Alarming consequences - autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1.

Purpose Of Review: To give an overview about the expanding spectrum of autoinflammatory diseases due to mutations in proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) and new insights into their pathogenesis.Recent Findings: In addition to classical pyogenic sterile arthritis, pyo...

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Publicado en:Current Opinion in Rheumatology Vol. 28; no. 5; pp. 550 - 560
Autores principales: Holzinger, Dirk, Roth, Johannes
Formato: review Journal Article
Publicado: Lippincott Williams & Wilkins Sep2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Sep2016
      vid: 28
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      pub: Lippincott Williams & Wilkins
      place: Baltimore, Maryland
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        atl: Alarming consequences - autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1.
      aug:
        au:
          Holzinger, Dirk
          Roth, Johannes
        affil: Department of Paediatric Rheumatology and Immunology, University Children's Hospital
      sug:
        subj:
          Arthritis, Infectious Immunology
          Acne Vulgaris Immunology
          Carrier Proteins Immunology
          Pyoderma Gangrenosum Immunology
          Monocytes Immunology
          Hereditary Autoinflammatory Diseases Immunology
          Interleukin 1 Immunology
          Immunosuppressive Agents Therapeutic Use
          Tumor Necrosis Factor Antagonists and Inhibitors
          Glucocorticoids Therapeutic Use
          Cyclosporine Therapeutic Use
          Cytoskeletal Proteins
          Pyoderma Gangrenosum Drug Therapy
          Immunity Immunology
          Hereditary Autoinflammatory Diseases Drug Therapy
          Arthritis, Infectious
          Prednisolone Therapeutic Use
          Calcium Binding Proteins Immunology
          Acne Vulgaris
          Mutation
          Proteins Therapeutic Use
          Acne Vulgaris Drug Therapy
          Arthritis, Infectious Drug Therapy
          Pyoderma Gangrenosum
          Syndrome
          Hereditary Autoinflammatory Diseases
          Phenotype
          Carrier Proteins
          Antibodies, Monoclonal Therapeutic Use
          Arthritis Impact Measurement Scales
          Impact of Events Scale
          Questionnaires
          Scales
      ab: Purpose Of Review: To give an overview about the expanding spectrum of autoinflammatory diseases due to mutations in proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) and new insights into their pathogenesis.Recent Findings: In addition to classical pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome has been described as a distinct clinical phenotype of PSTPIP1-associated inflammatory diseases (PAID) and other entities are emerging. In addition to dysregulation of IL-1ß release from activated PAPA monocytes that requires NLR family, pyrin domain containing 3 (NLRP3), PSTPIP1 mutations have an general impact on cellular dynamics of cells of the innate immune system. In addition, overwhelming expression and release of the alarmins myeloid-related protein (MRP) 8 and 14 by activated phagocytes and keratinocytes, which promote innate immune mechanisms in a Toll like receptor (TLR) 4-dependent manner, are a characteristic feature of these diseases and form a positive feed-back mechanism with IL-1ß.Summary: Autoinflammatory diseases due to PSTPIP1 mutations are not restricted to the classical PAPA phenotype but might present with other distinct clinical features. MRP8/14 serum levels are a hallmark of PAPA and PAMI and can be used as screening tool to initiate targeted genetic testing in suspected cases. The feedback mechanism of IL-1ß and MRP-alarmin release may offer novel targets for future therapeutic approaches.
      pubtype: Academic Journal
      doctype:
        review
        Journal Article
      ougenre: Article
    language: English
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