Alarming consequences – autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1. Issue 5 (September 2016)

• Record Type: Journal Article
• Authors: Holzinger, Dirk; Roth, Johannes
• Is Part Of: Current opinion in rheumatology. Volume 28:Issue 5(2016:Sep.)
• Publication Date: 2016-09
• Subjects: alarmins -- myeloid related proteins 8/14 -- Proline-serine-threonine phosphatase-interacting protein 1 -- Proline-serine-threonine phosphatase-interacting protein 1-associated inflammatory diseases -- pyogenic sterile arthritis, pyoderma gangrenosum, acne; Rheumatology -- Periodicals; Arthritis -- Periodicals; Review Literature -- Periodicals; Rheumatic Diseases -- Periodicals; 616.723
• DOI: 10.1097/BOR.0000000000000314
• Languages: English
• ISSNs: 1040-8711

Abstract

Abstract : 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.