Autoimmune Disorders in Probands and First-Degree Relatives of the Simons Simplex Collection Data

Background: Hypotheses have been raised about an autoimmune model of autism. Some epidemiological data suggest increased rates of autoimmune disorders in first-degree relatives of subjects with autism spectrum disorders (ASD). Regression in ASD has also been postulated to reflect autoimmune dysfunction.

Objectives: To evaluate the lifetime prevalence of autoimmune disorders in ASD probands and in their first-degree relatives, and to compare it to that in the general population; 2. To determine if phenotypic differences in the ASD probands were associated with the presence or absence of autoimmune disorders in either the proband or his/her first-degree relatives.

Methods: The sample consisted of 414 probands (mean age: 9.5 years; SD = 3.2 – 86.7% male) with ASD (65.7% Autistic Disorder; 21.7% PDD-NOS; 12.6% Asperger’s Disorder) collected as part of the Simons Foundation funded genetic study of simplex families. Data regarding the lifetime occurrence of 14 specific autoimmune disorders were collected for the proband, parents, full siblings, and other more distant relatives. Probands had a state-of-the-art research diagnostic evaluation.

Results: Thirty-nine probands (9.4%) had an autoimmune disorder (asthma: 7.0%; lupus: .2%; hypothyroidism: .2%; psoriasis: .5%; celiac disease: .2%; other: .5%). Comparisons of the probands with (N = 39) or without (N = 375) any autoimmune disorder showed no statistical difference for diagnosis, age of recognition of first symptoms, age of first single words or of phrase speech, presence/absence of regression, scores for ADI-R and ADOS, standard scores for IQ and Peabody Picture Vocabulary Test (PPVT), standard scores for the Vineland Adaptive Behavior Scale – Second Edition (VABS-II), Repetitive Behavior Scale Revised (RBS-R) mean factor and total scores, Aberrant Behavior Checklist (ABC) factor scores, and Child Behavior Checklist (CBCL) internalizing, externalizing and total T-scores. There were 163 (39.4%) first-degree relatives with at least one autoimmune disorder (juvenile rheumatoid arthritis: .5%; adult rheumatoid arthritis: 1.9%; lupus: .2%; asthma: 19.8%; hyperthyroidism: 1.4%; hypothyroidism: 4.8%; Hashimoto disease: 1.2%; diabetes Type I: 1.0%; diabetes Type II: 3.6%; psoriasis: 4.8%; celiac disease: .5%; inflammatory bowel disorder: 5.6%; multiple sclerosis: .2%; other: 3.1%). Comparisons of the subgroup of probands with first-degree relatives with (N = 163) or without (N = 251) any autoimmune disorder showed no statistical difference for diagnosis, age of recognition of first symptoms, age of first single words or of phrase speech, presence/absence of regression, standard scores for IQ, VABS-II, PPVT, the RBS-R mean factor and total scores, the ABC factor scores, and the CBCL internalizing, externalizing and total T-scores. Significant differences were found for the social and repetitive ADI-R subscores, and for the socio-communicative and repetitive ADOS scores. These differences were of small magnitude, and were inconsistent in direction and across measures. Comparisons of prevalence rates of autoimmune disorders in this sample with known epidemiological estimates will be presented at the conference.

Conclusions: In cases of ASD that occur sporadically, the presence of autoimmune disorders in the proband or in first-degree relatives was not associated with identifiable variations of the phenotype. Additional studies on autism multiplex families could further evaluate the possible association between autoimmune disorders and ASD.