  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.
