicitis shows the opposite trend, being associated with modern hygiene and medicine. The cecal appendix may thus be viewed as a part of the immune system that, like those immune compartments that cause allergy, is vital to life in a "natural" environment, but which is poorly suited to post-industrialized societies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ar.21357

The cecal appendix: one more immune component with a function disturbed by post-industrial culture.

Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases.

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-3083.2006.01785.x

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis.

Electrophoresis: cellulose acetate vs agarose gel, visual inspection vs densitometry.

Serum IgE determinations and coproparasitological analyses were carried out on 161 individuals from two distinct ethnic groups (Hutus and Twas) from two regions in Rwanda (North and South). The cumula

Relationship between Serum IgE Levels and Intestinal Parasite Load in African Populations

Serum IgE levels and IgE antibodies against four intestinal parasites, and the presence and abundance of parasites in stool samples were investigated in 161 Rwanda natives. Most of the IgE turn out to be helminth-reacting antibodies. The stimulation and production of these antibodies are much different from those of anti-amoeba antibodies in their relation to the specific intestinal parasite load; helminth infestations seem to play a major role in the development of anti-amoeba antibodies as well.

Parasite-Reactive Serum IgE Antibodies in African Populations. Relation to Intestinal Parasite Load

Data on serum protein levels in Binga Pygmies are presented, and these are compared with the levels in healthy Italians and in Italians suffering from liver diseases. Principal Component Analysis carried out on the three groups points out similarities in protein levels between the Pygmies and the Italian Hepatopaths on one hand and between healthy and liver diseased Italians on the other. Discriminant Analyses reveal the important differences between the populations. It is suggested that such analyses of protein levels could serve as tools in population biology.

Serum protein levels as anthropological markers: a statistical analysis in Binga Pygmies and Italians.

Serum protein analysis by molecular interpretation of cellulose acetate electrophoresis: evaluation of its clinical usefulness

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