Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain.
Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe, Valencia, Spain.
Front Immunol. 2024 Oct 16;15:1465159. doi: 10.3389/fimmu.2024.1465159. eCollection 2024.
Common Variable Immunodeficiency (CVID) represents a heterogenic group of primary immunodeficiencies (PID) characterized by impaired antibody production and susceptibility to infections. Non-infectious complications, such as autoimmune diseases, lymphoproliferative disorders, and malignancies, now significantly impact prognosis. Moreover, both hematologic and solid organ malignancies are more frequently observed in CVID patients compared to other PIDs. The risk factors for carcinogenesis in CVID remain largely unknown.
This multicenter study aims to characterize the clinical profile of cancer in CVID patients in Spain and to identify independent risk factors associated with malignancy development, focusing on the role of immune dysregulation.
A nationwide, cross-sectional study was conducted from November 2019 to May 2022, involving 17 hospitals treating PID patients in Spain. Data were collected systematically on demographics, infectious and non-infectious comorbidities, immunological parameters, and treatment. Statistical analysis, including multivariate logistic regression, was performed to identify risk factors associated to malignancy.
Of 250 CVID patients, 38 (15.26%) were diagnosed with cancer, predominantly non-Hodgkin lymphoma, gastric cancer, and lung adenocarcinoma. Cancer patients were significantly older (mean age 60.70 vs. 49.36 years, p<0.001) and had higher rates of immune dysregulation (81.58% vs. 59.7%, p=0.01). Immune dysregulation was an independent risk factor for cancer (OR 2.19, p=0.04), alongside previous immunosuppressant therapy (OR 2, p=0.031), higher IgM levels (OR 1.008 per SD, p=0.012), older age (OR 1.04, p<0.001), and lower CD4 cell counts at diagnosis (OR 0.997, p<0.001).
This study highlights the increased cancer risk in CVID patients, with immune dysregulation, prior immunosuppressant use, elevated IgM levels, and lower CD4 cell counts as conjointly associated. These findings underscore the need for vigilant cancer screening and tailored management strategies in CVID patients to improve outcomes. Future research should focus on elucidating the molecular mechanisms linking immune dysregulation and malignancy in CVID.
普通变异性免疫缺陷症（CVID）是一组以抗体产生受损和易感染为特征的原发性免疫缺陷症（PID）。非传染性并发症，如自身免疫性疾病、淋巴增生性疾病和恶性肿瘤，现在显著影响预后。此外，与其他 PID 相比，CVID 患者更常发生血液系统和实体器官恶性肿瘤。CVID 发生癌变的危险因素仍知之甚少。
本多中心研究旨在描述西班牙 CVID 患者癌症的临床特征，并确定与恶性肿瘤发展相关的独立危险因素，重点关注免疫失调的作用。
2019 年 11 月至 2022 年 5 月期间，我们进行了一项全国性的、横断面研究，涉及西班牙 17 家治疗 PID 患者的医院。系统收集了人口统计学、传染性和非传染性合并症、免疫参数和治疗情况的数据。进行了统计分析，包括多变量逻辑回归，以确定与恶性肿瘤相关的危险因素。
在 250 例 CVID 患者中，38 例（15.26%）被诊断患有癌症，主要为非霍奇金淋巴瘤、胃癌和肺腺癌。癌症患者的年龄明显较大（平均年龄 60.70 岁 vs. 49.36 岁，p<0.001），免疫失调发生率较高（81.58% vs. 59.7%，p=0.01）。免疫失调是癌症的独立危险因素（OR 2.19，p=0.04），同时还有先前的免疫抑制剂治疗（OR 2，p=0.031）、较高的 IgM 水平（OR 每 SD 增加 1.008，p=0.012）、年龄较大（OR 1.04，p<0.001）和诊断时 CD4 细胞计数较低（OR 0.997，p<0.001）。
本研究强调了 CVID 患者癌症风险增加，免疫失调、先前使用免疫抑制剂、IgM 水平升高和 CD4 细胞计数降低与癌症风险增加相关。这些发现强调了在 CVID 患者中需要进行警惕的癌症筛查和量身定制的管理策略，以改善预后。未来的研究应侧重于阐明 CVID 中免疫失调与恶性肿瘤之间的分子机制。
