Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Protection from Cardiovascular Events and Nephritis in SLE Correlates with Levels of IgM Natural Autoantibodies to Different Apoptosis-Associated Antigens.
Gronwall3, Caroline, Akhter2, Ehtisham, Petri1, Michelle A., Silverman3, Gregg J.
In murine models, we have reported that induction of high levels of IgM antibodies to phosphorylcholine (PC), a phospholipid neo-determinant on apoptotic cells but not healthy cells, halts the progression of atherosclerosis in hypercholesterolemic mice (1), and can block in vivo and in vivo inflammatory responses to diverse agonists to TLR 3, 4, 7 and 9 (2) that is linked to the inhibition of central inflammatory signaling pathways.
To investigate for relationships between IgM antibodies to PC and other apoptosis-associated antigens with the clinical and laboratory features of SLE disease, we used standard ELISA to perform serologic surveys to PC, malondialdehyde (MDA) as well as cardiolipin (CL) and b2 glycoprotein I (b2 gp I) in 95 SLE patients from the well characterized Hopkins Lupus cohort.
In a pre-set series of analyses, for overall disease activity we found only modest inverse correlations with levels of IgM anti-MDA antibodies and the SLEDAI clinical disease activity index and Physicians global estimate (Pearson, P=0.01), but not with other IgM antibodies. Yet, patients without a history of past atherosclerotic cardiovascular (ASCVD) events (i.e., MI, CVA or TIA) had significantly higher IgM anti-PC levels (P= 0.00024, two-tailed t test) compared with those with past events, while there was no relationship with a history of documented lupus nephritis. In contrast, patients without lupus nephritis had higher levels of IgM anti-b2 gp I (P=0.003) and IgM anti-CL (P=0.0001) than in those with lupus nephritis, while there was no association between levels of IgM anti-b2 gp I with history of ASCVD events (P=0.46) and only a trend for IgM anti-CL (P=0.051). IgM anti-b2 gp I levels by themselves did not correlate with other thrombotic events (P=0.3). Patients with higher levels of IgM anti-MDA had modest associations with the absence of past ASCVD events (P=0.04) and the absence of lupus nephritis (P=0.04). Higher IgM anti-b2 gp I levels also correlated with lower C4 levels (Pearson, P=0.006), and a trend toward lower C3 levels (P=0.057). Otherwise there were no other significant associations with IgG anti-dsDNA or anti-C1q, or with C3 or C4, or ESR.
These findings support our hypothesis, based on murine studies and multiplex autoantibody microarray surveys of lupus twins (3), that some IgM autoantibodies are part of an evolutionarily conserved immune repertoire that provide homeostatic functions, which may protect from certain clinical features of autoimmune disease. Future studies will need to address whether these differences in antibody levels are present at earlier stages of disease development, which could provide valuable prognostic tools.
GJS is supported by grants from ALR, Arthritis Foundation, ACR REF Within Our Reach, NIAID R01 AI068063 and AI090118 and the Swedish Research Council (CG). MAP and the Hopkins Lupus Cohort are supported by NIAMS R01 AR43737 and the Johns Hopkins Univ GCRC M01-RR00052.
To cite this abstract, please use the following information:
Gronwall, Caroline, Akhter, Ehtisham, Petri, Michelle A., Silverman, Gregg J.; Protection from Cardiovascular Events and Nephritis in SLE Correlates with Levels of IgM Natural Autoantibodies to Different Apoptosis-Associated Antigens. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2121