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Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency

Pashangzadeh S1≠, Delavari S1,2≠, Shad TM1, Salami F1,2, Rasouli SE1,3, Yazdani R1, Mahdaviani SA4, Nabavi M5, Aleyasin S6, Ahanchian H7, Azad FJ7, Chavoshzadeh Z8, Nazari F1, Momen T9, Sherkat R10, Abolnezhadian F11, Esmaeilzadeh H6, Fallahpour M5, Arshi S5, Bemanian MH5, Shokri S5, Ebrahimi SS12, Abolmolouki M1, Farid AS1, Rezaei A1, Esmaeili M1,2, Kalantari A13, Sadeghi-Shabestari M14, Shirkani A15, Behniafard N16, Khalili A17, Eslamian MH18, Cheraghi T19, Shafie A20, Tavakol M3, Khoshkhui M7, Iranparast S21, Shamshiri M21, Shahri MA1, Khazaei R11, Asadi M1, Babaha F1, Aghamohammadi A1, Rezaei N1,2, Abolhassani H1,22

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran
2Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran
3Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
4Pediatric Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
5Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
6Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7Allergy Research Center, Mashhad University Of Medical Sciences, Mashhad, Iran
8Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
9Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
10Immunodeficiency Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
11Department of Pediatrics, Abuzar Children's Hospital, Ahvaz University of Medical Sciences, Ahvaz, Iran
12Department of Immunology and Allergy, Kerman University of Medical Sciences, Kerman, Iran
13Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
14Department of Immunology and Allergy, Tabriz University of Medical Sciences, Tabriz, Iran
15Allergy and Clinical Immunology Department, Bushehr University of Medical Sciences, School of Medicine, Bushehr, Iran
16Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
17Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
18Department of Pediatrics, Hamedan University of Medical Sciences, Hamedan, Iran
19Department of Pediatrics, 17 Shahrivar Children’s Hospital, Guilan University of Medical Sciences, Rasht, Iran
20Department of Immunology, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
21Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
22Division of Clinical Immunology, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden
≠Salar pashangzadeh and Samaneh Delavari contributed equally to this work.

J Investig Allergol Clin Immunol 2024; Vol. 34(4)
doi: 10.18176/jiaci.0902

Background: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients.
Methods: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated.
Results: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups.
Conclusion: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients’ quality of life. 

Key words: Primary immunodeficiency, Inborn errors of immunity, Common variable immunodeficiency, Autoimmunity, Malignancy, Immune dysregulation