Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice

Liao, Hua‐Fang; Chyuan, I‐Tsu; Wu, Chien-Sheng; Lin, Shi‐Ming; Chen, Kun-Hung; Tsai, Hwei-Fang; Hsu, Ping–I

doi:10.1093/rheumatology/keu481

Cited by 30 publications

(13 citation statements)

References 36 publications

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“…Circulating neutrophils are very sensitive to inflammatory signals and are the first pioneers recruited to the inflammatory site [13]. Besides, enhanced neutrophil infiltration was observed in mice with a SAPHO syndrome-like phenotype [10]. In this study, RNA-Seq was performed to profile the mRNA expression level of neutrophils purified from peripheral blood of SAPHO patients.…”

Section: Discussionmentioning

confidence: 99%

“…As for the largest population of innate immune cells, neutrophils, existing evidence has been limited. Although enhanced neutrophil infiltration was observed in PSTPIP2-deficient mice which presented a SAPHO syndrome-like phenotype [10], no significant increase in serum neutrophils in patients had been found. Neutrophils purified from patients with SAPHO syndrome were reported to have an abnormal internal oxidant production following stimulation with phorbol myristate acetate (PMA) [11], but no signs of aberrant intercellular oxidant production was shown [12].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Sun

Zhu

et al. 2019

Orphanet J Rare Dis

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Background SAPHO syndrome is a rare disease characterized by inflammatory lesions on skin and bones. Diversified manifestation and inadequate understanding of etiology has limited its diagnosis and treatment. The co-occurrence of other immune-mediated diseases strongly suggests an involvement of autoimmunity in SAPHO syndrome. However, the role of the largest population of circulating immune cells, neutrophils, is still not well explored. In this study, we performed RNA sequencing to profile the mRNA expression of neutrophils purified from peripheral blood of SAPHO patients to identify key genes associated with SAPHO syndrome, trying to find new functional molecules or biomarkers for this rare disease. Results A total of 442 differentially expressed genes were identified ( p < 0.05, fold change > 2), in which 294 genes were upregulated and 148 genes were downregulated. Five differentially expressed genes of interest were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), among which S100A12 was upregulated and positively related to high-sensitivity C-reactive protein (hsCRP), while the downregulated gene MYADM was positively related to osteocalcin. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes were enriched in “systemic lupus erythematosus” and “ECM-receptor interaction”. Gene ontology (GO) enrichment showed that differentially expressed genes may participate in biological processes such as “cell migration” and “cell adhesion”. Conclusions In conclusion, this study provides a first insight into transcriptome characteristics of SAPHO syndrome, indicating an over-active neutrophil recruitment in patients and possibly suggesting molecular candidates for further study on diagnosis and pathology of this disease. Electronic supplementary material The online version of this article (10.1186/s13023-019-1169-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Sun

Zhu

et al. 2019

Orphanet J Rare Dis

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“…Whereas, in our population, underdiagnosis of IBD cannot be excluded, intestinal manifestations in SCCH patients, albeit non-specific, may also represent an independent inflammatory phenomenon outside the context of IBD. Recent insights from the Pstpip2 -deficient mouse model suggest that this is plausible [ 34 , 35 ]. In these osteomyelitis-susceptible mice, alterations in the intestinal microbiota were thus found to accompany manifestations of inflammatory bone disease.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of autoimmune disease in the rare inflammatory bone disorder sternocostoclavicular hyperostosis: survey of a Dutch cohort

Valkema

Luymes

Witteveen

et al. 2017

Orphanet J Rare Dis

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BackgroundSternocostoclavicular hyperostosis (SCCH; ORPHA178311) is a rare inflammatory disorder of the axial skeleton, the precise pathophysiology of which remains to be established. We addressed the potential association of SCCH with autoimmune processes by evaluating the lifetime prevalence of autoimmune disease in 70 patients with adult-onset SCCH and 518 SCCH-unaffected first-degree relatives (parents, siblings and children). Danish hospital registry data for autoimmune diseases were used as reference data.ResultsThe mean age of interviewed patients was 56.3 years (range 26–80 years) and 86% were female. Interviewed patients belonged to 63 families, with four families having clusters of 2–3 patients. A diagnosis of at least one autoimmune disease was reported in 20 SCCH patients (29%) and in 47 relatives (9.1%), compared to an estimated 3.9% prevalence of autoimmune disease in the Danish reference population. A diversity of autoimmune diseases was reported in SCCH patients and relatives, most frequently psoriasis vulgaris (14%). Palmoplantar pustulosis was reported by 28 patients (40%). In SCCH patients, inclusion of palmoplantar pustulosis as putative autoimmune disease increased the overall prevalence to 54%.ConclusionsThe high prevalence of autoimmune disease in patients with sternocostoclavicular hyperostosis and their first-degree relatives suggests that autoimmunity may play a role in the still elusive pathophysiology of the intriguing osteogenic response to inflammation observed in this rare bone disorder.

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“…Chronic multifocal osteomyelitis ( cmo ) mice carry a spontaneously acquired homozygous mutation (c.T293C, p.L98P) in Pstpip2 . To date, the exact molecular contribution of Pstpip2 mutations to sterile bone inflammation remains somewhat unclear [ 57 ]. Pstpip2 belongs to the F-BAR (Fes/CIP4 homology-Bin/Amphiphysin/Rvs) domain containing protein superfamily, which couples membrane remodeling with actin dynamics associated to endocytic pathways and filopodium formation [ 58 ].…”

Section: Murine Models Of Crmomentioning

confidence: 99%

Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment

Hofmann

Kapplusch

Girschick

et al. 2017

Curr Osteoporos Rep

194

207

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Purpose of ReviewChronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO.Recent FindingsThough the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues.SummaryCNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.

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Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice

Abstract: Our study suggests that PSTPIP2 could play a role in innate immunity and development of autoinflammatory bone disorders, and may be associated with the pathogenesis of human SAPHO syndrome.

Cited by 30 publications

References 36 publications

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq

High prevalence of autoimmune disease in the rare inflammatory bone disorder sternocostoclavicular hyperostosis: survey of a Dutch cohort

Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment

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