title: Low median fluorescence intensity could be a nonsafety concept of immunologic risk evaluation in patients with shared molecular eplets in kidney transplantation.
abstract: Human leukocyte antigen (HLA) antibodies are usually "epitope" and not "antigen" specific. This work presents an interesting case concerning Luminex median fluorescence intensity (MFI) levels in antibodies considered low risk (<1,000), but producing humoral rejection. These low-titer antibodies could play an important role in transplantation. A 42-year-old woman was retransplanted with a deceased donor with negative complement-dependent cytotoxicity cross-matching. Our patient was pretransplant (PrT) sensitized to HLA antigens (single antigens (SA) = 31%) for 1 previous transplant. Thus, the formerly detected sensitized antigens were A32, A30, A31, cross-reacting group 5C, and DQ3 with a MFI(max) ≈ 4,127. In the posttransplantation period (PTP), the patient exhibited important instability in renal function and we detected an increased SA percentage (61%) with MFI(max) = 15,029 (A*32) with other antigens (detected with a low PrT MFI [<1,000]) as anti-A*03 (MFI(max) = 13,301) and anti-A*11 (MFI(max) = 13,714) specificities. Anti-A*03 was a donor-specific antibody (DSA). Renal biopsy was compatible with humoral rejection. The patient was pulsed with methylprednisolone, plasmapheresis, and intravenous immunoglobulin without improvement. Thus, we added anti-CD20 and the initial clinical response was highly favorable. Biopsies resulted in suggestive rejection reversion. MFI A*03 DSA decreased to 6,908 and later to MFI(max) = 5,505. After a 6-month PTP, the patient is well with MFI(max) = 3,124. It was possible to define exactly the potential immunizing epitope eplets whose recognition determined the specific antibody production. A*32:01, A*30:01, A*31:01 (detected PrT), A*11:01, and A*03:01 (detected PTP) alleles have several shared eplets (62QE, 70AQS, and 76VGT), with 62QE being the only eplet present on all alleles. In conclusion, low MFI levels in antibodies considered low risk could be important in posttransplant humoral rejection, although the patient's renal function can be restored. Thus, specific shared eplets should always be investigated with respect to previous transplant mismatches.
authors.affiliation: Department of Immunology, University Hospital Virgen, Arrixaca, 30120 Murcia, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bosch
authors.forename: Santiago
authors.initials: S
authors.lastname: Llorente
authors.forename: Julio A
authors.initials: JA
authors.lastname: Diaz
authors.forename: Gema
authors.initials: G
authors.lastname: Salgado
authors.forename: Manuela
authors.initials: M
authors.lastname: López
authors.forename: Francisco
authors.initials: F
authors.lastname: Boix
authors.forename: Ruth
authors.initials: R
authors.lastname: López-Hernández
authors.forename: María J
authors.initials: MJ
authors.lastname: González-Soriano
authors.forename: José A
authors.initials: JA
authors.lastname: Campillo
authors.forename: María R
authors.initials: MR
authors.lastname: Moya-Quiles
authors.forename: Noelia
authors.initials: N
authors.lastname: Perez-Lopez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Minguela
authors.forename: Luisa
authors.initials: L
authors.lastname: Jimeno
authors.forename: María R
authors.initials: MR
authors.lastname: Alvarez-López
authors.forename: Manuel
authors.initials: M
authors.lastname: Muro
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D001706:Biopsy; D003429:Cross Reactions; D005260:Female; D005453:Fluorescence; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000097:blood* / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods / Q000592:standards; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage; D010956:Plasmapheresis; D018570:Risk Assessment; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D000069283:Rituximab; D008775:Methylprednisolone