Experiences from inborn errors of immunity registry of India: A preliminary report

Background and objectives Global estimates identify about 7,000 rare diseases affecting 6–8% of the population, with 80% being genetic. India lacks comprehensive data on their prevalence, distribution, and natural history. Inborn errors of immunity (IEI) registry was developed by Indian Council of Medical Research (ICMR) as part of a comprehensive multi-centric ‘National Registry for Rare and Other Inherited Disorders’, from centres which expressed interest in contributing to this national database in 2019. This study aims to establish an Indian rare-disease registry to assess disease burden, collect clinical and demographic data, understand natural history, support research on underlying mechanisms, create cohorts for evaluating therapies and orphan products, and strengthen connections among patients, families, and clinicians to improve comprehensive care across the country effectively. Methods After ethics approval from the participating centres, data were collected in a structured format developed jointly by ICMR- National Institute of Immunohaematology, Mumbai and Postgraduate Institute of Medical Education and Research, Chandigarh, identified as nodal centres for inborn errors of immunity (IEI) by ICMR. Cases with molecular confirmation of diagnosis or those satisfying the European Society for Immunodeficiencies (ESID) registry working definition in absence of molecular confirmation were included. The Data were compiled in excel format and analysed using Epi Info v7.2.5.0. Results Data for 676 patients enrolled between January 2019- October 2024 from six participating centres including ICMR-NIIH Mumbai, PGI Chandigarh, Apollo Chennai, JIPMER Pondicherry, Nizams Institute Hyderabad, and Sir Gangaram Hospital Delhi was analysed. Immunodeficiencies affecting cellular and humoral immunity (CID) and CID with associated or syndromic features (n=187,27.6%), predominantly antibody deficiency (n=146,21.6%), congenital defects of phagocyte number or function (n=117,17.3%) were the most frequent IEIs. The median age of presentation was 16 (IQR 4,63) months and diagnostic delay of 16 (IQR 3,55) months. The presenting clinical manifestations comprised of recurrent infections (n=459,67.9%), autoimmunity or auto-inflammation (n=292,43.2%), adverse effect following immunisation (n=38,5.6%), and malignancy (n=5,0.73%). 103/146 (70%) patients with antibody deficiency received IVIG and 90 (13.3%) IEI patients underwent hematopoietic stem cell transplant. On follow up, 118 (17.4%) patients died due to infections by 2024. Interpretation and conclusions The IEI registry developed by ICMR as an attempt to maintain a patient database gives us insights on the demographic, clinical presentation, diagnostic-delay and treatment outcomes of these disorders.