A 25-year-old man with recurrent pyogenic infections by encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae) since infancy is found to have absent B cells and profoundly low immunoglobulins of all isotypes. T cells are normal. What is the molecular defect in X-linked agammaglobulinemia (Bruton's disease)?
- A Absent adenosine deaminase (ADA) leading to toxic accumulation of deoxyadenosine in lymphoid precursors
- B Defect in Bruton tyrosine kinase (BTK) arresting B cell maturation at the pre-B cell stage ✓
- C Absent CD40L on T cells preventing isotype class switching and germinal center formation
- D MHC class II deficiency preventing CD4+ T cell activation and B cell help
Explanation
X-linked agammaglobulinemia (Bruton's disease) results from mutations in the BTK gene encoding Bruton tyrosine kinase, a signalling kinase essential for B cell receptor (pre-BCR) signalling during B lymphocyte maturation. Without functional BTK, B cell development arrests at the pre-B cell stage in the bone marrow, resulting in absent circulating mature B cells and profoundly low immunoglobulins of all classes. ADA deficiency causes SCID affecting both T and B cells; CD40L deficiency causes hyper-IgM syndrome with normal/elevated IgM but absent IgG/IgA/IgE; MHC II deficiency causes a form of combined immunodeficiency.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.