The association between Mi‐2 antibodies and dermatomyositis

Targoff, Ira N.; Reichlin, Morris

doi:10.1002/art.1780280711

Cited by 240 publications

(144 citation statements)

References 18 publications

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“…Serum was stored at -20°C. The results of testing of some of these sera for antibodies to Jo-1 (l-3,6), Mi-2 (1,3,4), and other serologic parameters (1) have been previously reported. Serum from 1 patient (LT) who was seen in Baltimore was previously determined to have anti-PL-7 (by immunoprecipitation of tRNAth' [5]); this serum was used as a positive control and was analyzed further.…”

Section: Methodsmentioning

confidence: 90%

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Antibody to threonyl–transfer rna synthetase in myositis sera

Targoff

Arnett

Reichlin

1988

Arthritis & Rheumatism

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The prevalence and clinical correlations of antithreonyl-transfer RNA synthetase (anti-PL-7), as well as the relationship of anti-PL-7 to anti-histidyl-transfer RNA synthetase (anti-Jo-1) were studied in 109 sera from patients with myositis. Inhibition of threonine aminoacylation was used to screen for anti-PL-7. Sera from 3 patients, 2 with polymyositis and 1 with polymyositisoverlap syndrome, and a fourth serum from a patient with dermatomyositis, which was previously found to contain anti-PL-7, inhibited >90% of activity (3.7% of 109 sera). All 4 sera reacted strongly in an enzyme-linked immunosorbent assay with enzyme that was either affinity purified with anti-PL-7 or was biochemically purified. There was no indication of crossreactivity by aminoacylation inhibition or, for most sera, by enzyme-linked immunosorbent assay. Anti-PL- 7 is an uncommon myositis-associated antibody that is independent of anti-Jo-1, but is directed at a functionally related enzyme.Polymyositis (PM) and dermatomyositis (DM) are associated with a high frequency of antinuclear and anticytoplasmic autoantibodies (1). Some of them, including anti-Jo-1 (2), anti-PM-Scl(3), and anti-Mi-2 (4), are found almost exclusively in serum from patients with myositis. The myositis-associated antibodies are distinguished by the great variety of specificities and by the relatively frequent association of their antigens with transfer RNA (tRNA) (5). Anti-Jo-1, the antibody most commonly found in myositis patients, is present in only 20% of all myositis patients (2) and in about 35% of its characteristic subgroup, adult PM (6). This antibody reacts with histidyl-tRNA (his-tRNA) synthetase (7), the enzyme that catalyzes the attachment of histidine to its cognate tRNA (aminoacylation of tRNAhis). Autoantibodies to 2 of the other aminoacyl-tRNA synthetases, threonyl-tRNA (thr-tRNA) synthetase (anti-PL-7) (5,8) and alanyl-tRNA synthetase (anti-PL-12) (9), have also been described, and their presence has been associated with myositis. Other antibodies directed at antigens associated with tRNA have been found in myositis sera, as demonstrated by the ability of these sera to immunoprecipitate tRNA (5,10,11), but the antigens have not been identified. Although antibodies to thr-tRNA synthetase and alanyl-tRNA synthetase and other tRNArelated proteins are uncommon, the association of the group as a whole with myositis seems to be important.Bernstein et a1 (lo), using immunoprecipitation with labeled HeLa cell extracts to detect the antibody, reported the presence of anti-PL-7 in the sera of 3% of

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Section: Methodsmentioning

confidence: 90%

“…Optimum coating dilution was determined by coating wells with serial dilutions of the eluate (in PBS), and developing with 1 : 1,000 diluted VP serum (anti-PL-7); for PL-7,0.5-1 pg/ml was generally used for coating. Otherwise, indirect ELISA and antigen-inhibition ELISA were performed as described previously for other antigens (4,6).…”

Section: Methodsmentioning

confidence: 99%

Antibody to threonyl–transfer rna synthetase in myositis sera

Targoff

Arnett

Reichlin

1988

Arthritis & Rheumatism

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“…anti-Zo (phenylalanyl-tRNA synthetase) and anti-Ha (tyrosyl-tRNA synthetase) [38].In DM antibodies to Mi-2, which is a component of the nucleosome remodelling deacetylase complex, has a high specificity, particularly for the adult form of the disease [39,40].More recently, a number of newer autoantibodies associated with particular subgroups of DM cases have been characterised including anti-TIF-1α/γ, anti-MDA5 and anti-NXP-2 and these have been reviewed elsewhere [31].…”

Section: Myositis Specific Autoantibodiesmentioning

confidence: 99%

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

Moran

Mastaglia

2014

Neuromuscular Disorders

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The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications. Neuromuscular Disorders, 24 (11) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Originally identified as an autoantigen in dermatomyositis (DM), 2 the Mi-2 ATPase is now known to be the core subunit of the nucleosome remodeling deacetylase (NuRD) complex (1)(2)(3)(4)(5). Two isoforms of Mi-2 exist (␣ and ␤, also CHD3 and CHD4) and appear to have similar biological function.…”

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confidence: 99%

UV Radiation Regulates Mi-2 through Protein Translation and Stability

Burd

Kinyamu

Miller

et al. 2008

Journal of Biological Chemistry

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Dermatomyositis (DM) is an autoimmune disease, which is often accompanied by the development of disease-specific autoantibodies directed against the SNF2-superfamily helicase, Mi-2. Recent evidence suggests that ultraviolet radiation exposure may be an important risk factor for the development of not only the disease but also specific autoimmunity against Mi-2. Consequently, we investigated the effects of ultraviolet radiation on Mi-2 protein expression. We observed an increase in protein levels upon ultraviolet radiation exposure in cell culture systems. These changes in expression occur quite rapidly, are maximized just 1 h following exposure, and are unique to Mi-2 when compared with other members of the NuRD complex. Changes in protein levels are not mediated through transcriptional mechanisms. Treatment results in a more efficiently translated message through regulatory elements in the 5-UTR region of the transcript. Investigation into protein half-life further demonstrated increased stability of Mi-2 following UV exposure. Taken together, we describe a system by which Mi-2 protein expression can be quickly increased following UV exposure and then maintained up to 16 h later. These data provide a novel regulation of an important transcriptional regulator and provide insight into the possible mechanisms of the development of DM and associated autoantibodies.

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The association between Mi‐2 antibodies and dermatomyositis

Cited by 240 publications

References 18 publications

Antibody to threonyl–transfer rna synthetase in myositis sera

Antibody to threonyl–transfer rna synthetase in myositis sera

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

UV Radiation Regulates Mi-2 through Protein Translation and Stability

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