Long-term follow-up on affinity maturation and memory B-cell generation in patients with common variable...

Area of Science:

• Immunology
• Clinical Medicine

Background:

• Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency.
• Immunophenotyping of memory B cells and somatic hypermutation (SHM) levels are used for CVID classification and prognosis.
• Diagnostic delays are common in CVID, necessitating evaluation of classification parameter stability.

Purpose of the Study:

• To assess the long-term stability of immunologic classification markers in Common variable immunodeficiency (CVID) patients.
• To determine if EUROclass criteria and somatic hypermutation (SHM) levels remain consistent over time after diagnosis.
• To investigate the relationship between clinical manifestations and these immunologic markers in a CVID cohort.

Main Methods:

• Flow cytometric immunophenotyping was used to analyze class-switched memory B cells.
• EUROclass criteria were applied for patient classification.
• Somatic hypermutation (SHM) levels were measured using Igκ-REHMA.
• Clinical data including splenomegaly, autoimmune disease, and granulomatous disease were collected.

Main Results:

• Switched memory B cells and SHM levels demonstrated inconsistent stability in long-term follow-up.
• While 60% of patients met the SmB- EUROclass criteria at some point, only 23% remained consistently classified.
• No significant associations were found between clinical manifestations and switched memory B cell levels or SHM.

Conclusions:

• Immunologic markers used for CVID classification are not consistently stable over extended periods.
• Repeated immunologic assessments using standardized methods are recommended after CVID diagnosis.
• Current classification parameters may require re-evaluation to ensure long-term prognostic accuracy.