Bare lymphocyte syndrome (BLS) is a rare inherited disorder that affects the immune system. Individuals with BLS experience a compromised immune response, making them susceptible to severe and recurrent illnesses.
Understanding Bare Lymphocyte Syndrome
The immune system relies on specialized white blood cells called lymphocytes, which include T-cells and B-cells, to identify and eliminate threats. These cells use specific molecules on their surface, known as Major Histocompatibility Complex (MHC) molecules, to recognize fragments of foreign invaders, called antigens. MHC Class I molecules are found on almost all cells and present internal antigens, while MHC Class II molecules are primarily on specialized immune cells and present external antigens.
In bare lymphocyte syndrome, the “bare” refers to the absence or significant reduction of these MHC molecules on the surface of immune cells. Without these crucial molecules, lymphocytes cannot properly recognize and respond to pathogens.
Genetic Roots and Categories
Bare lymphocyte syndrome is a genetic condition. It follows an autosomal recessive inheritance pattern, meaning a child must inherit a mutated copy of the specific gene from both parents to develop the syndrome. Parents who carry one copy of the mutated gene do not show symptoms themselves.
The syndrome results from mutations in genes responsible for producing or regulating MHC Class I or MHC Class II molecules. There are two primary types of BLS. Type I, or MHC Class I deficiency, is linked to mutations in genes such as TAP1 or TAP2, which are involved in transporting antigen fragments for MHC Class I presentation. Type II, or MHC Class II deficiency, is generally more severe and is caused by mutations in regulatory genes like CIITA, RFXANK, RFXAP, or RFX5, which control the expression of MHC Class II genes.
Recognizing the Symptoms
The symptoms of bare lymphocyte syndrome primarily arise from a severely weakened immune system. Individuals experience recurrent, severe, and opportunistic infections, which are illnesses caused by germs that do not affect healthy people. These infections can include bacterial, viral, fungal, and parasitic pathogens.
Commonly affected areas include the respiratory tract, leading to frequent pneumonia, bronchitis, and sinus infections. The gastrointestinal tract is also impacted, resulting in chronic diarrhea, malabsorption of nutrients, and a failure to gain weight and grow properly. Skin infections that do not respond well to standard treatments can also occur. Symptoms begin early in life, during infancy or early childhood, and their severity can vary depending on the specific type of BLS.
How Bare Lymphocyte Syndrome Is Diagnosed
Diagnosis of bare lymphocyte syndrome begins with a doctor’s suspicion based on a child’s history of recurrent and severe infections. Initial blood tests may reveal abnormalities in immune cell counts or unusual immune responses. For instance, individuals with Type II BLS have decreased levels of CD4+ T-cells, a type of helper lymphocyte.
Flow cytometry, a laboratory technique, measures the presence or absence of MHC Class I or Class II molecules on the surface of lymphocytes. This test confirms if these molecules are missing or present at very low levels. Genetic testing is then performed to identify the specific gene mutations responsible for the condition, providing a definitive diagnosis.
Treatment Options and Prognosis
Treatment for bare lymphocyte syndrome primarily focuses on managing and preventing infections, as the immune system is compromised. This involves the long-term use of antibiotics, antifungals, and antiviral medications to combat ongoing and potential infections. These supportive therapies aim to control the immediate effects of the immune deficiency.
The only potentially curative treatment for bare lymphocyte syndrome, especially for Type II, is hematopoietic stem cell transplantation (HSCT), commonly known as a bone marrow transplant. This procedure involves replacing the patient’s defective immune system cells with healthy stem cells from a compatible donor, which then produce functional immune cells. Early diagnosis and prompt transplantation can significantly improve outcomes. Without a successful transplant, the prognosis for individuals with severe forms of BLS, particularly Type II, is poor, often leading to early death due to overwhelming infections. With a successful transplant, individuals can lead healthier lives, though continued medical monitoring is necessary.