title: ABO desensitization affects cellular immunity and infection control after renal transplantation.
abstract: The impact of ABO desensitization on overall immunity, infectious control, and alloreactivity remains unknown. We compared 35 ABO-incompatible kidney transplant recipients (KTRs) to a control of 62 ABO compatible KTRs. Samples were collected before, at +1, +2, +3, +6, and +12 months post-transplantation. CMV-, BKV-specific, and alloreactive T cells were measured using an interferon-γ ELISPOT assay. The extent of immunosuppression was quantified by enumeration of lymphocyte subpopulations and cytokines. No differences were observed for 5-year allograft survival and function between both groups (P > 0.05). However, ABO-incompatible KTRs were more likely to develop CMV infection, BKV-associated nephropathy, and severe sepsis (P = 0.001). Interestingly, ABO-incompatible KTRs with poor HLA-match showed the highest rates of infections and inferior allograft function (P < 0.05). CD3+, CD4+ T-cell counts, interferon-γ and IL-10 levels were lower in ABO-incompatible KTRs early post-transplantation (P < 0.05). Likewise, ABO-incompatible KTRs showed impaired BKV- and CMV-specific T-cell immunity (P < 0.05). ABO-incompatible KTRs showed lower frequencies of alloreactive T cells (P < 0.05). Our data suggest T-cell depletion due to ABO desensitization, which may contribute to the increased risk of T-cell-dependent infections. Elimination of B cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, plays a significant role in both impaired infection control and reduced alloreactive T-cell activation.
authors.affiliation: Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.|Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schachtner
authors.affiliation: Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Stein
authors.affiliation: Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.|Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D017951:Antigen Presentation; D001739:BK Virus; D000077552:Basiliximab; D001787:Blood Group Incompatibility / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000209:etiology; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D006082:Graft Enhancement, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017053:Infection Control; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008231:Lymphopenia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000453:epidemiology / Q000209:etiology; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000453:epidemiology / Q000209:etiology; D037182:T-Cell Antigen Receptor Specificity; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000209:etiology; D014766:Viremia / Q000453:epidemiology / Q000209:etiology; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; D000077552:Basiliximab
keywords: ABO incompatibility; T cells; alloreactivity; infection; lymphopenia; renal transplantation