| Bare lymphocyte syndrome | |
|---|---|
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| Bare lymphocyte syndrome is autosomal recessive in inheritance | |
| Specialty | Hematology  |
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency. [1]
Bare lymphocyte syndrome, type II (BLS II) is a rare recessive genetic condition in which a group of genes called the major histocompatibility complex class II (MHC class II) are not expressed. [2]
In BLS II the immune system is severely compromised and cannot effectively fight infection due to an inability for antigen presenting cells to activate CD4⁺ t-cells as no TCR recognition of MHC II/peptide complexes can occur. Clinically, this is similar to severe combined immunodeficiency (SCID), in which lymphocyte precursor cells are improperly formed. Absolute T-cell count is also reduced, due to impaired development with the absence of MHC II. [3]
BLS I is characterised by a lack of MHC I molecules. Symptoms can include recurrent bacterial infections of the respiratory tract and chronic skin lesions. Bronchiectasis, respiratory failure and tissue erosion of the nose and cerebral abscess are severe complications. [4] Lack of MHC I expression on cell membranes causes self-immunity in NK and γδ T lymphocytes which are otherwhise downregulated by presence of MHC I.
The genetic basis for BLSII is not due to defects in the MHC II genes themselves. The genetic basis is the result of mutations in genes that code for proteins (transcription factors) that regulate the expression (gene transcription) of the MHC II genes. That is, one of the several proteins that are required to switch on MHC II genes is absent. The genes responsible were cloned by the laboratories of Bernard Mach [6] in Switzerland and Jeremy Boss [7] at Emory University in Atlanta, Georgia.
Mutation in any one of four genes can lead to BLS II. The genes' names are:
The comparatively rarer BLS I, also called "HLA class I deficiency" is associated with TAP2, TAP1, or TAPBP deficiencies. [8] TAP (Transporter associated with antigen processing) proteins are involved in pumping degraded cytosolic peptides across the endoplasmic reticulum membrane so they can bind to HLA class I. Once the peptide:HLA class I complex forms, it is transported to the membrane of the cell. However, a defect in the TAP proteins prevents pumping of peptides into the endoplasmic reticulum so no peptide:HLA class I complexes form and therefore no HLA class I is expressed on the membrane.
Though BLSII is an attractive candidate for gene therapy, bone marrow transplant is currently the only treatment.[ citation needed ]
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.
HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). HLA were originally defined as cell surface antigens that mediate graft-versus-host disease. Identification of these antigens has led to greater success and longevity in organ transplant.
HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.
Bare lymphocyte syndrome type II is a rare recessive genetic condition in which a group of genes called major histocompatibility complex class II are not expressed. The result is that the immune system is severely compromised and cannot effectively fight infection.
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, macrophages, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans.
CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection. Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma.
Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.
Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.
HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.
HLA class II histocompatibility antigen, DRB3-1 beta chain is a protein that in humans is encoded by the HLA-DRB3 gene.
HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.
HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.
DNA-binding protein RFX5 is a protein that in humans is encoded by the RFX5 gene.
HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.
HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.
HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system.
DNA-binding protein RFXANK is a protein that in humans is encoded by the RFXANK gene.
Regulatory factor X-associated protein is a protein that in humans is encoded by the RFXAP gene.
HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.