Dissemin is shutting down on January 1st, 2025

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Elsevier, Clinical Immunology, 2(153), p. 288-291

DOI: 10.1016/j.clim.2014.05.001

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A novel disease-causing CD40L mutation reduces expression of CD40 ligand, but preserves CD40 binding capacity

This paper is available in a repository.
This paper is available in a repository.

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Data provided by SHERPA/RoMEO

Abstract

Mutations in CD40 ligand (CD40L) that permit residual CD40L expression typically impair binding of CD40. We report a male patient who presented with recurrent bacterial respiratory tract infections, normal IgM, decreased IgG, absent IgA levels, and CD40L expression at ~50% of the level observed in the normal control. He subsequently developed autoimmunity, inflammatory bowel disease, severe opportunistic infections suggestive of a combined immunodeficiency, and a cervical spine schwannoma. Whole exome sequencing of the patient's genomic DNA revealed a novel missense mutation (p.H47Y) in CD40L. Although this mutation was predicted to be benign in silico, flow cytometry at 13years of age demonstrated markedly decreased CD40L expression (~32% of normal control) that retained the capacity to bind soluble CD40-Ig, suggesting that the mutation impairs CD40L surface expression without affecting its affinity for CD40. This case highlights the variability in the clinical evolution and phenotype of CD40L deficiency.