Background/Purpose: Natural IgM autoantibodies have been proposed to have protective properties, and decreased levels of IgM to phosphorylcholine (PC) in SLE are associated with higher risk of atherosclerotic plaques and cardiovascular events. In the current study we investigated levels of total IgM and IgM anti-PC levels in different SLE subgroups.

Methods: Serum IgM levels were compared in 322 population controls and 351 SLE patients meeting ACR criteria. SLE patients were subgrouped based on antibody profiles into antiphospholipid (APS)-like (n=54, with ≥2 positive tests among anti-CL/β₂GPI; LA), Sjögren’s syndrome (SS)-like (n= 63, with ≥2 positive tests among anti-Ro52/Ro60/SSB), or SLE only with no “secondary syndrome” (n=234). A majority, but not all, of the APS-like and SS-like fulfilled clinical criteria for antiphospholipid syndrome or Sjögren’s syndrome. Total IgM levels were determined in the clinical laboratory, and IgM anti-PC measured using PC-BSA by sandwich ELISA. Analyses used the 2-sided Mann-Whitney test or Spearman correlation.

Results: IgM anti-PC levels were moderately but significantly decreased in the SLE patients (41.3±45.3 RU/ml) compared to matched controls (48.9±43.15 RU/ml) (n=316, p=0.002). Similarly, the total IgM levels were only slightly lower in SLE than controls (n=310, 1.22±1.1; 1.26±0.68 mg/ml, p=0.0002). There was a weak inverse correlation with age and disease duration for IgM anti-PC (p=0.02, R=-0.13; p=0.0003, R=-0.19). Importantly, APS-like patients did not have significantly altered total IgM (1.51±1.1 mg/ml) or IgM anti-PC levels (58.7±58.7 RU/ml) compared to controls (IgM 1.26±0.7 mg/ml; IgM anti-PC 48.7±43.2 RU/ml), while the SLE only group had moderately decreased IgM levels (IgM 1.21±1.3 mg/ml, p<0.0001; IgM anti-PC 39.5±43.0 RU/ml; p=0.002), and the SS-like patients had considerably impaired IgM (IgM 0.96±0.6 mg/ml, p<0.0001; IgM anti-PC 23.4±24.2 RU/ml, p<0.0001). There were no statistically significant differences based on age, disease duration, female sex, or anti-dsDNA positivity. In all SLE patients, total IgG levels were significantly increased compared to controls, and were highest in the SS-like group.

Conclusion: Alterations in IgM levels between SLE subgroups further emphasize the immune heterogeneity of patients diagnosed with SLE. Patients have different clinical manifestations, risk of co-morbidities, and which also have distinct immunological features. Future studies are needed to investigate the clinical relevance of depressed IgM levels, and if the moderate IgM impairment in certain SLE patients reflects underlying immunological differences and/or is due to consumption of natural IgM or others causes resulting in skewing of the B-cell repertoire.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depressed-serum-igm-levels-in-sle-are-restricted-to-defined-subgroups/