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X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis.
J Clin Immunol. 2016 08; 36(6):564-70.JC

Abstract

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.

Authors+Show Affiliations

Division of Asthma, Department of Pediatrics, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.Division of Asthma, Department of Pediatrics, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.Division of Asthma, Department of Pediatrics, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, WA, USA.Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, WA, USA.Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, WA, USA.Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.Division of Asthma, Department of Pediatrics, Allergy and Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA. jroutes@mcw.edu.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

27324886

Citation

Gallagher, Joel, et al. "X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis." Journal of Clinical Immunology, vol. 36, no. 6, 2016, pp. 564-70.
Gallagher J, Adams J, Hintermeyer M, et al. X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis. J Clin Immunol. 2016;36(6):564-70.
Gallagher, J., Adams, J., Hintermeyer, M., Torgerson, T. R., Lopez-Guisa, J., Ochs, H. D., Szabo, S., Salib, M., Verbsky, J., & Routes, J. (2016). X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis. Journal of Clinical Immunology, 36(6), 564-70. https://doi.org/10.1007/s10875-016-0307-0
Gallagher J, et al. X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis. J Clin Immunol. 2016;36(6):564-70. PubMed PMID: 27324886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - X-linked Hyper IgM Syndrome Presenting as Pulmonary Alveolar Proteinosis. AU - Gallagher,Joel, AU - Adams,Juan, AU - Hintermeyer,Mary, AU - Torgerson,Troy R, AU - Lopez-Guisa,Jesus, AU - Ochs,Hans D, AU - Szabo,Sara, AU - Salib,Mina, AU - Verbsky,James, AU - Routes,John, Y1 - 2016/06/20/ PY - 2016/02/15/received PY - 2016/06/03/accepted PY - 2016/6/22/entrez PY - 2016/6/22/pubmed PY - 2017/12/8/medline KW - CD40 ligand (CD40L) KW - Hyper IgM Syndrome KW - Macrophage dysfunction KW - Pulmonary alveolar proteinosis SP - 564 EP - 70 JF - Journal of clinical immunology JO - J. Clin. Immunol. VL - 36 IS - 6 N2 - 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. SN - 1573-2592 UR - https://www.unboundmedicine.com/medline/citation/27324886/X_linked_Hyper_IgM_Syndrome_Presenting_as_Pulmonary_Alveolar_Proteinosis_ L2 - https://doi.org/10.1007/s10875-016-0307-0 DB - PRIME DP - Unbound Medicine ER -