Human Cytomegalovirus (HCMV)-Specific Antibody Response and Development of Antibody-Dependent Cellular Cytotoxicity Against HCMV After Lung Transplantation

J Infect Dis. 2020 Jul 6;222(3):417-427. doi: 10.1093/infdis/jiaa097.

Abstract

Background: Human cytomegalovirus (HCMV) may cause severe infections in lung transplant recipients (LTRs). The impact of the host antibody (AB)-dependent cytotoxicity (ADCC) on HCMV is still unclear. Therefore, we analyzed the AB-response against HCMV glycoprotein B (gB) and the pentameric complex (PC) and the ADCC response in HCMV-seropositive (R+) LTRs and in seronegative recipients of positive organs (D+/R-).

Methods: Plasma samples were collected from 35 R+ and 28 D+/R- LTRs for 1 (R+) or 2 (D+/R-) years posttransplantation and from 114 healthy control persons. The PC- and gB-specific ABs were assessed by enzyme-linked immunosorbent assay. The ADCC was analyzed by focal expansion assay and CD107 cytotoxicity assay.

Results: In R+ LTRs, significantly higher gB-specific AB levels developed within 1 year posttransplantation than in controls (immunoglobulin [Ig]G1, P < .001; IgG3, P < .001). In addition, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared with controls (P < .001). In 23 D+R- patients, HCMV-specific ABs developed. Antibody-dependent cytotoxicity became detectable 3 months posttransplantation in these, with higher ADCC observed in viremic patients. Depletion of gB- and PC-specific ABs revealed that, in particular, gB-specific Abs were associated with the ADCC response.

Conclusions: We show that a strong ADCC is elicited after transplantation and is especially based on gB-specific ABs.

Keywords: ADCC; gB; human cytomegalovirus; neutralization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / analysis
  • Antibodies, Viral / classification
  • Antibodies, Viral / immunology*
  • Antibody Formation
  • Antibody-Dependent Cell Cytotoxicity / immunology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Transplant Recipients
  • Viral Envelope Proteins / immunology
  • Viremia
  • Young Adult

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus