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

Vignesh, Pandiarajan; Rawat, Amit; Kumrah, Rajni; Singh, Ankita; Anjani, Gummadi; Sharma, Manisha; Kaur, Anit; Johnson, Nameirakpam; Jindal, Ankur Kumar; Gupta, Anju; Khadwal, Alka; Saikia, Biman; Minz, Ranjana Walker; Sharma, Kaushal; Desai, Mukesh; Taur, Prasad; Gowri, Vijaya; Pandrowala, Ambreen; Dalvi, Aparna; Jodhawat, Neha; Kambli, Priyanka; Madkaikar, Manisha; Bhattad, Sagar; Ramprakash, Stalin; Cp, Raghuram; Jayaram, Ananthvikas; Sivasankaran, Meena; Munirathnam, Deenadayalan; Balaji, Sarath; Rajendran, Aruna; Aggarwal, Amita; Singh, Komal; Na, Fouzia; George, Biju; Mehta, Ankit; Lashkari, Harsha Prasada; Uppuluri, Ramya; Raj, Revathi; Bartakke, Sandip; Gupta, Kirti; Sreedharanunni, Sreejesh; Ogura, Yuichiro; Kato, Tamaki; Imai, Kohsuke; Chan, Koon Wing; Leung, Daniel; Ohara, Osamu; Nonoyama, Shigeaki; Hershfield, Michael S.; Lau, Yu Lung; Singh, Surjit

doi:10.3389/fimmu.2020.619146

Cited by 32 publications

(23 citation statements)

References 62 publications

(62 reference statements)

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“…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.…”

Section: Resultsmentioning

confidence: 99%

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

Xiao

et al. 2021

Front. Genet.

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Next-generation sequencing (NGS) has been used to detect severe combined immunodeficiency (SCID) in patients, and some patients with DNA cross-link repair 1C (DCLRE1C) variants have been identified. Moreover, some compound variants, such as copy number variants (CNV) and single nucleotide variants (SNV), have been reported. The purpose of this study was to expand the genetic data related to patients with SCID carrying the compound DCLRE1C variant. Whole-exome sequencing (WES) was performed for genetic analysis, and variants were verified by performing Sanger sequencing or quantitative PCR. Moreover, we searched PubMed and summarized the data of the reported variants. Four SCID patients with DCLRE1C variants were identified in this study. WES revealed a homozygous deletion in the DCLRE1C gene from exons 1–5 in patient 1, exons 1–3 deletion and a novel rare variant (c.92T>C, p.L31P) in patient 2, exons 1–3 deletion and a novel rare variant (c.328C>G, p.L110V) in patient 3, and exons 1–4 deletion and a novel frameshift variant (c.449dup, p.His151Alafs*20) in patient 4. Based on literature review, exons 1–3 was recognized as a hotspot region for deletion variation. Moreover, we found that compound variations (CNV + SNV) accounted for approximately 7% variations in all variants. When patients are screened for T-cell receptor excision circles (TRECs), NGS can be used to expand genetic testing. Deletion of the DCLRE1C gene should not be ignored when a variant has been found in patients with SCID.

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Section: Resultsmentioning

confidence: 99%

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

Xiao

et al. 2021

Front. Genet.

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“…In our cohort mycobacteria (8, 29.6%) was the most common organism isolated in patients with CGD. BCG-related complications were seen in 17/236 patients with CGD [19] and 27/254 children with SCID [20] had disseminated BCG infection in the large multicentric cohorts reported from India. We had 18 patients with complications related to BCG vaccination in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Profile of 208 Patients With Inborn Errors of Immunity at a Tertiary Care Center in South India

Bhattad

Mohite

Ramprakash

et al. 2022

Preprint

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Primary immune deficiencies better known as Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoinflammation, and malignancies.. Inborn Errors of Immunity are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care centre in South India were included in the study. The clinical features, laboratory findings including microbiologic and genetic data, treatment & outcome details were analyzed. The diagnosis of IEI was confirmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male to female ratio was 1.8:1. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a significant proportion of patients with DOCK8 deficiency (7.2%), LAD (6.2%), and six patients (2.8%) with autoinflammatory diseases. Autoimmunity was noted in forty-six (22%) patients during the course of their illness. Molecular testing was performed in 152 patients by exome sequencing on NGS platform and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the profile of 208 patients with IEI and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.

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“…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).…”

Section: Discussionmentioning

confidence: 99%

Identification of key biomarkers and immune infiltration in renal interstitial fibrosis

Hu¹,

Liu²,

Zhu³

et al. 2022

Ann Transl Med

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Background: Renal interstitial fibrosis (RIF) is the common final pathway that mediates almost all progressive renal diseases. However, the underlying mechanisms of RIF have not been fully elucidated.Therefore, the current study aimed to explore the etiology of RIF and identify the key targets and immune infiltration patterns of RIF.Methods: Ribonucleic acid (RNA)-seq data of RIF and normal samples were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to screen relevant modules associated with RIF. Differentially expressed genes (DEGs) between the RIF and normal samples were identified using the limma package. Machine learning methods were used to identify hub gene signatures related to RIF. Further biochemical approaches including quantitative polymerase chain reaction (qPCR), immunoblotting and immunohistochemistry experiments were performed to verify the hub signatures in the RIF samples. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the proportions of 28 immune cells in RIF and normal samples.Results: WGCNA showed 121 RIF-related genes. A total of 523 DEGs were found between the RIF and normal samples. By overlapping these genes, we obtained 78 RIF-related genes, which were mainly enriched in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with immunity and inflammation. Integrative analysis of machine learning methods showed prominin 1 (PROM1), tryptophan aspartate-containing coat protein (CORO1A), interferon-stimulated exonuclease gene 20 (ISG20), and tissue inhibitor matrix metalloproteinase 1 (TIMP1) as hub gene signatures in RIF. Further, receiver operating curve (ROC) curves implied the diagnostic role of ISG20 and CORO1A in RIF. The expression levels of ISG20 and CORO1A were significantly higher in fibrotic tubular cells and renal tissues based on biochemical approaches. The immune microenvironment was found to be markedly altered in the RIF samples, as 21 differentially infiltrated immune cells (DIICs) were found between RIF and normal samples.Conclusions: This study is the first to find that ISG20 and CORO1A are key biomarkers and to examine the landscape of immune infiltration in RIF. Our findings provide novel insights into the mechanisms and treatment of patients with RIF.

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

Cited by 32 publications

References 62 publications

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

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

Profile of 208 Patients With Inborn Errors of Immunity at a Tertiary Care Center in South India

Identification of key biomarkers and immune infiltration in renal interstitial fibrosis

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