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 replication, DNA or viral repl ...

s 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 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 diffe ...

Presentation

The 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 t ...

genetic condition in which a group of genes called major histocompatibility complex class II (MHC class II) are not expressed. The result is that the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

is severely compromised and cannot effectively fight

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

. 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 natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

precursor cells are improperly formed. Absolute T-cell count is also reduced, due to impaired development with the absence of MHC II. TAP (transporter associated with antigen presentation) deficiency syndrome is the best characterized of BLS I. Symptoms can include recurrent bacterial infections of the respiratory tract and chronic skin lesions. Bronchiectasis and respiratory failure and complete destruction of the nose and cerebral abscess are severe complications.

Diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

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 genes 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 normally regulate the expression (

gene transcription Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...

) of the MHC II genes. That is, one of the several proteins that are required to switch on MHC II genes in various cells types (primarily those in the immune system) 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 of the Xbox 5 (

RFX5 DNA-binding protein RFX5 is a protein that in humans is encoded by the ''RFX5'' gene. Function A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920 ...

) * RFX-associated protein (

RFXAP Regulatory factor X-associated protein is a protein that in humans is encoded by the ''RFXAP'' gene. Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune sys ...

) * RFX ankyrin repeats ( RFXANK; also known as RFXB)

BLS I

BLS I, also called "HLA class I deficiency", which is much more rare, is associated with

TAP2 TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2. Function The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport v ...

TAP1 Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the ''TAP1'' gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2. Function The membrane-associated protein en ...

, or TAPBP deficiencies. The TAP proteins are involved in pumping degraded cytosolic peptides across the endoplasmic reticulum membrane so they can bind 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. Just like BLS II, the defect isn't in the MHC protein, but rather another accessory protein.

Diagnosis

Classification

* Type 1: MHC class I * 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, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...

Treatment

Though BLSII is an attractive candidate for

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

, bone marrow transplant is currently the only treatment.

References

External links

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