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Immune response to cytomegalovirus affected RA patients’ reaction to DMARDs
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T-cell immunity associated with cytomegalovirus affected the response of patients with early rheumatoid arthritis to disease-modifying antirheumatic drug therapy, according to recent study results.
“Our findings suggest that in the future, it could be important to assess [cytomegalovirus] immune status when making decisions about medical treatments for rheumatoid arthritis,” researcher John M. Davis III, rheumatologist at Mayo Clinic, Rochester, Minn., told Healio.com.
John M. Davis III
Davis and colleagues conducted a 24-week prospective observational study of 71 consecutive patients with early rheumatoid arthritis (RA; mean age, 56 years; 66% women) who started treatment with disease-modifying antirheumatic drugs (DMARDs). Disease Activity Score 28 (DAS28) was used at baseline and after 21 to 24 weeks of follow-up.
The researchers analyzed multicytokine production from peripheral blood cells after incubation with stimuli that included human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates to determine immune response profiling. Principal components analysis (PCA) for each stimulus was used to identify profiles, which were correlated with DAS28 changes. Decreases of 1.2 or more were defined as clinically meaningful.
DAS28 changes correlated with the profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12 and interferon-gamma [IFN-g]) produced in response to CMV/EBV. Inadequate DAS28 response was predicted by “a higher magnitude” of CMV/EBV immune response profile (mean PCA-1 scores: 65.6 vs. 50.2; P=.029). IFN-g (P=.039) and IL-4 (P=.027) affected CMV/EBV response the most.
The CMV/EBV PCA-1 score increased from baseline to follow-up (mean, 11.6) for patients who achieved clinically meaningful DAS28 improvement, while patients with inadequate response to DMARD therapy experienced a decrease in CMV/EBV PCA-1 score (mean, –12.8; P=.002).
“Irrespective of DAS28 change, methotrexate use was associated with up-regulation of CMV/EBV response,” the researchers reported. “The CMV/EBV profile was associated with positive CMV IgG (P<.001), but not EBV IgG (P=.32), suggesting this response was related to CMV exposure.”
Disclosure: Mayo Foundation has submitted a patent application for the technique of multicytokine response profiling for assessing RA outcomes. Davis, Keith L. Knutson and Sherine E. Gabriel are listed as investors of technology in the patent application.
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