Bare lymphocyte syndrome 2

Other Names: Bare lymphocyte syndrome type 2; BLS 2; Severe combined immunodeficiency, HLA class ii-negative; SCID, HLA Class 2-Negative

Bare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined immunodeficiency (CID). People with BLS II lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system.

Epidemiology

BLS II is a rare condition. At least 100 cases have been reported in the medical literature. While BLS II has been found in several populations throughout the world, it appears to be especially prevalent in the Mediterranean region and North Africa.

Cause

BLS II is caused by mutations in the CIITA, RFX5, RFXANK, or RFXAP gene. Each of these genes provides instructions for making a protein that plays a role in controlling the activity (transcription) of genes called MHC class II genes. Transcription is the first step in the production of proteins, and the CIITA, RFX5, RFXANK, and RFXAP proteins are critical for the production of MHC class II proteins from these genes.

The RFX5, RFXANK, and RFXAP proteins come together to form the regulatory factor X (RFX) complex, which attaches (binds) to specific regions of DNA involved in the regulation of MHC class II gene activity. The CIITA protein interacts with the RFX complex and brings together other proteins that turn on gene transcription, leading to the production of MHC class II proteins.

MHC class II proteins play an important role in the body's immune response to foreign invaders, such as bacteria, viruses, and fungi. To help the body recognize and fight infections, MHC class II proteins on lymphocytes bind to fragments of proteins (peptides) from foreign invaders so that other specialized immune system cells can interact with them. When these immune system cells recognize the peptides as harmful, they trigger the lymphocytes to launch immune responses to get rid of the foreign invaders.

Mutations in the CIITA, RFX5, RFXANK, or RFXAP gene prevent transcription of MHC class II genes, which leads to an absence of MHC class II proteins on the surface of certain lymphocytes. Lack of these proteins on lymphocytes impairs the body's immune response to bacteria, viruses, and fungi, leading to persistent infections in individuals with BLS II syndrome.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

BLS II is typically diagnosed in the first year of life. Most affected infants have persistent infections in the respiratory, gastrointestinal, and urinary tracts. Because of the infections, affected infants have difficulty absorbing nutrients (malabsorption), and they grow more slowly than their peers. Eventually, the persistent infections lead to organ failure. Without treatment, individuals with BLS II usually do not survive past early childhood.

In people with BLS II, infection-fighting white blood cells (lymphocytes) are missing specialized proteins on their surface called major histocompatibility complex (MHC) class II proteins, which is where the condition got its name. Because BLS II is the most common and best studied form of a group of related conditions, it is often referred to as simply bare lymphocyte syndrome (BLS).

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 100% of people have these symptoms

• Reduced MHC II surface expression

80%-99% of people have these symptoms

• Lack of T cell function
• Recurrent infection of the gastrointestinal tract(Recurrent gastrointestinal infections)
• Recurrent respiratory infections(Frequent respiratory infections)

30%-79% of people have these symptoms

• Chronic hepatitis due to cryptosporidium infection
• Chronic mucocutaneous candidiasis
• Decreased circulating beta-2-microglobulin level
• Decreased proportion of CD4-positive helper T cells
• Failure to thrive(Faltering weight)
• Protracted diarrhea
• Recurrent candida infections
• Recurrent herpes(Susceptibility to herpesvirus)
• Recurrent protozoan infections
• Recurrent Staphylococcus aureus infections
• Rhinitis(Nasal inflammation)
• Sclerosing cholangitis
• Sinusitis(Sinus inflammation)

5%-29% of people have these symptoms

• Abnormal CD4:CD8 ratio
• Acute otitis media(Acute middle ear infection)
• Autoimmune hemolytic anemia
• Autoimmune thrombocytopenia
• Decreased lymphocyte proliferation in response to mitogen
• Neutropenia in presence of anti-neutropil antibodies
• Pancytopenia(Low blood cell count)
• Panhypogammaglobulinemia
• Skin rash

1%-4% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Dysarthria(Difficulty articulating speech)
• Gait ataxia(Inability to coordinate movements when walking)

Diagnosis

The diagnosis for Bare lymphocyte syndrome type II can be done via genetic testing. A blood test could indicate decreased CD4+ T-cells(T-helper lymphocyte), as well as serum immunoglobulin.

Treatment

In terms of treatment for major histocompatibility complex class II deficiency(Bare lymphocyte syndrome type II), one finds that according to Matheux, et al. a possible treatment for this condition might be found in cellular and gene therapy.The prognosis is poor (without treatment) in early childhood for this condition; additional treatment options include anti-microbial prophylaxis prior to bone marrow transplant.

NIH genetic and rare disease info

• NIH info on Bare lymphocyte syndrome 2

Bare lymphocyte syndrome 2 is a rare disease.

Bare lymphocyte syndrome 2 Resources
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