Epstein–Barr Virus Viral Load and T-Cell Exhaustion Markers Association with Rheumatoid Arthritis Disease Activity
DOI:
https://doi.org/10.32007/jfacmedbaghdad3368Keywords:
C-reactive protein, Disease Activity Score 28, Epstein–Barr Virus, Immune checkpoint, Rheumatoid arthritis, Systemic inflammationAbstract
Background: Treatment of refractory and severe rheumatoid arthritis remains challenging. Reactivation of Epstein–Barr virus may be associated with greater disease severity through enhanced autoimmunity, T-cell exhaustion, and immune-checkpoint dysregulation.
Objective: To evaluate the associations of Epstein–Barr virus reactivation and T-cell immune-checkpoint expression with rheumatoid arthritis disease activity.
Methods: Eighty patients with rheumatoid arthritis were assessed in a cross-sectional study and classified as being in remission or having mild, moderate, or high disease activity using the Disease Activity Score in 28 joints based on C-reactive protein. Epstein–Barr virus deoxyribonucleic acid was quantified by real-time quantitative polymerase chain reaction, and early-antigen immunoglobulin G was measured by chemiluminescence immunoassay. Programmed cell death protein 1 and cytotoxic T-lymphocyte–associated protein 4 expression on helper and cytotoxic T-cell subsets was evaluated by flow cytometry. Group differences were assessed using one-way analysis of variance or the Kruskal–Wallis test, as appropriate, and associations were examined using Spearman rank correlation.
Results: Epstein–Barr virus viral load and early-antigen immunoglobulin G levels increased significantly with disease activity. The high-activity group had a mean viral load of 10,470.16±5,918.54 copies per milliliter, whereas no viral load was detected in the remission group. Expression of programmed cell death protein 1 and cytotoxic T-lymphocyte–associated protein 4 on helper and cytotoxic T cells was highest in the high-activity group. Disease activity correlated positively with viral load (ρ=0.558), early-antigen immunoglobulin G (p=0.516), and the measured immune checkpoints (p=0.449–0.542).
Conclusion: Epstein–Barr virus reactivation and increased T-cell immune-checkpoint expression were associated with greater rheumatoid arthritis disease activity. Because the cross-sectional design cannot establish causality, longitudinal studies are needed to determine whether viral monitoring or interventions targeting viral replication and T-cell dysfunction may have clinical value.
Received: 11 May 2026
Revised: 25 Aug. 2026
Accepted: 07 Sept. 2026
Published Online: Sept. 2026
Published : 1st Oct.2026
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Copyright (c) 2026 Raed K. Naeem, Ahmed S. Abdulamir; Mohammed H. Alosami
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