Bare lymphocyte syndrome

Overview

Bare lymphocyte syndrome (BLS) is a group of rare, inherited primary immunodeficiency disorders characterized by a lack or severe reduction ofmajor histocompatibility complex (MHC) moleculeson the surface of immune cells. This defect disrupts the immune system’s ability to recognize and respond to pathogens, leading to severe, recurrent infections. BLS is categorized into different types based on which class of MHC molecule is affected:

• Type I – deficiency of MHC class I molecules

• Type II – deficiency of MHC class II molecules (more severe)

• Combined types are extremely rare

BLS is considered a form ofsevere combined immunodeficiency (SCID)and often presents in infancy.

Causes

Bare lymphocyte syndrome is caused bygenetic mutationsthat impair the expression of MHC molecules, which are essential for activating T cells.

• Type I BLS – caused by mutations in genes such as TAP1, TAP2, or TAPBP, which are involved in antigen processing for MHC class I

• Type II BLS – caused by mutations in regulatory genes such as CIITA, RFX5, RFXAP, or RFXANK, which are essential for MHC class II transcription

• Inheritance pattern – autosomal recessive (both parents must carry a defective gene)

Symptoms

Symptoms of BLS vary depending on the type, with BLS type II being more severe than type I.Common symptoms include:

• Recurrent, severe infections (bacterial, viral, fungal, or parasitic)

• Chronic diarrhea

• Failure to thrive in infancy

• Enlarged lymph nodes and spleen

• Low T cell function (especially CD4+ cells in type II)

• Skin rashes or dermatitis

• Delayed or absent response to vaccines

Diagnosis

Early diagnosis is critical due to the life-threatening nature of the disease. Evaluation includes:

• Complete blood count (CBC) – may show lymphopenia (especially CD4+ cells in type II)

• Flow cytometry – used to detect absence of MHC I or II on the surface of white blood cells

• Genetic testing – confirms the type of BLS and identifies the mutated gene

• Immunoglobulin levels – often reduced

• Family history – especially in consanguineous families

Treatment

There is no definitive cure for BLS except for hematopoietic stem cell transplantation (HSCT), especially for type II. Supportive and preventive care is essential.

• Hematopoietic stem cell transplant (HSCT) – curative if done early, especially in type II BLS

• Antibiotic prophylaxis – to prevent bacterial infections

• Antifungal and antiviral medications – to reduce infection risks

• Immunoglobulin replacement therapy – to support humoral immunity

• Nutritional and supportive care – to manage complications and growth issues

Prognosis

The prognosis for bare lymphocyte syndrome depends on the type, severity, and timing of diagnosis and treatment:

• BLS type I – typically milder, with some patients surviving into adulthood with chronic infections

• BLS type II – severe and often fatal in early childhood without HSCT

• Early HSCT can dramatically improve outcomes and survival

• Ongoing care is essential to manage infections and immune deficiency

Early detection and treatment offer the best chance for improved survival and quality of life.