Predictive and diagnostic biomarkers for cytomegalovirus infection in patients with rheumatic musculoskeletal diseases treated by high-dose glucocorticoid therapy: multicentre, prospective cohort study.

Abstract

Objectives: The incidence of cytomegalovirus (CMV) infection or disease in patients with rheumatic musculoskeletal diseases is reported to be 2%. Over half received pulsed methylprednisolone, and some experienced a fatal outcome. In this study, we aimed to explore predictive and diagnostic biomarkers for CMV infection or disease in such patients and compare them with biomarkers reported for immune reconstitution inflammatory syndrome (IRIS) in people with HIV.

Methods: In this multicentre prospective cohort study, we collected blood and saliva samples from 38 patients with rheumatic musculoskeletal disease before initiating high-dose glucocorticoid therapy, at the start of glucocorticoid tapering, at the onset of CMV infection, and 4 weeks later. Peripheral blood cell counts, flow cytometry for CD4, CD8, and Tregs, ELISA for cytokine/chemokine panels, and measurements of herpesvirus-derived DNA in saliva were performed.

Results: Lower white blood cells, CD4+ cells, IL-6, and interferon-γ levels and higher interferon-inducible protein (IP)-10 and granulysin levels at baseline could be predictive biomarkers for CMV infection. Furthermore, lower platelet counts and higher IL-10, IP-10, granulysin, TNF-a, IL-1ra, and IL-15 levels at the onset of CMV infection were found as diagnostic biomarkers for CMV infection. EBV, human herpes virus (HHV)-6, and HHV-7 DNA levels in the saliva were significantly increased after high-dose glucocorticoids, regardless of CMV infection.

Conclusions: We identified predictive and diagnostic biomarkers for CMV infection after high-dose glucocorticoid therapy for rheumatic musculoskeletal diseases. While similarities with IRIS biomarkers in patients living with HIV were observed, complete agreement could not be confirmed.