Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara

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Abstract

Introduction

Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico.

Methods

Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using ³⁵S-methionine labeled K562 cell extract. Clinical information was obtained from medical records.

Results

DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% ( P = 0.0012) whereas anti-p155/140 was 9% versus 35% ( P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM ( n = 30) versus anti-Mi-2 (-) DM ( n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group ( P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy.

Conclusions

Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production.

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Most cited references 24

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The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.

Yi Zhang, Gary LeRoy, Hans-Peter Seelig … (1998)

Histone acetylation and deacetylation were found to be catalyzed by structurally distinct, multisubunit complexes that mediate, respectively, activation and repression of transcription. ATP-dependent nucleosome remodeling, mediated by different multisubunit complexes, was thought to be involved only in transcription activation. Here we report the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contains the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2beta, a polypeptide related to the metastasis-associated protein 1, and a novel polypeptide of 32 kDa. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis.

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A novel autoantibody to a 155-kd protein is associated with dermatomyositis.

B Koneru, D. O’Hanlon, … (2006)

In polymyositis and dermatomyositis (DM), identified autoantibodies occur in <50% of adult patients and in a smaller proportion of children. This study was undertaken as part of a larger effort to define novel autoantibodies that assist in the clinical evaluation of myositis. Sera from children and adults satisfying criteria for idiopathic inflammatory myopathies and from patients with other connective tissue diseases (CTDs), patients with noninflammatory myopathies, and healthy individuals were tested for autoantibodies by immunoprecipitation (IP). A previously unrecognized autoantibody that immunoprecipitated a 155-kd protein along with a weaker 140-kd protein was seen. When the presence of this anti-p155 autoantibody in test sera was suggested based on IP results, it was confirmed by immunoblotting of immunoprecipitates. Sera from 51 of 244 myositis patients (21%), including 30 with juvenile DM (29%), 5 with juvenile CTD-associated myositis (33%), 8 with adult DM (21%), 6 with cancer-associated DM (75%), and 2 with adult CTD-associated myositis (15%), were found to have anti-p155 autoantibody. One of 49 patients with lupus, and none of 89 others without myositis, had anti-p155. Caucasian patients with anti-p155 had a unique HLA risk factor, DQA1*0301 (odds ratio 5.4, corrected P = 0.004). In adults with anti-p155, of several clinical features assessed only the frequency of V-sign rash was increased, but patients with this antibody were clinically distinct from those with autoantibodies to aminoacyl-transfer RNA synthetases. A newly recognized autoantibody, anti-p155, is associated with DM and cancer-associated DM, and is one of the most common autoantibodies in this condition, occurring as frequently in children as in adults. The clinical features and immunogenetics associated with anti-p155 differ from those associated with antisynthetases.

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A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.

M. FRASER, Tommy Love, M. Dalakas … (1991)

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.

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Author and article information

Contributors

Marcelo H Petri

Minoru Satoh

Beatriz T Martin-Marquez

Raul Vargas-Ramírez

Luis J Jara

Miguel A Saavedra

Claudia Cruz-Gonzalez

Lilia Andrade-Ortega

Olga Vera-Lastra

Mario Salazar-Páramo

Rosa E Prieto-Parra

Laura Gonzalez-Lopez

Jorge I Gamez-Nava

Hermes U Ramírez-Sánchez

Jason YF Chan

Steven J Ross

Edward KL Chan

Mónica Vázquez-Del Mercado

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Print): 2013

Publication date (Electronic): 4 April 2013

Volume: 15

Issue: 2

Page: R48

Affiliations

[1 ]Departamento de Biología Molecular y Genómica, Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), Sierra Mojada 950, Planta baja, Edificio P Ala oriente, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, CP 44340 Mexico

[2 ]Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610-0221, USA

[3 ]Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610-0221, USA

[4 ]Direction of Education and Research, Hospital de Especialidades Centro Médico La Raza, IMSS, Calzada Vallejo y Jacarandas S/N, Mexico City, CP 02990, Mexico

[5 ]Servicio de Reumatología, Hospital La Raza, IMSS, Cd. de México, Calzada Vallejo y Jacarandas S/N, CP 02990, Mexico

[6 ]Centro Médico Nacional 20 de Noviembre, ISSSTE, Felix Cuevas 540 Del Valle 03100, D.F., México

[7 ]División de Medicina Interna, Hospital La Raza, IMSS, Cd de México, Calzada Vallejo y Jacarandas S/N, CP 02990, Mexico

[8 ]División de Investigación, CMNO, IMSS, Departamento de Fisiología del Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Av. Belisario Domínguez 1000, SL. Guadalajara, JL 44349, Mexico

[9 ]Servicio de Reumatología, CMNO, IMSS, Av. Belisario Dominguez 1000, Guadalajara, JL 44349, Mexico

[10 ]Servicio de Medicina Interna Reumatología, Hospital General Regional 110, IMSS, Prolongacion Circunvalacion Oblatos 2208 Guadalajara, Jalisco, CP 44700, Mexico

[11 ]UMAE, CMNO, IMSS, Guadalajara, Guadalajara, Jalisco, Av. Belisario Dominguez 1000, CP 44349, Mexico

[12 ]Instituto de astronomia y Meteorologia, Departamento de Fisica. Division de Ciencias Basicas, Universidad de Guadalajara, Av. Vallarta 2602, CP44130, Mexico

[13 ]Department of Oral Biology, University of Florida, Gainesville, FL 32610-0221, USA

[14 ]División de Medicina Interna, Servicio de Reumatología, Hospital Civil Dr. Juan I. Menchaca, Guadalajara, Jalisco, Salvador Quevedo y Zubieta S/N, CP 44240, Mexico

Article

Publisher ID: ar4207

DOI: 10.1186/ar4207

PMC ID: 4060281

PubMed ID: 23557279

SO-VID: 16d3f1c5-7d78-47dc-95ae-d1a07edc50d7

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 29 November 2012

Date revision received : 4 February 2013

Date accepted : 19 March 2013

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Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara

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Abstract

Introduction

Methods

Results

Conclusions

Related collections

Orthopedics

Most cited references 24

The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.

A novel autoantibody to a 155-kd protein is associated with dermatomyositis.

A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.

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Cited by 21

Most referenced authors 338