Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the

major histocompatibility complex 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 calle ...

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

Presentation

The bare lymphocyte syndrome, type II (BLS II) is a rare recessive genetic condition in which a group of genes called

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. 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 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 ...

and respiratory failure and complete destruction of the nose and cerebral abscess are severe complications. Diarrhea 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, mi ...

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 ( CIITA) * regulatory factor of the Xbox 5 ( RFX5) * RFX-associated protein ( RFXAP) * RFX ankyrin repeats (

RFXANK DNA-binding protein RFXANK is a protein that in humans is encoded by the ''RFXANK'' gene. Function Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune s ...

; also known as RFXB)

BLS I

BLS I, also called "HLA class I deficiency", which is much more rare, is associated with TAP2, TAP1, or

TAPBP TAP-associated glycoprotein, also known as tapasin or TAPBP, is a protein that in humans is encoded by the ''TAPBP'' gene. Function The ''TAPBP'' gene encodes a transmembrane glycoprotein that mediates interaction between newly assembled majo ...

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 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 plat ...

* Type 2: MHC class II

Treatment

Though BLSII is an attractive candidate for gene therapy, 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