Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India
Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T...
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00188/full |
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| author | Jahnavi Aluri Maya Gupta Aparna Dalvi Snehal Mhatre Manasi Kulkarni Gouri Hule Mukesh Desai Nitin Shah Prasad Taur Ramprasad Vedam Manisha Madkaikar |
| author_facet | Jahnavi Aluri Maya Gupta Aparna Dalvi Snehal Mhatre Manasi Kulkarni Gouri Hule Mukesh Desai Nitin Shah Prasad Taur Ramprasad Vedam Manisha Madkaikar |
| author_sort | Jahnavi Aluri |
| collection | DOAJ |
| description | Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR) expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs) were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T14:26:31Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bff3eb1923b1425eacff5d93a5c017ed2022-12-21T17:43:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00188318190Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from IndiaJahnavi Aluri0Maya Gupta1Aparna Dalvi2Snehal Mhatre3Manasi Kulkarni4Gouri Hule5Mukesh Desai6Nitin Shah7Prasad Taur8Ramprasad Vedam9Manisha Madkaikar10Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaDivision of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaPediatric Hematology-Oncology, P. D. Hinduja National Hospital & Research Center, Mumbai, IndiaDivision of Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, IndiaMedgenome Labs Pvt. Ltd., Bangalore, IndiaDepartment of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, IndiaMajor histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR) expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs) were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00188/fullprimary immunodeficiency disorderflow cytometryT cell receptor excision circlesnext-generation sequencinghematopoietic stem cell transplantation |
| spellingShingle | Jahnavi Aluri Maya Gupta Aparna Dalvi Snehal Mhatre Manasi Kulkarni Gouri Hule Mukesh Desai Nitin Shah Prasad Taur Ramprasad Vedam Manisha Madkaikar Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India Frontiers in Immunology primary immunodeficiency disorder flow cytometry T cell receptor excision circles next-generation sequencing hematopoietic stem cell transplantation |
| title | Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India |
| title_full | Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India |
| title_fullStr | Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India |
| title_full_unstemmed | Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India |
| title_short | Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India |
| title_sort | clinical immunological and molecular findings in five patients with major histocompatibility complex class ii deficiency from india |
| topic | primary immunodeficiency disorder flow cytometry T cell receptor excision circles next-generation sequencing hematopoietic stem cell transplantation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00188/full |
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