Harmful Effect of Preformed Anti-MICA Antibodies on Renal Allograft Evolution in Early Posttransplantation Period

• Published in: Transplantation Vol. 96; no. 1; pp. 70 - 78
• Main Authors: Sánchez-Zapardiel, Elena, Castro-Panete, María J, Castillo-Rama, Marcela, Morales, Pablo, Lora-Pablos, David, Valero-Hervás, Diana, Ruiz-García, Raquel, Apaza, Jacqueline, Talayero, Paloma, Andrés, Amado, Morales, José M, Paz-Artal, Estela
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health | Lippincott Williams & Wilkins 15-07-2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Child; Female; Graft Rejection - epidemiology; Graft Rejection - immunology; Graft Survival - immunology; Histocompatibility Antigens Class I - immunology; HLA Antigens - immunology; Humans; Isoantibodies - blood; Isoantibodies - immunology; Kidney Transplantation - immunology; Male; Middle Aged; Multivariate Analysis; Pregnancy; Retrospective Studies; Risk Factors; Transplantation, Homologous; Waiting Lists; Young Adult
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0b013e3182943506

BACKGROUNDPretransplantation anti–major histocompatibility complex class I chain–related molecule A (MICA) sensitization is an uncommon event and its role on kidney graft evolution is not completely defined.
METHODSA retrospective study of patients transplanted between 2005 and 2011 in our center (n=727) was performed. Recipients were classified in four groups, according either to multiplexed flow cytometry–recorded anti-human leukocyte antigen (HLA) and anti-MICA antibodies or to percent panel-reactive antibody (PRA; by complement-dependent cytotoxicity) and anti-MICA antibodies.
RESULTSIn the total cohort, 52 (7.15%) patients had preformed anti-MICA antibodies, and these were not related with anti-HLA, previous transplantations, or recipient female sex (potential pregnancies). Kaplan–Meier curves showed global allograft survival differences (P=0.042) mostly due to pronounced decrease in PRA+MICA+ group early after transplantation. Biopsy-proven allograft rejection rate increased after month 12 in PRA+MICA- group and was higher early after transplantation in PRA+MICA+ group (P=0.033). In paired comparisons, rejection incidence was superior in PRA+MICA- versus PRA-MICA- patients (17% vs. 7%; P=0.007) at 24 months, confirming the widely reported deleterious effect of PRA+ status, but at 3 months rejection was higher in PRA+MICA+ versus PRA-MICA- patients (14% vs. 2%; P=0.009). Among patients categorized according anti-HLA and anti-MICA antibodies, the most striking difference in rejection was observed at 3 months (8% in HLA-MICA+ vs. 2% in HLA-MICA- patients; P=0.032). In the multivariate analysis, HLA-MICA+ status at 3 months independently conferred the highest risk for rejection (odds ratio, 5.07; P=0.049).
CONCLUSIONSPretransplantation sensitization against MICA and HLA are independent events. Preformed anti-MICA antibodies independently increase risk for kidney rejection and enhance the deleterious effect of PRA+ status early after transplantation.