The impact of immune dysregulation on the risk of malignancy in common variable immunodeficiency: insights from a multicenter study.

Autor:	Cabañero-Navalon MD; 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., Garcia-Bustos V; Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain.; Severe Infection Research Group, Health Research Institute La Fe, Valencia, Spain., Balastegui-Martin H; 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., Bracke C; Infectious Diseases Service, Germans Trias i Pujol Hospital, Badalona, Spain.; Fight Infections Foundation, Germans Trias i Pujol Hospital, Badalona, Spain., Mateu L; Infectious Diseases Service, Germans Trias i Pujol Hospital, Badalona, Spain.; Fight Infections Foundation, Germans Trias i Pujol Hospital, Badalona, Spain., Solanich X; Internal Medicine Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.; Translational Medicine Area, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.; Department of Clinical Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain., Carrillo-Linares JL; Department of Internal Medicine, Virgen de la Victoria University Hospital, Málaga, Spain., Robles-Marhuenda A; Department of Internal Medicine, La Paz University Hospital, Madrid, Spain., Puchades F; Department of Internal Medicine, University General Hospital of Valencia, Valencia, Spain., Pelaez Ballesta A; Department of Internal Medicine, Rafael Méndez University Hospital, Murcia, Spain., Lopez-Osle N; Department of Internal Medicine, Cruces University Hospital, Bizkaia, Bilbao, Spain., Torralba-Cabeza MÁ; Unit for Rare Diseases, Internal Medicine Service, Lozano Blesa University Hospital, Zaragoza, Spain., Bielsa Masdeu AM; Department of Internal Medicine, Miguel Servet University Hospital, Zaragoza, Spain., Gil Niño J; Immunodeficiencies clinic, Internal Medicine Department, 12 de Octubre Hospital, Madrid, Spain., Tornador Gaya N; Department of Internal Medicine, University General Hospital of Castellón, Castellón, Castellon, Spain., Castellanos GP; Department of Internal Medicine, University General Hospital of Castellón, Castellón, Castellon, Spain., Sánchez-Martínez R; Internal Medicine Department, Dr. Balmis General University Hospital, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain., Barragán-Casas JM; Department of Internal Medicine, Complejo Asistencial de Ávila, Ávila, Spain., González-García A; Systemic Autoimmune Diseases Unit, Internal Medicine Service, Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain., Patier de la Peña JL; Systemic Autoimmune Diseases Unit, Internal Medicine Service, Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain., López-Wolf D; Department of Internal Medicine, University Hospital Alcorcón Foundation, Madrid, Spain., Rufete AM; Department of Internal Medicine, General University Hospital of Elche, Alicante, Spain., Canovas Mora A; Department of Internal Medicine, General University Hospital of Elche, Alicante, Spain., Moral Moral P; 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.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Oct 16; Vol. 15, pp. 1465159. Date of Electronic Publication: 2024 Oct 16 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1465159
Abstrakt:	Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Cabañero-Navalon, Garcia-Bustos, Balastegui-Martin, Bracke, Mateu, Solanich, Carrillo-Linares, Robles-Marhuenda, Puchades, Pelaez Ballesta, Lopez-Osle, Torralba-Cabeza, Bielsa Masdeu, Gil Niño, Tornador Gaya, Castellanos, Sánchez-Martínez, Barragán-Casas, González-García, Patier de la Peña, López-Wolf, Rufete, Canovas Mora and Moral Moral.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu