RESUMEN
Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (Pc = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (Pc = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.
Asunto(s)
Biomarcadores de Tumor/genética , Predisposición Genética a la Enfermedad , Variación Genética/genética , Antígenos HLA-C/genética , Melanoma/genética , Receptores KIR2DL3/genética , Neoplasias Cutáneas/genética , Femenino , Genotipo , Humanos , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Neoplasias Cutáneas/secundarioRESUMEN
The objective of this retrospective study was to evaluate the role of MICA in heart graft acceptance. Pre- and post-transplant sera from 31 patients were evaluated for MICA antibodies by cytotoxicity on recombinant cell lines and soluble MICA (sMICA) concentrations by ELISA. The results demonstrated that the patients with post-transplant anti-MICA antibodies were at a high risk for the development of severe acute rejection (AR) (p<0.03; OR=8.5). However, the presence of post-transplant sMICA was found to be associated with functioning grafts without AR episodes (p<0.03, OR=7.9). In this preliminary survey, the negative association of sMICA with AR was found to be in the absence of MICA antibodies. Further research is needed to clarify the role of sMICA in allograft acceptance. Post-transplant evaluation of humoral immune response to MICA and the measure of sMICA in patient's sera may provide a good predictor of AR.