Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

Lauren Stern; Helen M McGuire; Selmir Avdic; Emily Blyth; David Gottlieb; Ellis Patrick; Allison Abendroth; Barry Slobedman

doi:10.1002/cti2.1473

Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

Clin Transl Immunology. 2023 Nov 28;12(12):e16815. doi: 10.1002/cti2.1473. eCollection 2023.

Authors

Lauren Stern^{1

2}, Helen M McGuire^{1

2}, Selmir Avdic³, Emily Blyth^{3

4

5}, David Gottlieb^{3

4

5}, Ellis Patrick^{3

6}, Allison Abendroth^{1

2}, Barry Slobedman^{1

2}

Affiliations

¹ Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health The University of Sydney Sydney NSW Australia.
² Charles Perkins Centre The University of Sydney Sydney NSW Australia.
³ Westmead Institute for Medical Research The University of Sydney Sydney NSW Australia.
⁴ Blood Transplant and Cell Therapies Program, Department of Haematology Westmead Hospital Sydney NSW Australia.
⁵ Faculty of Medicine and Health, Sydney Medical School The University of Sydney Sydney NSW Australia.
⁶ School of Mathematics and Statistics The University of Sydney Sydney NSW Australia.

Abstract

Objectives: Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo-HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time-points in the first 100-day post-transplant.

Methods: The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead-based immunoassay. Cytokine/chemokine concentrations were compared in patients with high-level HCMV DNAemia, low-level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.

Results: Increased plasma levels of T helper 1-type cytokines/chemokines (TNF, IL-18, IP-10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non-reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high-level HCMV DNAemia (810-52 740 copies/mL) vs. low-level HCMV DNAemia (< 250 copies/mL). High-level HCMV reactivators, but not low-level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP-1α, MIP-1β, TNF, LT-α, IL-13, IL-9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.

Conclusion: This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo-HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.

Keywords: allo‐HSCT; chemokines; cytokines; human cytomegalovirus; transplant; viral reactivation.