X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis. J Clin Immunol 2016 Aug;36(6):564-70
Date
06/22/2016Pubmed ID
27324886DOI
10.1007/s10875-016-0307-0Scopus ID
2-s2.0-84975263201 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
PURPOSE: X-linked hyper IgM syndrome (XHIGM) is a combined immunodeficiency caused by mutations in the CD40 ligand (CD40L) gene that typically results in decreased or absent CD40L expression on activated T cells, leading to defective class switching and somatic hypermutation. We describe an infant who presented with respiratory failure due to pulmonary alveolar proteinosis (PAP) with a novel damaging missense mutation in the CD40L gene.
METHODS: Whole exome sequencing (WES) was used to identify a mutation in the CD40L gene. CD40L expression and function were determined by flow cytometry.
RESULTS: A 5-month-old previously-healthy male presented with respiratory failure and diffuse pulmonary ground glass opacities on CT scan of the chest. Laboratory evaluation revealed an undetectable IgG, normal IgA, and elevated IgM. A bronchoalveolar lavage demonstrated pulmonary alveolar proteinosis. WES demonstrated a c.608G > C mutation in the CD40L gene resulting in p.R203T. Flow cytometry demonstrated normal CD40L expression on activated T cells but absent binding of CD40-Ig to CD40L on activated patient T cells.
CONCLUSIONS: The clinical manifestations of XHIGM in our patient had several unique features, including the presentation with PAP, normal serum IgA, and expression of non-functional CD40L on activated T cells. To our knowledge, this is the first published case of PAP in a patient with XHIGM.
Author List
Gallagher J, Adams J, Hintermeyer M, Torgerson TR, Lopez-Guisa J, Ochs HD, Szabo S, Salib M, Verbsky J, Routes JAuthor
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BiomarkersCD40 Ligand
Diagnosis, Differential
Humans
Hyper-IgM Immunodeficiency Syndrome, Type 1
Infant
Lymphocyte Activation
Lymphocyte Count
Lymphocyte Subsets
Male
Mutation
Phenotype
Pulmonary Alveolar Proteinosis
Radiography, Thoracic
Tomography, X-Ray Computed
