Familial Aggregation of Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Other Autoimmune Diseases in 1,177 Lupus Patients from the GLADEL Cohort

Objective: To determine whether there is familial aggregation of systemic lupus erythematosus (SLE) and/or other autoimmune diseases in SLE patients and to identify clinical differences between patients with and those without familial autoimmunity.

Methods: We interviewed members of the Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL) inception cohort of 1,214 SLE patients to ascertain whether they had relatives with SLE and/or other autoimmune diseases. Identified relatives were studied. Familial aggregation was tested using reported highest and intermediate population prevalence data for SLE, rheumatoid arthritis (RA), or all autoimmune diseases, and studies were performed to identify the genetic model applicable for SLE.

Results: We identified 116 first-, second-, or third-degree relatives with SLE, 79 with RA, 23 with autoimmune thyroiditis, 3 with scleroderma, 1 with polymyositis, and 16 with other autoimmune diseases, related to 166 of the 1,177 SLE patients in the GLADEL cohort who agreed to participate. Forty-two SLE patients had 2 or more relatives with an autoimmune disease. We found a lambda(sibling) of 5.8 and 29.0 for SLE and of 3.2-5.3 for RA, when comparing with their reported high or intermediate population prevalence, respectively. We also found familial aggregation for autoimmune disease in general (lambda(sibling) = 1.5) and determined that for SLE, a polygenic additive genetic model, rather than a multiplicative one, is applicable.

Conclusion: In SLE there is familial aggregation of SLE, RA, and autoimmune disease in general. A polygenic additive model applies for SLE. American Indian-white Mestizo SLE patients and those with higher socioeconomic level were more likely to have familial autoimmunity.