Serum sBCMA in primary and secondary antibody deficiency.
Bagkou Dimakou, Danai Peters, Nicholas E Burns, Siobhan O Richter, Alex G Shields, Adrian M
Bagkou Dimakou, Danai
Peters, Nicholas E
Burns, Siobhan O
Richter, Alex G
Shields, Adrian M
Affiliation
Royal Free London NHS Foundation Trust; University College London; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham
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Publication date
2025-09-29
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Abstract
BACKGROUND: B-cell maturation antigen (BCMA) is a B cell surface receptor that regulates activation, proliferation and survival. BCMA can be cleaved from the cell surface, producing soluble BCMA (sBCMA), which has been studied as a disease biomarker in systemic lupus erythematosus, multiple sclerosis and multiple myeloma. Reduced sBCMA concentrations have been associated with the severity of different primary antibody deficiencies.
AIMS AND METHODS: We explored the relationship between sBCMA concentrations, humoral immune responses to SARS-CoV-2 vaccination and disease complications in 107 individuals with primary and secondary antibody deficiency enrolled in the COVID-19 in Antibody Deficiency (COV-AD) study.
RESULTS: Serum sBCMA concentrations were significantly reduced in primary antibody deficiencies compared to healthy controls and asymptomatic selective IgA deficiency. Individuals with X- linked agammaglobulinemia and common variable immunodeficiency (CVID) demonstrated the lowest serum concentrations of sBCMA. sBCMA concentrations in secondary antibody deficiency were highly variable. Amongst individuals with CVID, peripheral blood CD19 count, but not sBCMA concentrations discriminated SARS-CoV-2 vaccine responders. sBCMA was significantly lower in individuals with CVID and bronchiectasis and outperformed serum IgA and IgM concentrations in discriminating this subgroup. sBCMA was not associated with any other complication of CVID.
CONCLUSION: Our data highlights the potential of sBCMA as biomarker to support the assessment of antibody deficiency. In primary antibody deficiencies, it may contribute to the risk stratification of disease severity and identify those at risk of bronchiectasis. In secondary antibody deficiency, it may identify subgroups that would benefit from intensive monitoring and therapy.
Citation
Bagkou Dimakou D, Peters NE, Burns SO, Richter AG, Shields AM. Serum sBCMA in primary and secondary antibody deficiency. Clin Exp Immunol. 2025 Sep 29:uxaf065. doi: 10.1093/cei/uxaf065. Epub ahead of print.
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Article