Cosentini E, Gargiulo L, Bruno P, Lastraioli S, Risitano A, Camerlingo R, Luongo V, Serra M, Sica M, Garzillo C, Giani U, Notaro R, Alfinito F, Ruggiero G, Terrazzano G
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Napoli, Italy.
Tissue Antigens. 2012 Oct;80(4):322-7. doi: 10.1111/j.1399-0039.2012.01932.x. Epub 2012 Jul 17.
Paroxysmal nocturnal haemoglobinuria (PNH) is a haematopoietic disorder characterized by expansion of phosphatidylinositol glycan-A-defective progenitor(s). Immune-dependent mechanisms, likely involving a deranged T cell-dependent autoimmune response, have been consistently associated with the selection/dominance of PNH precursors. Natural killer (NK) lymphocytes might participate in PNH pathogenesis, but their role is still controversial. NK activity is dependent on the balance between activating and inhibiting signals. Key component in such regulatory network is represented by killer immunoglobulin-like receptors (KIR). KIR are also involved in the regulation of adaptive cytotoxic T cell response and associated with autoimmunity. This study investigated on the frequency of KIR genes and their known human leukocyte antigen (HLA) ligands in 53 PNH Italian patients. We observed increased frequency of genotypes characterized by ≤2 activating KIR as well as by the presence of an inhibitory/activating gene ratio ≥3.5. In addition, an increased matching between KIR-3DL1 and its ligand HLA-Bw4 was found. These genotypes might be associated with lower NK-dependent recognition of stress-related self molecules; this is conceivable with the hypothesis that an increased availability of specific T cell targets, not cleared by NK cells, could be involved in PNH pathogenesis. These data may provide new insights into autoimmune PNH pathogenesis.
阵发性夜间血红蛋白尿（PNH）是一种造血系统疾病，其特征是磷脂酰肌醇聚糖-A缺陷祖细胞的扩增。免疫依赖机制，可能涉及紊乱的T细胞依赖性自身免疫反应，一直与PNH前体的选择/优势相关。自然杀伤（NK）淋巴细胞可能参与PNH的发病机制，但其作用仍存在争议。NK活性取决于激活信号和抑制信号之间的平衡。这种调节网络的关键成分由杀伤细胞免疫球蛋白样受体（KIR）代表。KIR也参与适应性细胞毒性T细胞反应的调节并与自身免疫相关。本研究调查了53例意大利PNH患者中KIR基因及其已知人类白细胞抗原（HLA）配体的频率。我们观察到以≤2个激活KIR以及抑制/激活基因比率≥3.5为特征的基因型频率增加。此外，还发现KIR-3DL1与其配体HLA-Bw4之间的匹配增加。这些基因型可能与较低的NK依赖性应激相关自身分子识别有关；这与以下假设是可以想象的，即未被NK细胞清除的特定T细胞靶标的可用性增加可能参与PNH的发病机制。这些数据可能为自身免疫性PNH的发病机制提供新的见解。
