Evaluating Autoimmunity in Patients with Agammaglobulinemia

Document Type : Original Article


1 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran

2 Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran


Background: Agammaglobulinemia is a primary immunodeficiency disorders (PID) which is identified by increased susceptibility to the bacterial infections, significant low antibodies and isohemagglutins and decreased peripheral B cells counts. Different clinical manifestations could be observed in these patients. Some of agammaglobulinemia patients manifest autoimmune disorders, while the association of autoimmunity and agammaglobulinemia is not clarified yet. In this study, we evaluated the frequency of autoimmunity in agammaglobulinemia patients and we compared their demographic, clinical and laboratory data in two groups of the patients with and without autoimmunity.
Material and Methods: The present study included 147 patients diagnosed with agammaglobulinemia who were diagnosed at the Research Centre for Immunodeficiencies at the children’s medical Centre. A comprehensive history, demographic information, clinical manifestations, laboratory data were obtained from all patients to assess the autoimmune complications.
Results: Among 147 agammaglobulinemia patients, we identified 21 (14.2%) (18 males and 3 females) agammaglobulinemia patients who had autoimmune disorders. In a total of the patients, the most prominent clinical presentation was respiratory infections (72.4%). Among autoimmune disorders, Juvenile Rheumatoid Arthritis was the most important autoimmunity (38%) following Immune thrombocytopenia with the frequency of 14%.
Conclusion: Autoimmune diseases are not very common among agammaglobulinemia patients, however, these disorders should be considered as an important factor for management in patients. Early diagnosis and proper management of autoimmunity in agammaglobulinemia cases lead to enhancement of patient's quality of life.


1. Shillitoe B, Gennery A. X-linked agammaglobulinaemia: outcomes in the modern era. Clinical Immunology. 2017;183:54-62. 2. Yazdani R, Abolhassani H, Kiaee F, Habibi S, Azizi G, Tavakol M, et al. Comparison of common monogenic defects in a large predominantly antibody deficiency cohort. The Journal of Allergy and Clinical Immunology: In Practice. 2019;7(3):864-78. e9. 3. Notarangelo LD. Primary immunodeficiencies. Journal of Allergy and Clinical Immunology. 2010;125(2):S182-S94. 4. Abolhassani H, Vitali M, Lougaris V, Giliani S, Parvaneh N, Parvaneh L, et al. Cohort of Iranian patients with congenital agammaglobulinemia: mutation analysis and novel gene defects. Expert review of clinical immunology. 2016;12(4):479-86. 5. Pessach IM. The relationship of x-linked primary immune deficiencies and autoimmunity. Current allergy and asthma reports. 2010;10(5):311-9. 6. Kwan-Morley J, Albert D. B-cell inhibitors as therapy for rheumatoid arthritis: an update. Current rheumatology reports. 2007;9(5):401-6. 7. Carvalho P, Costa C, Rodrigues M, Salvador M, da Silva JA P, Malcata A. Dermatomyositislike syndrome in x-linked agammaglobulinemia. Acta reumatologica portuguesa. 2016;41(1). 8. Howard V, Greene JM, Pahwa S, Winkelstein JA, Boyle JM, Kocak M, et al. The health status and quality of life of adults with X-linked agammaglobulinemia. Clinical immunology. 2006;118(2-3):201-8. 9. Sharma D, Guleria S, Suri D, Rawat A, Garg R, Singh S. A child with X-linked agammaglobulinemia and Kawasaki disease: an unusual association. Rheumatology international. 2017;37(8):1401-3. 10. Pessach IM, Notarangelo LD. X-linked primary immunodeficiencies as a bridge to better understandingX-chromosome related autoimmunity. Journal of autoimmunity. 2009;33(1):17-24. 11. Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmunity reviews. 2006;5(2):156-9. 12. Kubo T, Uchida Y, Watanabe Y, Abe M, Nakamura A, Ono M, et al. Augmented TLR9- induced Btk activation in PIR-B–deficient B-1 cells provokes excessive autoantibody production and autoimmunity. Journal of Experimental Medicine. 2009;206(9):1971-82. 13. Yong PF, Workman S, Wahid F, Exley A, Webster ADB, Ibrahim MA. Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency. Clinical Immunology. 2008;127(1):34-42. 14. Plebani A, Soresina A, Rondelli R, Amato GM, Azzari C, Cardinale F, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linkedagammaglobulinemia: an Italian multicenter study. Clinical immunology. 2002;104(3):221-30. 15. Aghamohammadi A, Allahverdi A, Abolhassani H, Moazzami K, Alizadeh H, Gharagozlou M, et al. Comparison of pulmonary diseases in common variable immunodeficiency and X‐linked agammaglobulinaemia. Respirology. 2010;15(2):289-95. 16. Sarmiento E, Mora R, Rodriguez-Mahou M, Rodriguez-Molina J, Fernandez-Cruz E, Carbone J. [Autoimmune disease in primary antibody deficiencies]. Allergologia et immunopathologia. 2005;33(2):69-73. 17. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, et al. Autoimmunity and inflammation in X-linked agammaglobulinemia. Journal of clinical immunology. 2014;34(6):627-32. 18. Ng YS, Wardemann H, Chelnis J, Cunningham-Rundles C, Meffre E. Bruton's tyrosine kinase is essential for human B cell tolerance. The Journal of experimental medicine. 2004;200(7):927-34. 19. Corneth OBJ, Klein Wolterink RGJ, Hendriks RW. BTK Signaling in B Cell Differentiation and Autoimmunity. Current topics in microbiology and immunology. 2016;393:67-105. 20. Azizi G, Ahmadi M, Abolhassani H, Yazdani R, Mohammadi H, Mirshafiey A, et al. Autoimmunity in Primary Antibody Deficiencies. International archives of allergy and immunology. 2016;171(3-4):180-93. 21. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, et al. Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol. 2014;34(6):627-32. 22. Bloom KA, Chung D, Cunningham-Rundles C. Osteoarticular infectious complications in patients with primary immunodeficiencies. Current opinion in rheumatology. 2008;20(4):480. 23. Verbruggen G, De Backer S, Deforce D, Demetter P, Cuvelier C, Veys E, et al. X linked agammaglobulinaemia and rheumatoid arthritis. Annals of the rheumatic diseases. 2005;64(7):1075-8. 24. Zhao Y, Marion TN. Multifaceted Roles of Neutrophils in Autoimmune Diseases. 2019;2019:7896738.