Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 5 2025 09 16 593 606 Samin Sharafian Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mahya Mohammadi Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Samin Alavi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehrnaz Mesdaghi Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Reza Shiari Department of Pediatric Rheumatology, Mofid children hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Bibi Shahin Shamsian Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Peyman Eshghi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hedieh Haji Khodaverdi Khani Department of Immunology, Faculty of Medical Science, Shahed University, Tehran, Iran Hassan Abolghasemi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abdollah Karimi Pediatric Infections Research Center (PIRC), Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nasrin Behniafard Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Parastoo Mollaei Tavana Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohammad Mehdi Nasehi Department of Pediatric Neurology, Pediatric Neurology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mozhgan Hashemieh Department of Pediatrics Hematology/Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehran Khodashenas Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mahnaz Jamee Pediatric Nephrology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zahra Chavoshzadeh Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Narges Eslami Department of Allergy and Clinical Immunology, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2024 04 19 2025 02 10 It can sometimes be very difficult to control the manifestations of autoimmunity and lymphoproliferation in patients with primary immunodeficiency diseases, and there is no adequate response to first-line treatments. Rituximab (RTX), as a second-line treatment, is efficacious and well-tolerated for the management of these clinical manifestations. This retrospective study was conducted to analyze the clinical, immunological, and genetic findings together with the response rate to RTX therapy in subjects with inborn errors of immunity (IEI) and autoimmune or autoinflammatory manifestations. In this study, 23 individuals with IEI and autoimmune or lymphoproliferation manifestations who received RTX between April 2008 and 2021 were evaluated. Fifteen out of the 23 patients were female. The median age of cases was 12 years.  The moderate and severe adverse reactions, including fever, diarrhea, and anaphylaxis shock, were manifested during RTX infusion in 5 patients. In total, 86.9% of patients responded to rituximab (complete response: n=14, partial response: n=6) while three failed to respond. The median response time to RTX treatment was 50 days. All patients were given monthly intravenous immunoglobulin (IVIG) therapy. Pneumonia and candidiasis occurred in one patient a week after receiving the second injection of RTX. Eight patients expired during follow-up. In conclusion, the response rate of RTX could be improved through administering monthly IVIG for hypogammaglobulinemia treatment following RTX infusion. Early use of rituximab leads to a better response rate in comparison with late use of rituximab in multitreated refractory patients. The efficient cumulative dose of rituximab remains undefined.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4082 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4082/2197