Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis

Abstract

Objective. To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects.Methods. Interviews were used to obtain histories of the following disorders among living first-and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulindependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chisquares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently.Results. There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in firstdegree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P ‫؍‬ 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families.Conclusion. These data demonstrate that the prevalence of autoimmunity is significantly higher among first-and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.

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

“…We did not find associations with any other specific autoimmune disorders, but even with an estimated 3100 total relatives in this study, we may not have had sufficient power to detect differences in the less common autoimmune disorders. The reports of an increased prevalence of AITD and other immune disorders among relatives of patients with rheumatoid arthritis (Walker, Griffiths, & Griffiths, 1986), Type I Diabetes (Payami, Joe, & Thomson, 1989), idiopathic inflammatory myopathy (Ginn et al, 1998), multiple sclerosis (Broadley, Deans Sawcer, Clayton, & Compston, 2000) and JRA (Prahalad, Shear, Thompson, Giannini, & Glass, 2002) have been interpreted as evidence for a common polygenic risk factor that confers susceptibility to autoimmunity (Ginn et al, 1998).…”

Familial autoimmunity: maternal parent-of-origin effect in juvenile idiopathic arthritis

“…A complete description of methods for the case-control study has been published [2]. In summary, structured interviews were conducted to obtain histories of AI diseases among living first and second-degree relatives among 110 simplex and 23 multiplex JIA families, as well as 45 control families.…”

“…An increased prevalence of autoimmune (AI) diseases among relatives of probands with JIA patients has been demonstrated [2]. The prevalence of AI diseases is also increased among relatives of probands with inflammatory myopathies or rheumatoid arthritis (RA) [3,4].…”

“…Other factors that could complicate genetic studies include parent-oforigin effects, wherein the gender of the disease transmitting parent could influence the expression of disease in offspring. The objective of the present study was to determine if there is a parent-of-origin effect in JIA, utilizing data obtained in our previous case-control study [2].…”

Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions

“…The HLA association and some of the other susceptibility genes for RA are shared by some other autoimmune diseases (4). Even family studies have noted clustering of other autoimmune diseases in families of RA patients (2,(7)(8)(9)(10)(11).…”