Alarming consequences - autoinflammatory disease spectrum due to mutations in proline-serine-threonine phosphatase-interacting protein 1.
Curr Opin Rheumatol
; 28(5): 550-9, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27464597
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
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Artritis Infecciosa
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Piodermia Gangrenosa
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Acné Vulgar
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Transportadoras de Casetes de Unión a ATP
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Interleucina-1beta
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Enfermedades Autoinflamatorias Hereditarias
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Alarminas
Límite:
Humans
Idioma:
En
Revista:
Curr Opin Rheumatol
Asunto de la revista:
REUMATOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania