Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism

Abstract

Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis.

Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

“…Previous case-control studies have found familial autoimmunity to be a risk factor for autism (Comi et al, 1999;Sweeten et al, 2003). In our study we found that, in children diagnosed with ASD, a history of familial autoimmunity, specifically AITD is a significant risk factor for regression, suggesting that this group of children with ASD and regression may contribute substantially to the associations that have been described.…”

“…Elevated serum immunoglobulins (Croonenberghs et al, 2002b) and autoantibodies to neuronal elements (Singh, Warren, Averett, & Ghaziuddin, 1997) have also been reported in children with autism. In addition, Comi et al reported that 66% of children with autism had at least one relative with an autoimmune disorder, compared to 50% of normally developing controls (Comi, Zimmerman, Frye, Law, & Peeden, 1999). Sweeten and colleagues also reported a significantly higher mean number of autoimmune disorders in families of children with PDDs (1.87±1.6) compared to families of healthy controls (0.93±1.1) or children with known autoimmune disorders (1.44±1.5) (Sweeten, Bowyer, Posey, Halberstadt, & McDougle, 2003).…”

“…While there is evidence to support ASD as an autoimmune phenomenon which is commonly associated with a cell-mediated, T H 1 response (Comi, Zimmerman, Frye, Law, & Peeden, 1999;Singh, Warren, Averett, Ghaziuddin, 1997;Sweeten, Bowyer, Posey, Halberstadt, & McDougle, 2003) there is also evidence that the disorder is associated with an allergic (T H 2) immune response (Lucarelli, et al, 1995;Gupta, Aggarwal, Rashanravan, & Lee, 1998), or that ASD is associated with general dysregulation of the immune system (Gupta, Aggarwal & Heads, 1996;Jyonouchi, Sun, & Le, 2001). These conflicting results may be due in part to the underlying heterogeneity within ASD, a diagnosis based on observable clinical and historical findings.…”

Generalized Autoimmunity of ANCA and ASCA Related to Severity of Disease in Autistic Children with GI Disease

“…46 Separate epidemiologic studies suggest that a family history of autoimmune disorders is more common among children with autism than healthy control children. 38,39 There is also increased incidence of asthma, allergy, autoimmune psoriasis and Type I diabetes in mothers of children with ASD, 40 and first degree relatives of children with autism and Aspergers are more likely to have an autoimmune disease compared to controls. 41,42 While significantly higher levels of autoantibodies are detected in autistic patients when compared with controls, the pathophysiological significance of these antibodies is uncertain.…”

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

“…[35][36][37][38] Finally, an increased frequency of autoimmune disorders has been described in the families of individuals with autism. Comi et al 39 found a positive correlation between the risk of autism and the number of family members affected with an autoimmune disease, with the highest risk associated with maternal autoimmunity. Similarly, immune disorders such as asthma and allergies, as well as the autoimmune diseases diabetes and psoriasis, were increased in mothers of children with autism spectrum disorder (ASD).…”