Bare lymphocyte syndrome
Encyclopedia
Bare lymphocyte syndrome is a condition caused by mutation
s in certain genes of the major histocompatibility complex
. It is a form of severe combined immunodeficiency
.
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
is severely compromised and cannot effectively fight infection
. Clinically, this is similar to severe combined immunodeficiency
(SCID), in which lymphocyte
precursor cells are improperly formed.
Diarrhea
can be among the associated conditions.
that code for proteins (transcription factors) that normally 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 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:
, TAP1
, or TAPBP.
, bone marrow transplant is currently the only treatment.
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in certain genes of the major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
. It is a form of severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
.
Presentation
The bare lymphocyte syndrome, type II (BLS II) is a rare recessiveRecessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
genetic condition in which a group of genes called major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
class II (MHC class II) are not expressed.
The result is that the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
is severely compromised and cannot effectively fight infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. Clinically, this is similar to severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(SCID), in which lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
precursor cells are improperly formed.
Diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
can be among the associated conditions.
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 genesGênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
that code for proteins (transcription factors) that normally 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 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 (CIITACIITACIITA 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...
) - regulatory factor of the X box 5 (RFX5RFX5DNA-binding protein RFX5 is a protein that in humans is encoded by the RFX5 gene....
) - RFX-associated protein (RFXAPRFXAPRegulatory factor X-associated protein is a protein that in humans is encoded by the RFXAP gene.-Further reading:...
) - RFX ankyrin repeats (RFXANKRFXANKDNA-binding protein RFXANK is a protein that in humans is encoded by the RFXANK gene.-Interactions:RFXANK has been shown to interact with RFXAP and CIITA.-Further reading:...
; also known as RFXB)
BLS I
BLS I, also called "HLA class I deficiency", which is much more rare, is associated with TAP2TAP2
TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2....
, TAP1
TAP1
Antigen peptide transporter 1 is a protein that in humans is encoded by the TAP1 gene.-Interactions:TAP1 has been shown to interact with Tapasin and HLA-A.-Further reading:...
, or TAPBP.
Treatment
Though BLSII is an attractive candidate for gene therapyGene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
, bone marrow transplant is currently the only treatment.