Full Papers
Predictive and diagnostic biomarkers for cytomegalovirus infection in patients with rheumatic musculoskeletal diseases treated by high-dose glucocorticoid therapy: multicentre, prospective cohort study
H. Sueki1, K. Noguchi2, B. Natsumoto3, K. Fujio4, Y. Hayashi5, Y. Kaneko6, T. Gono7, K. Wakabayashi8, H. Ito9, T. Yoshimoto10, A. Kokaze11, T. Otsuki12, Y. Shimizu13, T. Ito14, K. Okamoto15, S. Okugawa16, K. Moriya17, K. Matsui18
- Department of Dermatology, Showa University School of Medicine, Tokyo, Japan. hirsueki@med.showa-u.ac.jp
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Hyogo, Japan.
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan.
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan.
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
- Department of Dermatology, Showa University School of Medicine, Tokyo; and Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, Tokyo, Japan.
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, Tokyo, Japan.
- Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine, Tokyo, Japan.
- Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
- Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
- Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
- Department of Infectious Diseases, Institute of Science Tokyo Hospital, Tokyo, Japan.
- Department of Infectious Disease, The University of Tokyo Hospital, Tokyo, Japan.
- Department of Infectious Disease, The University of Tokyo Hospital, Tokyo, Japan.
- Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Hyogo, Japan.
CER18167
2025 Vol.43, N°3
PI 0497, PF 0506
Full Papers
PMID: 39907614 [PubMed]
Received: 17/09/2024
Accepted : 20/11/2024
In Press: 27/01/2025
Published: 12/03/2025
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.
