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

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

doi:10.1186/s10020-018-0019-4

Abstract

BackgroundSystemic 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.MethodsOur 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.ResultsThe 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.ConclusionThis risk index may be useful in early interventions to prevent SLE. In addition, it suggests new therapeutic approaches for the treatment of SLE.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences
Anti-dsDNA antibodies As IgM antibodies precede the generation of IgG antibodies and protect against SLE onset, we assessed IgM anti-DNA antibodies in all 5 cohorts (Fig. 1)
Titers were lowest in the SLE, SLE patients (SIS), and Healthy African American women (AAHC) cohorts

Summary

Introduction

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. West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by defects in B cell tolerance leading to the production of multiple autoantibodies. While the etiology SLE is not known, data suggest that susceptibility requires both a genetic predisposition and environmental triggers. Over 50 risk alleles for SLE have been identified and disease severity and age of onset relates, in part, to the number of risk alleles present in an individual (Teruel and Alarcon-Riquelme 2016).

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Results

Discussion

Conclusion