[PMID]: | 27773721 |
[Au] Autor: | Tajerian M; Hung V; Khan H; Lahey LJ; Sun Y; Birklein F; Krämer HH; Robinson WH; Kingery WS; Clark JD |
[Ad] Endereço: | Veterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA. Electronic address: maral@stanford.edu. |
[Ti] Título: | Identification of KRT16 as a target of an autoantibody response in complex regional pain syndrome. |
[So] Source: | Exp Neurol;287(Pt 1):14-20, 2017 Jan. |
[Is] ISSN: | 1090-2430 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | OBJECTIVE: Using a mouse model of complex regional pain syndrome (CRPS), our goal was to identify autoantigens in the skin of the affected limb. METHODS: A CRPS-like state was induced using the tibia fracture/cast immobilization model. Three weeks after fracture, hindpaw skin was homogenized, run on 2-d gels, and probed by sera from fracture and control mice. Spots of interest were analyzed by liquid chromatography-mass spectroscopy (LC-MS) and the list of targets validated by examining their abundance and subcellular localization. In order to measure the autoantigenicity of selected protein targets, we quantified the binding of IgM in control and fracture mice sera, as well as in control and CRPS human sera, to the recombinant protein. RESULTS: We show unique binding between fracture skin extracts and fracture sera, suggesting the presence of auto-antigens. LC-MS analysis provided us a list of potential targets, some of which were upregulated after fracture (KRT16, eEF1a1, and PRPH), while others showed subcellular-redistribution and increased membrane localization (ANXA2 and ENO3). No changes in protein citrullination or carbamylation were observed. In addition to increased abundance, KRT16 demonstrated autoantigenicity, since sera from both fracture mice and CRPS patients showed increased autoantibody binding to recombinant kRT16 protein. CONCLUSIONS: Pursuing autoimmune contributions to CRPS provides a novel approach to understanding the condition and may allow the development of mechanism-based therapies. The identification of autoantibodies against KRT16 as a biomarker in mice and in humans is a critical step towards these goals, and towards redefining CRPS as having an autoimmune etiology. |
[Mh] Termos MeSH primário: |
Autoantígenos/metabolismo Síndromes da Dor Regional Complexa/sangue Síndromes da Dor Regional Complexa/patologia Queratina-6/imunologia Queratina-6/metabolismo Pele/metabolismo Pele/ultraestrutura Regulação para Cima/fisiologia
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[Mh] Termos MeSH secundário: |
Adulto Animais Anexina A2/metabolismo Autoantígenos/genética Modelos Animais de Doenças Membro Posterior/inervação Seres Humanos Masculino Camundongos Camundongos Endogâmicos C57BL Meia-Idade Fator 1 de Elongação de Peptídeos/metabolismo Periferinas/metabolismo Fosfopiruvato Hidratase/metabolismo Frações Subcelulares/metabolismo Fraturas da Tíbia/sangue Fraturas da Tíbia/patologia Adulto Jovem
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (ANXA2 protein, human); 0 (Annexin A2); 0 (Autoantigens); 0 (EEF1A1 protein, human); 0 (KRT6A protein, human); 0 (Keratin-6); 0 (PRPH protein, human); 0 (Peptide Elongation Factor 1); 0 (Peripherins); EC 4.2.1.11 (Phosphopyruvate Hydratase) |
[Em] Mês de entrada: | 1705 |
[Cu] Atualização por classe: | 180101 |
[Lr] Data última revisão:
| 180101 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161028 |
[St] Status: | MEDLINE |
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