First-degree relatives of patients with systemic lupus erythematosus: Autoreactivity but not autoimmunity?

Abstract

Background: Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first-degree relatives (FDRs) constitute a group at elevated risk. The current understanding is that external risk factors trigger underlying immune dysregulations, leading to overt disease in those with elevated genetic risk.

Objective: This cross-sectional study investigates the degree to which clinical features, external risk factors, and immunological profiles differ in SLE FDRs from healthy individuals and SLE patientts.

Methods: Three groups were studied: Lupus patient FDRs (n = 56), healthy controls (n = 20), and SLE patients (n = 20). FDRs and healthy participants completed a detailed clinical questionnaire that included questions regarding smoking and estrogen drug history. All participants were tested for the presence of the following antinuclear autoantibodies (ANAs) against: nRNP/Sm, Sm, Ro60, Ro-52, La, Scl-70, PM-Scl, PM- Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosomes, histones, RibP, AMA M2, DFS70, and eight soluble cytokines, including transforming growth factor-β (TGF-β), vitamin D levels, and antibodies against Epstein-Barr virus (EBV).

Results: Compared with the healthy controls, FDRs had higher titers of ANA, more specific staining immunofluorescent patterns, and more autoantibody specificities. Furthermore, FDRs differed significantly in their TGF-β levels from the other two groups. In FDRs, some clinical features (hair loss, skin, and oral ulcer-like lesions) were associated with higher ANA titers and some (oral ulcer-like lesions) with the anti-Ro60-specific antibody. Interestingly, there was an association between ANA titers and levels of antibodies against EBV only in the FDR group.

Conclusion: First-degree relatives display unique clinical and immunological profiles, placing them between healthy individuals and SLE patients, with a balance between compensated immune dysregulation and disease-developing potential. A possible association between ANA titer and the number of clinical complaints is observed, which needs to be confirmed in more extensive studies.

Keywords: antinuclear antibodies; antinuclear antibody patterns; autoimmunity; first-degree relatives; systemic lupus erythematosus; transforming growth factor-β.