Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Abstract

BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing

“…Combining Human Gene Mutation Database (HGMD) and PubMed, a total of 26 publications that reported SCID related to DCLRE1C until March 2021 were included for analysis. The genetic characteristics of patients from published studies ( Moshous et al, 2001 , 2003 ; Li et al, 2002 ; Kobayashi et al, 2003 ; Noordzij et al, 2003 ; Musio et al, 2005 ; Evans et al, 2006 ; Darroudi et al, 2007 ; van der Burg et al, 2007 ; Lagresle-Peyrou et al, 2008 ; Alsmadi et al, 2009 ; Pannicke et al, 2010 ; Woodbine et al, 2010 ; Ijspeert et al, 2011 ; Lee et al, 2011 , 2013 ; Tomashov-Matar et al, 2012 ; Bajin et al, 2013 ; Halbrich et al, 2013 ; Schuetz et al, 2014 ; Felgentreff et al, 2015 ; Lobachevsky et al, 2015 ; Volk et al, 2015 ; Al-Mousa et al, 2016 ; Dvorak et al, 2017 ; Luk et al, 2017 ; Rechavi et al, 2017 ; Stray-Pedersen et al, 2017 ; Tahiat et al, 2017 ; Al-Herz et al, 2018 ; Sundin et al, 2018 , 2019 ; Krantz et al, 2019 ; Wu et al, 2019 ; Dasouki et al, 2020 ; Fayez et al, 2020 ; Firtina et al, 2020 ; Kalina et al, 2020 ; Simon et al, 2020 ; Strand et al, 2020 ; Vignesh et al, 2020 ) are listed in Supplementary Table S3 . In total, 87 variants were recorded in HGMD as SCID.…”

Identification of key biomarkers and immune infiltration in renal interstitial fibrosis

“…Tryptophan aspartate-containing coat protein (TACO, also known as CORO1A or coronin-1), which is almost exclusively expressed in hematopoietic lineages, has been studied in the immunological field over the last few years and has been found to play an important role in T lymphocyte activation, CD4 + effector/memory T cell differentiation, and innate immunity (9)(10)(11). Many reports have demonstrated the contribution of CORO1A to inflammation and immune-related diseases, including multiple microorganism infection (12)(13)(14), spontaneous osteoarthritis (15), severe combined immune deficiency (16), and cancer (17). Recently, CORO1A was identified as a hub gene in chronic classic cardiomyopathy (CCC), characterized by severe cardiac inflammation and myocardial fibrosis (18).…”

Epstein–Barr Virus in Inborn Immunodeficiency—More Than Infection

“…Through the non-canonical Hippo pathway, STK4 exerts a variety of other functions on immune cells, such as extravasation and vesicle trafficking of neutrophils [ 74 , 137 ], humoral immunity [ 77 ] and T cell migration, development, and function [ 76 , 138 , 139 ]. T cells from STK4-deficient patients show reduced proliferation upon stimulation [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. Nehme et al could link decreased T cell proliferation with elevated T cell apoptosis due to increased FAS expression on the T cell surface [ 78 ].…”