Background/Purpose:

Diastolic dysfunction and heart failure with preserved EF are more prevalent in RA. We have previously shown increased staining for citrullinated substrates in necropsied hearts of RA patients. We hypothesized that individuals with RA may generate antibodies against citrullinated myocardial proteins and that such antibodies may be associated with left ventricular (LV) dysfunction.

Methods:

59 sera from RA patients enrolled in a cohort study were incubated with uncitrullinated or citrullinated (exposed to peptidyl-arginine-deiminase-2 [PAD-2]) myocardial proteins (actin, myosin, tropomyosin, and troponin). Fluorescent anti-human IgG Fc antibody was added, rinsed, and mean fluorescence intensities (MFI) were recorded. Demographics, RA characteristics, and measures of LV function were compared between highest and lowest MFI tertiles for each protein in both citrullinated and uncitrullinated forms. The associations of anti-myocardial antibodies with measures of cardiac function, assessed by 3D echocardiography, were modeled using generalized linear models, adjusting for relevant confounders (variables associated with both LV function and seroreactivity to anti-myocardial proteins).

Results:

Patient sera with the highest tertile of seroreactivity against citrullinated (but not uncitrullinated) myosin showed multiple differences (p < 0.05) in measures of diastolic function: E/A ratio (0.95 vs 1.05), mean S wave (8.80 vs 10.09) and E/E’ ratio (9.64 vs 7.86) all indicated better diastolic function for patients in the lowest tertile. Systolic function between the seroreactivity tertiles was not different. Levels of other myocardial protein antibodies were not associated with diastolic function with the exception of S wave for citrullinated tropomyosin (p = 0.021). Multivariable analyses showed that the diastolic parameters E/E’ ratio and S wave (mean) remained significantly associated after controlling for RA duration and Tender Joint Count, previously identified potential confounders (Fig. 1).

Conclusion:

These data suggest that RA patients may generate antibodies against citrullinated myosin and that this may contribute to myocardial dysfunction in RA. Analyses of additional patient sera and ultimately verifying this observation in human myocardial tissue are needed.

Fig. 1: E/E’ ratio and S wave (mean) by tertiles of reactivity to citrullinated myosin.

E/E’ ratio and S wave (mean) are echocardiographic parameters that are increased (E/E’ ratio) and decreased (S wave [mean]) in diastolic dysfunction.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/seroreactivity-against-recombinant-citrullinated-myosin-is-associated-with-measures-of-diastolic-dysfunction-in-patients-with-rheumatoid-arthritis/