Antígenos MICA y trasplante / MICA antigens and transplantation

Los antígenos leucocitarios humanos (HLA, del inglés human leukocyte antigens), codificados por los genes del complejo principal de histocompatibilidad (MHC, del inglés m ajor histocompatibility complex), actúan como inductores de las respuestas inmunitarias en el trasplante; sin embargo, los productos de los genes relacionados a cadenas MHC clase I (MIC, del inglés MHC class I chain-related genes), constituyen también uno de los blancos del rechazo. La familia de los genes MIC consta de siete miembros, de los cuales solo MICA y MICB son funcionales. Los transcriptos son glicoproteínas de superficie celular de 62 kDA que presentan homología en su secuencia con las moléculas HLA clase I y cuya función está relacionada con la inmunidad innata. En los órganos trasplantados ocurre un incremento en la expresión de los antígenos MICA como una señal temprana de "peligro" debido al trauma quirúrgico y la isquemia. Esta sobrexpresión antigénica puede llevar al rechazo mediado por anticuerpos anti-MICA que activan el complemento y por un incremento de la citotoxicidad debido a la estimulación en los linfocitos citolíticos naturales (NK, del inglés natural killer) y los linfocitos CD8+ &+ αß y γδ, del receptor conocido como NKG2D (NK grupo 2 miembro D(AU)

Human leukocyte antigens (HLA), encoded by major histocompatibility complex (MHC) genes, act as inducers of immune responses in transplantation. However, the products of the genes related to MHC class I chains (MIC) are also one of the targets of rejection. The family of MIC genes consists of seven members, of which only MICA and MICB are functional. Transcripts are cell surface glycoproteins of 62 kDa that exhibit homology in sequence with HLA class I molecules and whose function is related to innate immunity. In transplanted organs an increase in the expression of MICA antigens occurs as an early sign of "danger" due to surgical trauma and ischemia. This antigenic overexpression can lead to rejection mediated by complement-activating anti-MICA antibodies and by increased cytotoxicity due to stimulation in natural killer (NK) lymphocytes and CD8 + + αß and γδ lymphocytes. Receptor known as NKG2D (NK group 2 member D)(AU)

Anti-HLA and anti-MICA antibodies are positively correlated with transplanted kidney dysfunction / 中华微生物学和免疫学杂志

Objective To study the correlation between transplanted kidney dysfunction and oc-currence of the panel reactive antibody ( PRA, also referred as anti-HLA antibody ) and anti-Major-Histo-compatibility-Complex class Ⅰrelated chain A (MICA) antibody.Methods The tests for detecting PRA and anti-MICA antibody were performed on 679 renal transplant patients from December , 2009 to June, 2010 who received transplantation before 2008 in Beijing Friendship Hospital .Enzyme-Linked Immunosor-bent Assay ( ELISA) was used to detect anti-HLA antibody using LAT-1240 ( OneLambda Inc .) .MICA Ab-Scan Kit was adopted to detect anti-MICA antibody .Continuous observation of graft function was conducted . Results 108 out of 679 patients showed anti-HLA antibody and/or anti-MICA antibody positive results . Among them, 81 patients were positive only for anti-HLA antibody, 18 patients were positive only for anti-MICA antibody and other 9 patients showed anti-HLA and anti-MICA antibodies double positive .Among all of the kidney transplant patients with a failed or decreased renal function , 71 patients were positive for anti-HLA antibody;16 patients were positive for anti-MICA antibody;and other 9 patients were positive for both anti-HLA and anti-MICA antibodies .The results demonstrated that anti-HLA and anti-MICA antibodies af-fected the renal functions in patient with renal transplantation (χ2 =353.92, P <0.001).Conclusion Anti-HLA and MICA antibodies showed significant positive correlations with chronic allograft failure in the patients with renal transplantation .

Evidencia del impacto de los anticuerpos anti-HLA y anti-MICA en la pérdida del injerto renal / Evidence on the role of HLA and MICA antibodies in renal graft loss

Antecedentes: Los anticuerpos anti-HLA y anti-MICA se han asociado cada vez con mayor frecuencia a menor supervivencia del injerto renal. El objetivo de este estudio es comunicar la frecuencia de pérdida del injerto dos años después de la detección de anticuerpos anti-HLA, anti-MICA, o ambos, en un grupo de receptores de trasplante renal (RTR). Métodos: Estudiamos a 196 RTR con injerto funcional. El suero de los pacientes fue analizado para la presencia de anticuerpos IgG anti-HLA clase I y clase II con Luminex utilizando LABScreen®Mixed y LABScreen® PRA. La presencia de anticuerpos anti-MICA en el mismo suero se analizó por Luminex. Resultados: De 196 RTR (edad promedio 36.7 años, 42% sexo femenino), 124 (63.3%) fueron negativos a todos los anticuerpos estudiados y 72 (36.7%) fueron positivos: 34 para anticuerpos anti-HLA solo, 29 para anticuerpos anti-MICA solo y nueve para anticuerpos anti-HLA+anti-MICA. A una mediana de seguimiento de 20.5 meses (1.2-25.2), ocho pacientes perdieron el injerto por daño crónico del mismo, confirmado por biopsia: 2/124 (1.6%) del grupo de anticuerpos negativos y 6/72 (8.3%) del grupo de anticuerpos positivos, con una supervivencia del injerto significativamente inferior para el grupo de anticuerpos positivos (p=0.046, log-rank test). Conclusiones: La presencia de anticuerpos circulantes estuvo asociados con riesgo incrementado para pérdida del injerto; la coexistencia de anticuerpos anti-HLA y anti-MICA produjo el riesgo más alto para pérdida del injerto en la población analizada.

BACKGROUND: HLA and MICA antibodies are increasingly associated with poorer graft survival. The aim of this study is to report the frequency of graft loss 2 years after the detection of HLA abs and MICA abs among a group of kidney transplant recipients. METHODS: We tested 196 patients with a functioning graft. Sera were screened for HLA and MICA IgG abs by Luminex, using the LABScreen Mixed, and LABScreen PRA. The sera were screened for MICA abs by Luminex. RESULTS: Of 196 kidney transplant recipients (mean age 36.7 years, 42% female), one hundred twenty four (63.3%) were negative to all tested abs, and 72 (36.7%) were positive for: HLA abs alone = 34, MICA abs alone = 29, and HLA+MICA abs = 9. At a median followup of 20.5 (1.2-25.2) months, 8 patients lost their grafts due to biopsy-confirmed chronic allograft injury: 2/124 (1.6%) ab-negative, and 6/72 (8.3%) ab-positive, with a significantly lower survival for the Ab-positive group (p = 0.046, log-rank test). CONCLUSIONS: The presence of circulating abs was associated with an increased risk of graft loss, and the coexistence of HLA and MICA abs increases the risk of graft loss.