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

• Published in: PloS one 2018-04, Vol.13 (4), p.e0194789-e0194789
• Main Authors: Iglesias-Escudero, María, Moro-García, Marco Antonio, Marcos-Fernández, Raquel, García-Torre, Alejandra, Álvarez-Argüelles, Marta Elena, Suárez-Fernández, María Luisa, Martínez-Camblor, Pablo, Rodríguez, Minerva, Alonso-Arias, Rebeca
• Format: Article
• Language: English
• Subjects: Activation; Adult; Aged; Aging; Analysis; Antibodies, Viral - blood; Area Under Curve; Biology and Life Sciences; Causes of; CD8-Positive T-Lymphocytes - immunology; Cell differentiation; Chronic illnesses; Correlation; Cytomegalovirus; Cytomegalovirus infections; Cytomegalovirus Infections - immunology; Cytometry; Deoxyribonucleic acid; Differentiation (biology); Disease; DNA; DNA, Viral; Female; Flow cytometry; Follow-Up Studies; Health aspects; HLA Antigens - immunology; Humans; Immune system; Immunoglobulins; Immunology; Immunophenotyping; Immunosuppression; Infections; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - surgery; Kidney Failure, Chronic - virology; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney transplants; Kidneys; Lymphocytes; Lymphocytes T; Male; Mathematical analysis; Medicine and Health Sciences; Middle Aged; Monoclonal antibodies; Mortality; Mortality risk; Nephrology; Older people; Patients; Research and Analysis Methods; Risk factors; Transplantation; Transplants & implants; Tumor necrosis factor-TNF; Viral Load; Viremia; Viremia - drug therapy; Virus Activation; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194789

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.