Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

Jahnavi Aluri, Mukesh Desai, Maya Gupta, Aparna Dalvi, Antony Terance, Sergio D. Rosenzweig, Jennifer L. Stoddard, Julie E. Niemela, Vasundhara Tamankar, Snehal Mhatre, Umair Bargir, Manasi Kulkarni, Nitin Shah, Amita Aggarwal, Harsha Prasada Lashkari, Vidya Krishna, Geeta Govindaraj, Manas Kalra, Manisha Madkaikar

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Abstract

Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39%) followed by T-B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).

Original languageEnglish
Number of pages1
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 01-01-2019

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Severe Combined Immunodeficiency
India
Hematopoietic Stem Cell Transplantation
Polynucleotide 5'-Hydroxyl-Kinase
Oral Candidiasis
Failure to Thrive
Lymphopenia
Genetic Heterogeneity
Lymphocyte Count
Humoral Immunity
T-Cell Antigen Receptor
Cellular Immunity
Protein Kinases
Diarrhea
Pneumonia
Survival
DNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Aluri, Jahnavi ; Desai, Mukesh ; Gupta, Maya ; Dalvi, Aparna ; Terance, Antony ; Rosenzweig, Sergio D. ; Stoddard, Jennifer L. ; Niemela, Julie E. ; Tamankar, Vasundhara ; Mhatre, Snehal ; Bargir, Umair ; Kulkarni, Manasi ; Shah, Nitin ; Aggarwal, Amita ; Lashkari, Harsha Prasada ; Krishna, Vidya ; Govindaraj, Geeta ; Kalra, Manas ; Madkaikar, Manisha. / Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. In: Frontiers in Immunology. 2019 ; Vol. 10.
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abstract = "Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89{\%}) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66{\%}), failure to thrive (60{\%}), chronic diarrhea (35{\%}), gastrointestinal infection (21{\%}), and oral candidiasis (21{\%}). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63{\%} of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39{\%}) followed by T-B+ SCID (28{\%}). MHC class II deficiency accounted for 10.5{\%} of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).",
author = "Jahnavi Aluri and Mukesh Desai and Maya Gupta and Aparna Dalvi and Antony Terance and Rosenzweig, {Sergio D.} and Stoddard, {Jennifer L.} and Niemela, {Julie E.} and Vasundhara Tamankar and Snehal Mhatre and Umair Bargir and Manasi Kulkarni and Nitin Shah and Amita Aggarwal and Lashkari, {Harsha Prasada} and Vidya Krishna and Geeta Govindaraj and Manas Kalra and Manisha Madkaikar",
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Aluri, J, Desai, M, Gupta, M, Dalvi, A, Terance, A, Rosenzweig, SD, Stoddard, JL, Niemela, JE, Tamankar, V, Mhatre, S, Bargir, U, Kulkarni, M, Shah, N, Aggarwal, A, Lashkari, HP, Krishna, V, Govindaraj, G, Kalra, M & Madkaikar, M 2019, 'Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India', Frontiers in Immunology, vol. 10. https://doi.org/10.3389/fimmu.2019.00023

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. / Aluri, Jahnavi; Desai, Mukesh; Gupta, Maya; Dalvi, Aparna; Terance, Antony; Rosenzweig, Sergio D.; Stoddard, Jennifer L.; Niemela, Julie E.; Tamankar, Vasundhara; Mhatre, Snehal; Bargir, Umair; Kulkarni, Manasi; Shah, Nitin; Aggarwal, Amita; Lashkari, Harsha Prasada; Krishna, Vidya; Govindaraj, Geeta; Kalra, Manas; Madkaikar, Manisha.

In: Frontiers in Immunology, Vol. 10, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

AU - Aluri, Jahnavi

AU - Desai, Mukesh

AU - Gupta, Maya

AU - Dalvi, Aparna

AU - Terance, Antony

AU - Rosenzweig, Sergio D.

AU - Stoddard, Jennifer L.

AU - Niemela, Julie E.

AU - Tamankar, Vasundhara

AU - Mhatre, Snehal

AU - Bargir, Umair

AU - Kulkarni, Manasi

AU - Shah, Nitin

AU - Aggarwal, Amita

AU - Lashkari, Harsha Prasada

AU - Krishna, Vidya

AU - Govindaraj, Geeta

AU - Kalra, Manas

AU - Madkaikar, Manisha

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N2 - Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39%) followed by T-B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).

AB - Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39%) followed by T-B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL).

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