Autoimmunity Complications in Common Variable Immunodeficiency Patients; an update from the Iranian registry

Document Type : Original Article


Department of Immunology, faculty of medical sciences, Tarbiat Modares University



Introduction: Common Variable Immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency (PID) characterized by heterozygous manifestations, including infectious and non-infectious complications. The hallmark of disease is the development of recurrent sinopulmonary infections; however, different types of autoimmunity are frequently reported in CVID subjects. In this study, we aimed to provide an update report on various autoimmunity manifestations in a group of CVID patients in Iran.
Methods: Demographic, clinical and immunologic data of Iranian CVID cases who were followed up at children’s medical center were collected. Based on the presence of autoimmunity, patients were divided into two groups of autoimmunity and non-autoimmunity for further analyses.
Results: Among 301 CVID cases enrolled, 81 (26.9%) had autoimmunity which was mostly manifested as autoimmune cytopenia; 21 (24%) out of 81 individuals had immune thrombocytopenic purpura (ITP) and 14 (17.3%) patients showed autoimmune hemolytic anemia (AIHA). Rheumatologic autoimmune disorders like Juvenile Idiopathic Arthritis (JIA) and Juvenile Rheumatoid Arthritis (JRA) were observed in 7 (8.6%) and 5 (6.2%) individuals, respectively. Also, Inflammatory bowel disease 6 (7.4%) and vitiligo 7 (8.6%) were the most observed gastrointestinal and dermatologic autoimmune disorders in this study. Some of these conditions were concomitant in a single individual. Additionally, significant correlations were observed between autoimmunity and other complications including sinusitis (P=0.04), Bronchiectasis (P=0.002), Chronic diarrhea (P=0.000) and thrombocytopenia (P=0.000).
Conclusion: Autoimmunity and its association with other clinical manifestations should be paid more attention in CVID patients.


1. Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, et al. Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management. J Investig Allergol Clin Immunol. 2020;30(1):14-34. 2. Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, et al. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol. 2017;13(2):101-15. 3. Gereige JD, Maglione PJ. Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity. Front Immunol. 2019;10(2753):2753. 4.Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Ann Allergy Asthma Immunol. 2019;123(5):454-60. 5.Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008;28 Suppl 1:S42-5. 6.Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34-48. 7.Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277-86. 8.Mohammadinejad P, Aghamohammadi A, Abolhassani H, Sadaghiani MS, Abdollahzade S, Sadeghi B, et al. Pediatric patients with common variable immunodeficiency: longterm follow-up. J Investig Allergol Clin Immunol. 2012;22(3):208-14. 9.Odnoletkova I, Kindle G, Quinti I, Grimbacher B, Knerr V, Gathmann B, et al. The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data. Orphanet J Rare Dis. 2018;13(1):201. 10. Agarwal S, Mayer L. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol. 2013;11(9):1050-63. 11. Daniels JA, Lederman HM, Maitra A, Montgomery EA. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol. 2007;31(12):1800- 12. 12. Agarwal S, Smereka P, Harpaz N, Cunningham-Rundles C, Mayer L. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflamm Bowel Dis. 2011;17(1):251-9. 13. Gutierrez MJ, Sullivan KE, Fuleihan R, Bingham CO, 3rd. Phenotypic characterization of patients with rheumatologic manifestations of common variable immunodeficiency. Semin Arthritis Rheum. 2018;48(2):318-26. 14. Abolhassani H, Amirkashani D, Parvaneh N, Mohammadinejad P, Gharib B, Shahinpour S, et al. Autoimmune phenotype in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2013;23(5):323-9. 15. Ramirez-Vargas N, Arablin-Oropeza SE, Mojica-Martinez D, Yamazaki-Nakashimada MA, de la Luz Garcia-Cruz M, Teran-Juarez LM, et al. Clinical and immunological features of common variable immunodeficiency in Mexican patients. Allergol Immunopathol (Madr). 2014;42(3):235-40. 16. Megna M, Pecoraro A, Balato N, Villani A, Crescenzi L, Balato A, et al. Psoriasis in a cohort of patients with common variable immunodeficiency. Br J Dermatol. 2019;180(4):935- 6. 17. Xiao X, Miao Q, Chang C, Gershwin ME, Ma X. Common variable immunodeficiency and autoimmunity--an inconvenient truth. Autoimmun Rev. 2014;13(8):858-64. 18. Brandt D, Gershwin ME. Common variable immune deficiency and autoimmunity. Autoimmun Rev. 2006;5(7):465-70. 19. Valizadeh A, Yazdani R, Azizi G, Abolhassani H, Aghamohammadi A. A Comparison of Clinical and Immunologic Phenotypes in Familial and Sporadic Forms of Common Variable Immunodeficiency. Scand J Immunol. 2017;86(4):239-47. 20. Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117(4 Suppl):S525-53. 21. Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354-60.e4. 22. Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. 1993;86(1):31-42. 23. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650-7. 24. Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016;4(1):38-59. 25. Blanco E, Perez-Andres M, Arriba-Mendez S, Serrano C, Criado I, Del Pino-Molina L, et al. Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies. J Allergy Clin Immunol. 2019;144(3):809-24. 26. Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25(1):57-62. 27. Cunningham-Rundles C. Common variable immunodeficiency. Curr Allergy Asthma Rep. 2001;1(5):421-9. 28. Jorgensen SF, Troseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, et al. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol. 2016;9(6):1455-65. 29. Perreau M, Vigano S, Bellanger F, Pellaton C, Buss G, Comte D, et al. Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders. J Exp Med. 2014;211(10):2033-45. 30. Berbers RM, Nierkens S, van Laar JM, Bogaert D, Leavis HL. Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences. Trends Immunol. 2017;38(3):206-16. 31. Feuille EJ, Anooshiravani N, Sullivan KE, Fuleihan RL, Cunningham-Rundles C. Autoimmune Cytopenias and Associated Conditions in CVID: a Report From the USIDNET Registry. J Clin Immunol. 2018;38(1):28-34.