Depressed serum IgM levels in SLE are restricted to defined subgroups

TL;DR

This study reveals that specific subgroups of SLE patients exhibit depressed serum IgM levels, linked to distinct autoantibody profiles and genetic factors, which may influence disease mechanisms and clinical outcomes.

Contribution

It identifies subgroup-specific IgM depression in SLE and associates it with autoantibody profiles and genetic variants, providing new insights into disease heterogeneity.

Findings

Depressed IgM levels are more common in SLE than controls.

IgG anti-Ro/La profile correlates with reduced IgM anti-PC and MDA.

Low IgM anti-PC associates with cardiovascular disease in certain SLE subgroups.

Abstract

Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/Beta2glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant amongst SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.