Cytomegalovirus-specific neutralizing antibodies effectively prevent uncontrolled infection after allogeneic hematopoietic stem cell transplantation

Huiru Wang; Huilan Liu; Li Zhou; Dongyao Wang; Shushu Wang; Qian Liu; Yun Wu; Meijuan Tu; Zimin Sun; Xiaohu Zheng; Binqing Fu; Baolong Wang; Haiming Wei

doi:10.1016/j.isci.2022.105065

Cytomegalovirus-specific neutralizing antibodies effectively prevent uncontrolled infection after allogeneic hematopoietic stem cell transplantation

iScience. 2022 Sep 5;25(10):105065. doi: 10.1016/j.isci.2022.105065. eCollection 2022 Oct 21.

Authors

Huiru Wang^{1

2}, Huilan Liu^{1

3}, Li Zhou^{2

3}, Dongyao Wang^{2

3}, Shushu Wang^{2

4}, Qian Liu⁵, Yun Wu³, Meijuan Tu³, Zimin Sun³, Xiaohu Zheng², Binqing Fu², Baolong Wang⁶, Haiming Wei^{2

7}

Affiliations

¹ Department of Transfusion, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
² Institute of Immunology, University of Science and Technology of China, Hefei 230027, China.
³ Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
⁴ Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
⁵ Organ Transplant Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China.
⁶ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
⁷ Department of Geriatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

Abstract

Cytomegalovirus (CMV) infection remains one of the most frequent and life-threatening infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we comprehensively compared the immune cells of patients with uncontrolled and controlled CMV infection post-allo-HSCT and found that B-cells were extraordinarily insufficient because of impaired B-cells reconstitution in the uncontrolled infection group. Furthermore, in the controlled infection group, reconstructed B-cells showed signatures of mature B-cells, high expression of CXCR4 and IFITM1, and enrichment of CMV-associated B-cell receptors, which were lacking in the uncontrolled infection group. Consistently, sera from the uncontrolled infection group failed to inhibit CMV infection via neutralizing virus in vitro because of its lower content of anti-CMV-specific immunoglobulin G (IgG) than the controlled infection group. Overall, these results highlighted the contribution of B cells and anti-CMV-specific neutralizing IgGs to the restraint of CMV infection post-allo-HSCT, suggesting their potential as a supplementary treatment to improve outcomes.

Keywords: Immunology; Stem cells research; Virology.