Bare lymphocyte syndrome is a condition caused by

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in certain genes of the

major histocompatibility complex The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...

or involved with the processing and presentation of MHC molecules. It is a form of

severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...

Presentation

Bare lymphocyte syndrome, type II (BLS II) is a rare

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

genetic condition in which a group of genes called the

class II (MHC class II) are not expressed. In BLS II the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

is severely compromised and cannot effectively fight

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

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

(SCID), in which

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

precursor cells are improperly formed. Absolute T-cell count is also reduced, due to impaired development with the absence of MHC II. 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 Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...

, respiratory failure and tissue erosion of the nose and cerebral abscess are severe complications. 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.

Diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

can be among the associated conditions.

Genetics

BLS II

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 biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

that code for proteins (

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

) 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 in Switzerland and Jeremy Boss at Emory University in Atlanta, Georgia. Mutation in any one of four genes can lead to BLS II. The genes' names are: * class II trans-activator (

CIITA 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 c ...

) * regulatory factor X5 (

RFX5 DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is ...

) * RFX-associated protein ( RFXAP) * RFX ankyrin repeats ( RFXANK; also known as RFXB)

BLS I

The comparatively rarer BLS I, also called "HLA class I deficiency" is associated with TAP2, TAP1, or TAPBP deficiencies. 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.

Diagnosis

Classification

* Type 1:

MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on ...

* Type 2:

MHC class II 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 cell ...

Treatment

References

External links

{{Immune disorders Autosomal recessive disorders Combined T and B–cell immunodeficiencies Noninfectious immunodeficiency-related cutaneous conditions Syndromes