A Novel RFXANK Mutation in a Chinese Child With MHC II Deficiency: Case Report and Literature Review

Abstract Major histocompatibility complex (MHC) II deficiency is a rare primary immunodeficiency disorder that is characterized by the deficiency of MHC class II molecules. The disease is caused by transcription factor mutations including class II transactivator (CIITA), regulatory factor X-5 (RFX5), RFX-associated protein (RFXAP), and RFXAP-containing ankyrin repeat (RFXANK), respectively. Mutations in the RFXANK gene account for >70% of all known patients worldwide. Herein, we reported a 10-month-old boy with MHC II deficiency caused by a novel mutation in the RFXANK gene (c.337 + 1G>C). The boy was admitted to the hospital due to pneumonia and diarrhea at 4 months of age. Genetic analysis revealed a novel homozygous mutation in the RFXANK gene, which derived from the c.337 + 1G>C heterozygous mutations in the RFXANK gene of his parents. The boy died 3 months after diagnosis. More than 200 cases have been reported, and a review of the literature revealed different mutation rates of 4 transcription factors in different countries or regions. This is the first case report of MHC II deficiency from East Asia. We also describe all gene mutations that cause MHC II deficiency and the epidemiology of MHC II deficiency with gene mutations in this paper.

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A novel mutation in RFXANK gene and low B cell count in a patient with MHC class II deficiency: a case report

Immunologic Research ◽

10.1007/s12026-020-09141-9 ◽

2020 ◽

Vol 68 (4) ◽

pp. 225-231

Author(s):

Farhad Abolnezhadian ◽

Razieh Dehghani ◽

Sajad Dehnavi ◽

Ali Khodadadi ◽

Mojtaba Shohan

Keyword(s):

Case Report ◽

B Cell ◽

Cell Count ◽

Mhc Class Ii ◽

Novel Mutation ◽

Class Ii ◽

Rfxank Gene ◽

Mhc Class Ii Deficiency

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MHC Class II Deficiency with Normal CD4+ T Cell Counts: A Case Report

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v17i6.624 ◽

2019 ◽

Author(s):

Farhad Abolnezhadian ◽

Ali Saieedi-Boroujen ◽

Sara Iranparast

Keyword(s):

Case Report ◽

T Cell ◽

Mhc Class Ii ◽

Class Ii ◽

Cd4 T Cell ◽

Homozygous Mutation ◽

Primary Immunodeficiency Disorder ◽

Hematopoietic Stem ◽

Cell Counts ◽

Mhc Class Ii Deficiency

Major histocompatibility complex (MHC) class II deficiency is a rare primary immunodeficiency disorder (PID) with less than 200 cases worldwide. Here, we report an 8 month–old girl with MHC class II deficiency with a novel homozygous mutation in RFXANK gene (NM_001278728: exon 5: c.495G>A: p.Trp165*) and normal CD4+ T cell counts, diagnosed by whole exome sequencing (WES) and negative HLA–DR proteins on peripheral blood mononuclear cell (PBMC) in flow cytometry. She was referred with pneumonia, prolonged fever, resistance to antibiotics (ceftriaxone, clindamycin, and vancomycin), and low serum immunoglobulin (IG) levels, while natural killer (NK), B, and T cells were normal. She received intra-venous immune-globulin (IVIG) replacement, broad spectrum antibiotics, and anti-fungal treatments. The presented case report is interesting not only because of the rarity of the PID but also due to normal CD4+ T cell counts. According to our experience, we suggest that physicians consider MHC class II deficiency in families with consanguineous marriages, even with normal CD4+ T cell counts. At the first, the diagnosis of the disease could be successfully perform using WES, and finally, treatment with hematopoietic stem cell transplantation can save the patients’ lives.

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Synaptic Clusters of MHC Class II Molecules Induced on DCs by Adhesion Molecule–mediated Initial T-Cell Scanning

Molecular Biology of the Cell ◽

10.1091/mbc.e05-01-0005 ◽

2005 ◽

Vol 16 (7) ◽

pp. 3314-3322 ◽

Cited By ~ 54

Author(s):

Hortensia de la Fuente ◽

María Mittelbrunn ◽

Lorena Sánchez-Martín ◽

Miguel Vicente-Manzanares ◽

Amalia Lamana ◽

...

Keyword(s):

T Cells ◽

Mhc Class Ii ◽

Class Ii ◽

Regulatory Pathway ◽

Immune Synapse ◽

Mhc Ii ◽

Cytoskeleton Reorganization ◽

Adhesive Contacts ◽

Enhance Antigen Presentation ◽

Mhc Class Ii Molecules

Initial adhesive contacts between T lymphocytes and dendritic cells (DCs) facilitate recognition of peptide-MHC complexes by the TCR. In this report, we studied the dynamic behavior of adhesion and Ag receptors on DCs during initial contacts with T-cells. Adhesion molecules LFA-1- and ICAM-1,3-GFP as well as MHC class II-GFP molecules were very rapidly concentrated at the DC contact area. Binding of ICAM-3, and ICAM-1 to a lesser extent, to LFA-1 expressed by mature but not immature DC, induced MHC-II clustering into the immune synapse. Also, ICAM-3 binding to DC induced the activation of the Vav1-Rac1 axis, a regulatory pathway involved in actin cytoskeleton reorganization, which was essential for MHC-II clustering on DCs. Our results support a model in which ICAM-mediated MHC-II clustering on DC constitutes a priming mechanism to enhance antigen presentation to T-cells.

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Major Histocompatibility Complex Class II+ Invariant Chain Negative Breast Cancer Cells Present Unique Peptides that Activate Tumor-specific T Cells from Breast Cancer Patients

Molecular & Cellular Proteomics ◽

10.1074/mcp.m112.019232 ◽

2012 ◽

Vol 11 (11) ◽

pp. 1457-1467 ◽

Cited By ~ 12

Author(s):

Olesya Chornoguz ◽

Alexei Gapeev ◽

Michael C. O'Neill ◽

Suzanne Ostrand-Rosenberg

Keyword(s):

Breast Cancer ◽

T Cells ◽

Cancer Cells ◽

Cancer Patients ◽

Mhc Class Ii ◽

Breast Cancer Cells ◽

Class Ii ◽

Breast Cancer Patients ◽

Mhc Ii ◽

Peptide Loading

The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes. Because Ii prevents peptide loading in neutral subcellular compartments, we reasoned that Ii− cells may present peptides not presented by Ii+ cells. Based on the hypothesis that patients are tolerant to MHC II-restricted tumor peptides presented by Ii+ cells, but will not be tolerant to novel peptides presented by Ii− cells, we generated MHC II vaccines to activate cancer patients' T cells. The vaccines are Ii− tumor cells expressing syngeneic HLA-DR and the costimulatory molecule CD80. We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii− MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii− cells present novel peptides. Ii expression was induced in the HLA-DR7 transfectants by transfection of Ii, and inhibited in the CIITA transfectants by RNA interference. Peptides were analyzed and binding affinity predicted by artificial neural net analysis. HLA-DR7-restricted peptides from Ii− and Ii+ cells do not differ in size or in subcellular location of their source proteins; however, a subset of HLA-DR7-restricted peptides of Ii− cells are not presented by Ii+ cells, and are derived from source proteins not used by Ii+ cells. Peptides from Ii− cells with the highest predicted HLA-DR7 binding affinity were synthesized, and activated tumor-specific HLA-DR7+ human T cells from healthy donors and breast cancer patients, demonstrating that the MS-identified peptides are bonafide tumor antigens. These results demonstrate that Ii regulates the repertoire of tumor peptides presented by MHC class II+ breast cancer cells and identify novel immunogenic MHC II-restricted peptides that are potential therapeutic reagents for cancer patients.

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A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

Oman Medical Journal ◽

10.5001/omj.2015.27 ◽

2015 ◽

Vol 30 (2) ◽

pp. 129-134 ◽

Cited By ~ 4

Author(s):

Aisha Al-Sinani ◽

Waad-Allah Mula-Abed ◽

Manal Al-Kindi ◽

Ghariba Al-Kusaibi ◽

Hanan Al-Azkawi ◽

...

Keyword(s):

Case Report ◽

Novel Mutation ◽

Hydroxysteroid Dehydrogenase ◽

Review Of Literature ◽

First Case ◽

Type 3

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MPYS, a Novel Membrane Tetraspanner, Is Associated with Major Histocompatibility Complex Class II and Mediates Transduction of Apoptotic Signals

Molecular and Cellular Biology ◽

10.1128/mcb.00640-08 ◽

2008 ◽

Vol 28 (16) ◽

pp. 5014-5026 ◽

Cited By ~ 243

Author(s):

Lei Jin ◽

Paul M. Waterman ◽

Karen R. Jonscher ◽

Cindy M. Short ◽

Nichole A. Reisdorph ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Cell Activation ◽

Cytoplasmic Tail ◽

Class Ii ◽

Antigenic Peptides ◽

Major Histocompatibility ◽

Mhc Ii ◽

Histocompatibility Complex ◽

Death Signals

ABSTRACT Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (∼140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.

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The first case report of a Chinese Hermansky–Pudlak syndrome patient with a novel mutation on HPS1 gene

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2009.07.007 ◽

2009 ◽

Vol 56 (2) ◽

pp. 130-132 ◽

Cited By ~ 15

Author(s):

Aihua Wei ◽

Shi Lian ◽

Lejin Wang ◽

Wei Li

Keyword(s):

Case Report ◽

Novel Mutation ◽

Syndrome Patient ◽

First Case ◽

Hermansky Pudlak Syndrome

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Novel mutation in the periaxin gene causal to Charcot–Marie–Tooth disease type 4F

Journal of International Medical Research ◽

10.1177/0300060519862064 ◽

2019 ◽

Vol 48 (2) ◽

pp. 030006051986206

Author(s):

Yu-hui Chen ◽

Hua Zhang ◽

Ling-bing Meng ◽

Xiao-yan Tang ◽

Tao Gong ◽

...

Keyword(s):

Novel Mutation ◽

Chinese Patients ◽

Homozygous Mutation ◽

Hereditary Neuropathy ◽

Limb Weakness ◽

Pes Cavus ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Protein Levels ◽

First Case

Charcot–Marie–Tooth (CMT) disease is the most common hereditary neuropathy. Mutations in the periaxin gene ( PRX) can cause CMT type 4F, an autosomal recessive neuropathy, which is clinically characterized by slowly progressive distal muscle atrophy and weakness, with pes cavus deformity of the foot, and the absence of deep tendon reflexes. To date, dozens of reports of PRX mutations have been published worldwide, but none have been reported in Chinese patients. Here, we describe a 14-year-old Chinese boy with neuropathy characterized by slowly progressive limb weakness and atrophy, as well as sensory ataxia, whose cerebrospinal protein levels were 1627 mg/L. Genetic analysis identified a novel homozygous mutation, c.1174C>T (p.R392X), in exon 6 of PRX, which is the first case of its kind recorded in China.

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