Splicing factor proline/glutamine-rich is a novel autoantigen of dermatomyositis and associated with anti-melanoma differentiation-associated gene 5 antibody.
J Autoimmun
; 77: 116-122, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-27919567
ABSTRACT
OBJECTIVE:
Anti-MDA5 antibody positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop into rapidly progressive interstitial lung disease, but their pathogenesis remains unclear. We observed that sera from DM/CADM patients immunoprecipitated a common 110 kDa polypeptide. We investigated this autoantigen and its clinical significance.METHODS:
Autoantibodies were screened in 333 patients with various connective tissue diseases (CTDs) and 20 healthy controls (HCs) by immunoprecipitation with [35S]methionine-labeled HeLa cells. Immunoabsorbent column chromatography was used to purify the reactive autoantigen which was subsequently analyzed by peptide mass fingerprinting.RESULTS:
Anti-110 kDa antibody was detected in sera from 27 DM/CADM patients, but not in sera from other CTD patients or HCs. All patients with anti-110 kDa antibody had anti-MDA5 antibody. The maximum KL-6 levels in anti-110 kDa antibody-positive patients were higher than in anti-110 kDa antibody-negative patients, and all anti-MDA5-antibody-positive patients who showed the recurrence of DM/CADM were anti-110 kDa antibody-positive. The corresponding autoantigen was identified as splicing factor proline/glutamine-rich protein (SFPQ). In some cases, anti-SFPQ antibody was detected at diagnosis (early-detected group), but in other cases, it appeared during the disease course (delayed-detected group). The diagnosis timing of DM/CADM showed seasonal patterns according to the timing of anti-SFPQ antibody appearance. Specifically, 77% (10/13) of patients were diagnosed between August and October in the early-detected group, while 57% (8/14) of patients were diagnosed between January and March in the delayed-detected group.CONCLUSIONS:
Some anti-MDA5 antibody-positive patients had an antibody to SFPQ, which is known to play a role in innate immune responses. Anti-SFPQ antibody may be involved in the chronic disease course of DM/CADM. The diagnosis timing of DM/CADM in anti-MDA5 antibody-positive patients showed seasonal patterns according to the timing of anti-SFPQ antibody appearance. These findings may provide new insights into the pathogenesis of DM/CADM.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Autoantígenos
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Dermatomiositis
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Helicasa Inducida por Interferón IFIH1
/
Factor de Empalme Asociado a PTB
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2017
Tipo del documento:
Article