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

    Research output: Contribution to journalArticle

    64 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)3264-3269
    Number of pages6
    JournalArthritis and Rheumatism
    Issue number10
    Publication statusPublished - 1 Oct 2008


    ASJC Scopus subject areas

    • Immunology and Allergy
    • Rheumatology
    • Immunology
    • Pharmacology (medical)

    Cite this

    Ferguson, P. J., Lokuta, M. A., El-Shanti, H. I., Muhle, L., Bing, X., & Huttenlocher, A. (2008). Neutrophil dysfunction in a family with a SAPHO syndrome-like phenotype. Arthritis and Rheumatism, 58(10), 3264-3269.