Serologic features of cohorts with variable genetic risk for systemic lupus erythematosus

Jyotsna Bhattacharya, Karalyn Pappas, Bahtiyar Toz, Cynthia Aranow, Meggan Mackay, Peter K. Gregersen, Ogobara Doumbo, Abdel Kader Traore, Martin L. Lesser, Maureen McMahon, Tammy Utset, Earl Silverman, Deborah Levy, William J. McCune, Meenakshi Jolly, Daniel Wallace, Michael Weisman, Juanita Romero-Diaz, Betty Diamond

Systemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences. In Western Europe and North America, individuals of West African descent have a 3-4 fold greater incidence of SLE than Caucasians. Paradoxically, West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. In this study, we analyzed sera from African American female SLE patients and four other cohorts, one with SLE and others with varying degrees of risk for SLE in order to identify serologic factors that might correlate with risk of or protection against SLE. Our cohorts included West African women with previous malaria infection assumed to be protected from development of SLE, clinically unaffected sisters of SLE patients with high risk of developing SLE, healthy African American women with intermediate risk, healthy Caucasian women with low risk of developing SLE, and women with a diagnosis of SLE. We developed a lupus risk index (LRI) based on titers of IgM and IgG anti-double stranded DNA antibodies and levels of C1q. The risk index was highest in SLE patients; second highest in unaffected sisters of SLE patients; third highest in healthy African-American women and lowest in healthy Caucasian women and malaria-exposed West African women. This risk index may be useful in early interventions to prevent SLE. In addition, it suggests new therapeutic approaches for the treatment of SLE.