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

GUNAYDIN N. C. , Chou J., KARACA N. , AKSU G. , Massaad M. J. , AZARSIZ E. , ...More

CLINICAL IMMUNOLOGY, vol.153, no.2, pp.288-291, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 153 Issue: 2
  • Publication Date: 2014
  • Doi Number: 10.1016/j.clim.2014.05.001
  • Title of Journal : CLINICAL IMMUNOLOGY
  • Page Numbers: pp.288-291


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 similar to 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 patients genomic DNA revealed a novel missense mutation (p.H47Y) in CD40L. Although this mutation was predicted to be benign in silico, flow cytometry at 13 years of age demonstrated markedly decreased CD40L expression (similar to 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. (C) 2014 Elsevier Inc. All rights reserved.