IntroductionHuman leukocyte antigen (HLA) polymorphisms have been associated with the development of various autoimmune diseases, as well as malignant neoplasms. Non-Hodgkin lymphomas (NHLs) are a heterogenous group of lymphoid malignancies in which a genetic substrate has been established and is deemed to play a crucial role in disease pathogenesis. This study aimed to identify whether variations in the HLA gene region were associated with diffuse large B-cell lymphoma (DLBCL) risk and prognosis.MethodsWe defined HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, HLA-DQB1) alleles in 60 patients with DLBCL and compared the results to those found by 236 healthy adult donors from the bone marrow bank of Northern Greece. HLA typing was performed by two molecular methods, Sequence - Specific Oligonucleotide HLA typing (SSO) and Sequence - Specific Primer HLA typing (SSP), from white blood cells recovered from peripheral blood. The phenotypic frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 between patients and controls were compared with the 2-sided Fisher’s exact test. Results with p-value <0.05 were considered statistically significant. Odds Ratios with 95% Confidence Intervals were calculated to further strengthen the results. The 2-sided Fisher’s exact test was also applied to alleles found only in one of the two groups, while the odds ratios together with the confidence intervals were corrected with Haldane-Anscombe method.ResultsAmong the studied HLA polymorphisms, the frequency HLA-C*12 allele was significantly lower in patients with DLBCL compared with control subjects (6.7% vs. 34.7%, OR = 0.16, 95% CI: 0.04–0.44). Frequency of HLA-B*39 was significantly lower in patients with DLBCL compared with controls, but due to the low frequency of this polymorphism in the studied population and small sample size, determinations regarding the significance of this findings were limited. Survival analysis revealed that the presence of HLA-C*12 was not associated with improved or worsened overall and progression-free survival. No statistically significant associations were observed in the phenotypic frequencies of HLA-A, HLA-DQB1, HLA-DRB1 and the rest of HLA-B alleles between the control and DLBCL groups.DiscussionCollectively, our results provide valuable insight regarding the role of HLA variations on DLBCL risk. Further studies are required to consolidate our findings and ascertain the clinical implications of these genetic variations on DLBCL management and prognosis.

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弥漫性大 B 细胞淋巴瘤患者的 HLA 变异及其与疾病风险和预后的关系：病例对照研究

简介人类白细胞抗原（HLA）多态性与各种自身免疫性疾病以及恶性肿瘤的发生有关。非霍奇金淋巴瘤 (NHL) 是一组异质性淋巴恶性肿瘤，其遗传基质已被确定，并被认为在疾病发病机制中发挥着至关重要的作用。本研究旨在确定 HLA 基因区域的变异是否与弥漫性大 B 细胞淋巴瘤 (DLBCL) 的风险和预后相关。方法我们定义了 HLA I 类（HLA-A、HLA-B、HLA-C）和 II 类（HLA-A、HLA-B、HLA-C）和研究人员对 60 名 DLBCL 患者的 HLA-DRB1、HLA-DQB1) 等位基因进行了研究，并将结果与​​来自希腊北部骨髓库的 236 名健康成年捐赠者的结果进行了比较。 HLA 分型通过两种分子方法进行，即序列 - 特异性寡核苷酸 HLA 分型 (SSO) 和序列 - 特异性引物 HLA 分型 (SSP)，从外周血中回收的白细胞进行。采用 2 边 Fisher 精确检验比较患者和对照之间的 HLA-A、HLA-B、HLA-C、HLA-DRB1 和 HLA-DQB1 表型频率。结果与p-值＜0.05被认为具有统计显着性。计算了 95% 置信区间的优势比，以进一步强化结果。 2 边 Fisher 精确检验也适用于仅在两组中发现的等位基因，同时使用 Haldane-Anscombe 方法校正优势比和置信区间。 结果在研究的 HLA 多态性中，HLA-C* 的频率与对照受试者相比，DLBCL 患者的 12 等位基因显着降低（6.7% vs. 34.7%，OR = 0.16，95% CI：0.04–0.44）。与对照组相比，DLBCL 患者的 HLA-B*39 频率显着较低，但由于研究人群中这种多态性的频率较低且样本量较小，因此关于这一发现的意义的确定是有限的。生存分析显示，HLA-C*12 的存在与总体生存率和无进展生存率的改善或恶化无关。在对照组和 DLBCL 组之间，HLA-A、HLA-DQB1、HLA-DRB1 和其余 HLA-B 等位基因的表型频率没有观察到统计学上显着的关联。 讨论总的来说，我们的结果提供了有关 HLA 变异作用的宝贵见解。关于 DLBCL 风险。需要进一步的研究来巩固我们的发现并确定这些遗传变异对 DLBCL 治疗和预后的临床影响。