IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE

Emerging evidence suggests that there are IgM-autoantibodies that may play protective roles in SLE. While IgM are often considered polyreactive, we postulate that there are distinct sets of IgM-autoantibodies of defined autoreactive specificities relevant to different features of SLE. We examined the relationships between levels of IgM natural autoantibodies (NAbs) to apoptosis-associated phosphorylcholine (PC) or malondialdehyde (MDA) antigens, with lupus-associated autoantibodies and features of disease, in 120 SLE patients. IgM anti-PC was significantly higher in patients with low disease activity and less organ damage determined by the SELENA-SLEDAI, the physician's evaluation and the SLICC damage score. Furthermore, IgM anti-PC was significantly higher in patients without cardiovascular events. In contrast, IgM anti-cardiolipin and IgM anti-dsDNA were significantly higher in patients without renal disease. These results support the hypothesis that some IgM autoantibodies are part of a natural immune repertoire that provide homeostatic functions and protection from certain clinical lupus features.

► IgM autoantibodies may play protective roles in SLE. ► Higher IgM anti-PC correlates with less active disease and organ damage. ► Higher IgM anti-PC correlates with lower CV events. ► Higher IgM anti-cardiolipin (CL) and anti-dsDNA correlate with no renal disease. ► IgM to PC, CL, β2-GPI, dsDNA correlate with protection from distinct SLE features.