Familial Aggregation and Segregation Analysis in Families Presenting Autoimmunity, Polyautoimmunity, and Multiple Autoimmune Syndrome

Abstract

Studies documenting increased risk of developing autoimmune diseases (ADs) have shown that these conditions share several immunogenetic mechanisms (i.e., the autoimmune tautology). This report explored familial aggregation and segregation of AD, polyautoimmunity, and multiple autoimmune syndrome (MAS) in 210 families. Familial aggregation was examined for first-degree relatives. Segregation analysis was implemented as in S.A.G.E. release 6.3. Data showed differences between late- and early-onset families regarding their age, age of onset, and sex. Familial aggregation of AD in late- and early-onset families was observed. For polyautoimmunity as a trait, only aggregation was observed between sibling pairs in late-onset families. No aggregation was observed for MAS. Segregation analyses for AD suggested major gene(s) with no clear discernible classical known Mendelian transmission in late-onset families, while for polyautoimmunity and MAS no model was implied. Data suggest that polyautoimmunity and MAS are not independent traits and that gender, age, and age of onset are interrelated factors influencing autoimmunity.

Autoimmune Haemolytic Anaemia and Multiple Autoimmune Syndrome

“…It has been suggested, but not definitely demonstrated, that different infectious, genetic, immunological and even psychological factors can trigger MAS: genetic susceptibility and environmental triggers may interact to cause the condition. The predominant role of immunological responses is supported by a report that autoantibodies affect multiple organs in MAS [6] . The case described here is a typical form of MAS type III caused by three autoimmune disorders including hypothyroidism, Addison’s disease and AIHA.…”

Familial autoimmunity in pediatric patients with type 1 diabetes (T1D) and its associations with the severity of clinical presentation at diabetes diagnosis and with coexisting autoimmunity

“…There are very few studies to date assessing the frequencies of familial autoimmune diseases in the relatives of children and adolescents with T1D, and, to our knowledge, only one of them has reported on its association with the presence and severity of DKA at diagnosis of diabetes or pancreatic autoimmunity [12]. Several common genetic loci along with environmental factors can predispose to the manifestation of either a specific type or a spectrum of autoimmune diseases within the members of the family [13]. T1D is an excellent example of an autoimmune disease that is linked to other autoimmune diseases, either in the proband or in the family members.…”

Polyglandular Autoimmune Syndrome Associated with Multiple Autoimmune Conditions and Atopic Drmatitis - an Unusual Manifestation of a Polyautoimmunity Phenotype

“…This complex case can be classified both as PAS type III or IV, and as MAS type 3 and is highly illustrative for the concept of polyautoimmunity, which sets in relation diverse autoimmune conditions and diverse disease phenotypes with a common genotypic background (3,11,12). The coexistence of 4 autoimmune disorders has been documented in less than 25% of MAS patients(3), with SLE, AITD and vitiligo occurring the most frequently in different combinations (3,(12)(13)(14)(15). However, the coexistence of the particular four autoimmune diseases of our patient is rare.…”