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

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.