Neutrophil Dysfunction in a Family With a SAPHO Syndrome-like Phenotype

Polly J FERGUSON; Mary A LOKUTA; Hatem I EL-SHANTI; Leah MUHLE; Xinyu Bing; Anna HUTTENLOCHER

doi:10.1002/art.23942

Back

Neutrophil Dysfunction in a Family With a SAPHO Syndrome-like Phenotype

Journal article

Open access

Peer reviewed

Neutrophil Dysfunction in a Family With a SAPHO Syndrome-like Phenotype

Polly J FERGUSON, Mary A LOKUTA, Hatem I EL-SHANTI, Leah MUHLE, Xinyu Bing and Anna HUTTENLOCHER

Arthritis and rheumatism, Vol.58(10), pp.3264-3269

2008

DOI: 10.1002/art.23942

PMID: 18821685

Files and links (1)

url

https://doi.org/10.1002/art.23942View

Published (Version of record) Open Access

Abstract

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is an inflammatory disorder of the bone, skin, and joints. We describe a family with multiple affected members who segregate a SAPHO syndrome–like phenotype, and we report the results of neutrophil studies and candidate gene analysis. We obtained written informed consent and a family history and reviewed medical records. We collected DNA and sequenced candidate genes, and we performed functional studies on neutrophils isolated from the proband and her mother. The pedigree segregated chronic osteomyelitis and cutaneous inflammation in a pattern that suggested an autosomal-dominant disorder. No coding sequence mutations were detected in PSTPIP1, PSTPIP2, LPIN2, SH3BP2, or NCF4. Analysis of neutrophil function in the proband, including nitroblue tetrazolium tests, myeloperoxidase assays, neutrophil chemotaxis, and neutrophil chemotaxis assays, revealed no identifiable abnormalities. However, an abnormality in the luminol, but not the isoluminol, respiratory burst assays following stimulation with phorbol myristate acetate (PMA) was detected in neutrophils isolated from the affected proband. Internal oxidant production was also reduced in the proband and her mother when neutrophils were treated with fMLP with or without platelet-activating factor, PMA alone, or tumor necrosis factor α alone. This family segregates a disorder characterized by chronic inflammation of the skin and bone. Functional differences in neutrophils exist between affected individuals and controls. The biologic significance of this defect remains unknown. Identification of the gene defect will help identify an immunologic pathway that, when dysregulated, causes inflammation of the skin and bone.

Biological and medical sciences

Diseases of the osteoarticular system

Medical sciences

Details

Title: Subtitle: Neutrophil Dysfunction in a Family With a SAPHO Syndrome-like Phenotype
Creators: Polly J FERGUSON - University of Wisconsin, Madison, United States
Mary A LOKUTA - University of Wisconsin, Madison, United States
Hatem I EL-SHANTI - University of Wisconsin, Madison, United States
Leah MUHLE - University of Wisconsin, Madison, United States
Xinyu Bing - University of Wisconsin, Madison, United States
Anna HUTTENLOCHER - University of Wisconsin, Madison, United States
Resource Type: Journal article
Publication Details: Arthritis and rheumatism, Vol.58(10), pp.3264-3269
DOI: 10.1002/art.23942
PMID: 18821685
NLM abbreviation: Arthritis Rheum
ISSN: 0004-3591
eISSN: 1529-0131
Publisher: Wiley; Hoboken , NJ
Language: English
Date published: 2008
Academic Unit: Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984070100802771

Metrics

18 Record Views

74 Times Cited - Web of Science