Levels of anti-CMV antibodies are modulated by the frequency and intensity of virus reactivations in kidney transplant patients

PLoS One. 2018 Apr 11;13(4):e0194789. doi: 10.1371/journal.pone.0194789. eCollection 2018.

Abstract

Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and increased risk of mortality. To test whether they represent a marker of infection history, we analyzed the effect of viral reactivations on the production of specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58 kidney transplant patients before transplantation and during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to calculate the intensity of the infection, we plotted the follow-up time of the infection on the x-axis and the number of DNA-CMV copies on the y-axis and calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed with flow cytometry, the cells were labelled with different monoclonal antibodies in order to distinguish their differentiation state, from naive T-cells to senescent T-cells. Peak viremia was significantly higher in patients experiencing a primary infection (VI) compared to patients experiencing viral reactivation (VR). Our data indicate that the overall CMV viral load over the course of a primary infection is significantly higher than in a reactivation of a previously established infection. Whereas patients who experienced an episode of CMV reactivation during the course of our observation showed increased levels of CMV-specific antibodies, patients who did not experience CMV reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an overall drop in antibody levels, probably due to the continuing immunosuppression after the renal transplant. We found a positive correlation between the CMV viremia over the course of the infection or reactivation and the CMV-specific antibody titers in the examined patients. We also observed a positive correlation between anti-CMV titers and T-cell differentiation. In conclusion, our data show that anti-CMV antibody titers are related to the course of CMV infection in kidney transplant patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Area Under Curve
  • CD8-Positive T-Lymphocytes / immunology
  • Cytomegalovirus
  • Cytomegalovirus Infections / immunology*
  • DNA, Viral
  • Female
  • Follow-Up Studies
  • HLA Antigens / immunology
  • Humans
  • Immunophenotyping
  • Immunosuppression Therapy
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / surgery
  • Kidney Failure, Chronic / virology
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Viral Load
  • Viremia / drug therapy
  • Virus Activation*

Substances

  • Antibodies, Viral
  • DNA, Viral
  • HLA Antigens

Grants and funding

This work was supported by grants PI14/01566 and PI17/00714 from Plan Estatal de I+D+i 2013-2016, co-funded by “Instituto de Salud Carlos III” and by “Fondo Europeo de Desarrollo Regional (FEDER).