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{{Short description|A rare immunodeficiency disorder}}
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'''Bare lymphocyte syndrome''' is a condition caused by [[mutation]]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]].<ref name="pmid10938133">{{cite journal |vauthors=DeSandro AM, Nagarajan UM, Boss JM |title=Associations and interactions between bare lymphocyte syndrome factors |journal=Mol. Cell. Biol. |volume=20 |issue=17 |pages=6587–99 |date=September 2000 |pmid=10938133 |pmc=86141 |doi= 10.1128/MCB.20.17.6587-6599.2000}}</ref>


==Presentation==
'''Bare lymphocyte syndrome''' (BLS) is a rare [[immunodeficiency disorder]] characterized by the absence or significant reduction of [[major histocompatibility complex]] (MHC) molecules on the surface of [[lymphocytes]]. This condition leads to severe immune system dysfunction, as MHC molecules are crucial for the immune system's ability to recognize and respond to foreign antigens.
The bare lymphocyte syndrome, type II (BLS II) is a rare [[recessive]] 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. As a notable contrast, however, bare lymphocyte syndrome does not result in decreased B- and T-cell counts, as the development of these cells is not impaired.
==Classification==
Bare lymphocyte syndrome is classified into two main types based on the specific MHC molecules affected:


== Symptoms ==
* '''Type I BLS''': This type involves a deficiency in MHC class I molecules. It is often associated with chronic [[lung infections]] and [[granulomatous skin lesions]].
TAP deficiency syndrome is the best characterized of BLS I.<ref name=":0">{{Cite journal|last=Gadola|first=S. D.|last2=Moins-Teisserenc|first2=H. T.|last3=Trowsdale|first3=J.|last4=Gross|first4=W. L.|last5=Cerundolo|first5=V.|date=August 2000|title=TAP deficiency syndrome. IMMUNODEFICIENCY REVIEW|journal=Clinical and Experimental Immunology|language=en|volume=121|issue=2|pages=173–178|doi=10.1046/j.1365-2249.2000.01264.x|issn=0009-9104|pmc=1905688|pmid=10931128}}</ref> 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.<ref name=":0" />


[[Diarrhea]] can be among the associated conditions.<ref name="urlImmunologic Disease and Disorders">{{cite web|url=http://www.lib.mcg.edu/edu/esimmuno/casehist/diseases/barelymp.htm |title=Immunologic Disease and Disorders |url-status=dead |archiveurl=https://web.archive.org/web/20070217183003/http://www.lib.mcg.edu/edu/esimmuno/casehist/diseases/barelymp.htm |archivedate=2007-02-17 }}</ref>
* '''Type II BLS''': This type involves a deficiency in MHC class II molecules. It is more severe than Type I and is characterized by recurrent infections, failure to thrive, and often leads to early childhood mortality if untreated.


==Genetics==
==Pathophysiology==
The pathophysiology of bare lymphocyte syndrome involves genetic mutations that affect the expression of MHC molecules on the surface of [[antigen-presenting cells]]. In Type I BLS, mutations typically occur in genes responsible for the transport and processing of MHC class I molecules. In Type II BLS, mutations affect the [[transcription factors]] necessary for the expression of MHC class II molecules.


===BLS II===
==Clinical Features==
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 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<ref>{{cite journal |vauthors=Reith W, Mach B |title=The bare lymphocyte syndrome and the regulation of MHC expression |journal=Annu. Rev. Immunol. |volume=19 |issue= |pages=331–73 |year=2001 |pmid=11244040 |doi=10.1146/annurev.immunol.19.1.331}}</ref> in Switzerland and Jeremy Boss<ref>{{cite journal |vauthors=DeSandro A, Nagarajan UM, Boss JM |title=The bare lymphocyte syndrome: molecular clues to the transcriptional regulation of major histocompatibility complex class II genes |journal=Am. J. Hum. Genet. |volume=65 |issue=2 |pages=279–86 |year=1999 |pmid=10417269 |doi=10.1086/302519 |pmc=1377925}}</ref> at Emory University in Atlanta, Georgia.
Patients with bare lymphocyte syndrome present with a variety of clinical features depending on the type:


Mutation in any one of four genes can lead to BLS II.  The genes' names are:  
* '''Type I BLS''': Patients may experience recurrent [[respiratory tract infections]], [[bronchiectasis]], and skin lesions. Despite the absence of MHC class I molecules, these patients often have normal [[T-cell]] counts.
* class II trans-activator ([[CIITA]])
* regulatory factor of the Xbox 5 ([[RFX5]])
* RFX-associated protein ([[RFXAP]])
* RFX ankyrin repeats ([[RFXANK]]; also known as RFXB)


===BLS I===
* '''Type II BLS''': This type presents with severe combined immunodeficiency-like symptoms, including recurrent bacterial, viral, and fungal infections, [[chronic diarrhea]], and [[failure to thrive]].
BLS I, also called "HLA class I deficiency", which is much more rare, is associated with [[TAP2]], [[TAP1]], or [[TAPBP]] deficiencies.<ref name=OMIM>{{OMIM|604571|title=BARE LYMPHOCYTE SYNDROME, TYPE I}}</ref> 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==
==Diagnosis==
===Classification===
Diagnosis of bare lymphocyte syndrome involves a combination of clinical evaluation, laboratory tests, and genetic analysis. Key diagnostic tests include:
* Type 1: [[MHC class I]]
 
* Type 2: [[MHC class II]]
* [[Flow cytometry]] to assess the expression of MHC molecules on lymphocytes.
* Genetic testing to identify mutations in genes associated with MHC expression.
* Immunological assays to evaluate the function of T-cells and other immune components.


==Treatment==
==Treatment==
Though BLSII is an attractive candidate for [[gene therapy]], bone marrow transplant is currently the only treatment.
The treatment of bare lymphocyte syndrome is primarily supportive and may include:
 
* [[Antibiotic]] prophylaxis to prevent infections.
* [[Immunoglobulin replacement therapy]] to provide passive immunity.
* [[Hematopoietic stem cell transplantation]] (HSCT) is the only curative treatment, particularly for Type II BLS.


== References ==
==Prognosis==
{{Reflist}}
The prognosis for patients with bare lymphocyte syndrome varies depending on the type and severity of the condition. Type I BLS generally has a better prognosis with appropriate management, while Type II BLS often requires early intervention with HSCT to improve survival outcomes.


== External links ==
==Related pages==
{{Medical resources
* [[Immunodeficiency]]
|  DiseasesDB    = 29570
* [[Major histocompatibility complex]]
|    ICD10          = {{ICD10|D|81|6|d|80}}
* [[Hematopoietic stem cell transplantation]]
|  ICD9          =
|  ICDO          =
|  OMIM          = 604571
|  OMIM_mult      = {{OMIM|209920||none}}
|    MedlinePlus    =
|  eMedicineSubj  =
|  eMedicineTopic =
|  MeshID        = D016511
}}
{{Immune disorders}}


[[Category:Autosomal recessive disorders]]
[[Category:Immunodeficiency disorders]]
[[Category:Combined T and B–cell immunodeficiencies]]
[[Category:Genetic disorders]]
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]]
[[Category:Syndromes]]
<gallery>
File:Autosomal recessive - en.svg|Bare lymphocyte syndrome
</gallery>

Revision as of 19:05, 22 March 2025

A rare immunodeficiency disorder



Bare lymphocyte syndrome (BLS) is a rare immunodeficiency disorder characterized by the absence or significant reduction of major histocompatibility complex (MHC) molecules on the surface of lymphocytes. This condition leads to severe immune system dysfunction, as MHC molecules are crucial for the immune system's ability to recognize and respond to foreign antigens.

Classification

Bare lymphocyte syndrome is classified into two main types based on the specific MHC molecules affected:

  • Type II BLS: This type involves a deficiency in MHC class II molecules. It is more severe than Type I and is characterized by recurrent infections, failure to thrive, and often leads to early childhood mortality if untreated.

Pathophysiology

The pathophysiology of bare lymphocyte syndrome involves genetic mutations that affect the expression of MHC molecules on the surface of antigen-presenting cells. In Type I BLS, mutations typically occur in genes responsible for the transport and processing of MHC class I molecules. In Type II BLS, mutations affect the transcription factors necessary for the expression of MHC class II molecules.

Clinical Features

Patients with bare lymphocyte syndrome present with a variety of clinical features depending on the type:

  • Type II BLS: This type presents with severe combined immunodeficiency-like symptoms, including recurrent bacterial, viral, and fungal infections, chronic diarrhea, and failure to thrive.

Diagnosis

Diagnosis of bare lymphocyte syndrome involves a combination of clinical evaluation, laboratory tests, and genetic analysis. Key diagnostic tests include:

  • Flow cytometry to assess the expression of MHC molecules on lymphocytes.
  • Genetic testing to identify mutations in genes associated with MHC expression.
  • Immunological assays to evaluate the function of T-cells and other immune components.

Treatment

The treatment of bare lymphocyte syndrome is primarily supportive and may include:

Prognosis

The prognosis for patients with bare lymphocyte syndrome varies depending on the type and severity of the condition. Type I BLS generally has a better prognosis with appropriate management, while Type II BLS often requires early intervention with HSCT to improve survival outcomes.

Related pages

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