Beksac Meral, Akin Hasan Yalim, Cengiz Seval Guldane, Yurdakul Mesutoglu Pinar, Anliacik Rıdvan Goksel, Anliacik Ezgi, Gurman Gunhan, Karaagaoglu Ergun, Dalva Klara
Department of Hematology, Ankara University Faculty of Medicine, Ankara, Turkey.
Department of Hematology, Ankara University Faculty of Medicine, Ankara, Turkey.
Clin Lymphoma Myeloma Leuk. 2023 May;23(5):394-400.e1. doi: 10.1016/j.clml.2023.02.007. Epub 2023 Feb 21.
Natural killer (NK) cells are known to have cytotoxic effects mediated through killer immunoglobulin-like receptors (KIRs) and their cognate ligands. Role of KIRs in myeloma is yet unresolved.
KIR genotypes and ligands of 204 newly diagnosed MM patients are compared with 424 healthy subjects. Statistical analysis included t-test, chi-square and binary logistic regression.
KIR ligands were significantly more (C2C2: 27.5% vs 15.1%; OR 2.128; 95% CI, 1.417-3.196; P < .001) or less (C1C2: 40.2% vs 51.9%; OR 0.623; 95% CI, 0.444-0.874; P = .006) frequent among MM. Co-occurrence of genotype AA with C2C2 was also higher in frequency among MM (OR 2.509; 95% CI, 1.171-5.378; P = .015) likewise cAB1 with C1C2 was less frequent (OR 0.553; 95% CI, 0.333-0.919; P = .021). Genotypes AA with C1C1, cAB1 with C1C2 or C1C2 alone were associated with a delay (median age: 61 [48-73]; P = .044; 62 [31-81]; P = .030 or 59 [31-85]; P = .028), but AA with C2C2 with an earlier age of onset (48 [29-77]; P = .042). In multivariate analysis including R-ISS, light chain, KIR genotype/ligands; ligand C1C2 (P = .02) and genotype AA-C1C1 (P = .037) were independently associated with age of onset ≥60.
C1C2 and C2C2 alone or in combination with KIR genotype (cAB1 and AA, respectively), is observed in less or higher frequency among MM cases and associated with delayed/earlier age of onset, respectively. Genotype AA-C1C1 although in similar frequency between patients and healthy subjects, is also associated with delay. To our knowledge, this is the first study demonstrating an association between KIR and MM onset age, independent from R-ISS or light chain type.
已知自然杀伤（NK）细胞具有通过杀伤细胞免疫球蛋白样受体（KIRs）及其同源配体介导的细胞毒性作用。KIRs在骨髓瘤中的作用尚未明确。
将204例新诊断的骨髓瘤患者的KIR基因型和配体与424名健康受试者进行比较。统计分析包括t检验、卡方检验和二元逻辑回归。
KIR配体在骨髓瘤患者中显著增多（C2C2：27.5% 对15.1%；OR 2.128；95% CI，1.417 - 3.196；P <.001）或减少（C1C2：40.2% 对51.9%；OR 0.623；95% CI，0.444 - 0.874；P =.006）。基因型AA与C2C2的共现频率在骨髓瘤患者中也较高（OR 2.509；95% CI，1.171 - 5.378；P =.015），同样，cAB1与C1C2的共现频率较低（OR 0.553；95% CI，0.333 - 0.919；P =.021）。基因型AA与C1C1、cAB1与C1C2或单独的C1C2与发病延迟相关（中位年龄：61 [48 - 73]；P =.044；62 [31 - 81]；P =.030或59 [31 - 85]；P =.028），但AA与C2C2与发病年龄较早相关（48 [29 - 77]；P =.042）。在包括R-ISS、轻链、KIR基因型/配体的多变量分析中；配体C1C2（P =.02）和基因型AA - C1C1（P =.037）与发病年龄≥60岁独立相关。
单独的C1C2和C2C2或分别与KIR基因型（分别为cAB1和AA）组合，在骨髓瘤病例中观察到频率较低或较高，分别与发病延迟/较早相关。基因型AA - C1C1虽然在患者和健康受试者中的频率相似，但也与发病延迟相关。据我们所知，这是第一项证明KIR与骨髓瘤发病年龄之间存在关联的研究，独立于R-ISS或轻链类型。
