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Human Cytomegalovirus and Epstein-Barr virus specific immunity in patients with ulcerative colitis

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Abstract

Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in immunocompromised subjects, including patients suffering from ulcerative colitis (UC). We, therefore, aimed to investigate virus-specific immunity in UC patients. A cohort of 24 UC patients (14 responders and 10 refractory to therapy) and 26 control subjects was prospectively enrolled to undergo virus-specific serology (by ELISA assay) and assessment of both CD4+ and CD8+ virus-specific T-cell response (by interferon-γ enzyme-linked immunospotanalysis). In parallel, mucosal viral load was determined by quantitative real-time PCR and the values were correlated with both clinical and endoscopic indexes of activity. For statistics, the t-test, Mann–Withney test, Fisher’s exact test and Spearman rank correlation test were applied; p < 0.05 was considered significant. EBV-specific CD4+ and CD8+ T-cell responses were significantly lower in UC patients compared to controls (p < 0.0001 and p = 0.0006, respectively), whereas no difference was found for HCMV-specific T-cell response. When dividing the UC group according to response to therapy, both responders and refractory UC patients showed a deficient EBV-specific CD4+ T-cell response with respect to controls (p < 0.04 and p = 0.0003, respectively). Moreover, both EBV and HCMV mucosal loads were significantly higher in refractory UC than in responders and controls (p = 0.007 and 0.003; and p = 0.02 and 0.001, respectively), and correlated with activity indexes. Steroid therapy seemed the main risk factor for triggering EBV colitis. Finally, no cases of IgM positivity were found in the study population. An impaired EBV-specific immunity was clearly evident in UC patients, mostly in those refractory to therapy. The ELISPOT assay may serve as new tool for quantifying and monitoring virus-specific T-cell immunity in UC.

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Abbreviations

ELISPOT:

Enzyme-linked immunospot

EBV:

Epstein-Barr virus

EBER:

EBV-encoded RNAs

HCMV:

Human Cytomegalovirus

FITC:

Fluorescein isothiocyanate

IQR:

Interquartile range

PCR:

Polymerase chain reaction

SCCAI:

Simple Clinical Colitis Activity Index

UC:

Ulcerative colitis

UCEIS:

Ulcerative Colitis Endoscopic Index of Severity

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Funding

This study was financed in part by the San Matteo Hospital Foundation (Progetto di Ricerca Corrente) entitled: “Studio dell’infezione da Citomegalovirus umano ed Epstein-Barr virus nelle malattie infiammatorie croniche intestinali” (Project no. 821; code: 08064415). The sponsor had no role in the study design, collection, analysis or interpretation of the data, writing of the manuscript, nor in the decision to submit the paper for publication.

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Correspondence to Rachele Ciccocioppo or Peter Kruzliak.

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Ciccocioppo, R., Mengoli, C., Betti, E. et al. Human Cytomegalovirus and Epstein-Barr virus specific immunity in patients with ulcerative colitis. Clin Exp Med 21, 379–388 (2021). https://doi.org/10.1007/s10238-021-00702-2

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  • DOI: https://doi.org/10.1007/s10238-021-00702-2

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