Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy

Kaji, Kenzo; Fujimoto, Manabu; Hasegawa, Minoru; Kondo, Miki; Saito, Yasuharu; Komura, Kazuhiro; Matsushita, T.; Orito, Hidemitsu; Hamaguchi, Yasuhito; Yanaba, Koichi; Itoh, Munenari; Asano, Yoshihide; Seishima, Mariko; Ogawa, Fumihide; Sato, Shinichi; Takehara, Kazuhiko

doi:10.1093/rheumatology/kel161

Cited by 281 publications

(236 citation statements)

References 16 publications

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“…A variety of serum autoantibodies are specifically detected in patients with PM/DM, including antibodies reactive with aminoacyl-transfer RNA synthetase (aaRS) (5), signal recognition particle (SRP) (6), Mi-2 (7), and p155 (8,9). These autoantibodies are associated with distinct clinical subsets of PM/DM.…”

mentioning

confidence: 99%

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Sato¹,

Hoshino²,

Satoh³

et al. 2009

Arthritis & Rheumatism

540

422

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ObjectiveTo identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C‐ADM) and rapidly progressive interstitial lung disease (ILD).MethodsAn anti–CADM‐140 antibody–positive prototype serum sample was used to screen a HeLa cell–derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro–transcribed and in vitro–translated products using anti–CADM‐140 antibody–positive and anti‐CADM‐140 antibody–negative sera. The lysates of COS‐7 cells transfected with the putative antigen were similarly tested. An enzyme‐linked immunosorbent assay (ELISA) to detect the anti–CADM‐140 antibody was established using a recombinant CADM‐140 antigen, and its specificity and sensitivity for C‐ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases.ResultsBy cDNA library screening and immunoprecipitation of in vitro–transcribed and in vitro–translated products, we obtained a cDNA clone encoding melanoma differentiation–associated gene 5 (MDA‐5). The anti–CADM‐140 antibodies in patients' sera specifically reacted with MDA‐5 protein expressed in cells transfected with full‐length MDA‐5 cDNA, confirming the identity of MDA‐5 as the CADM‐140 autoantigen. The ELISA, using recombinant MDA‐5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the “gold standard” immunoprecipitation assay, and was useful for identifying patients with C‐ADM and/or rapidly progressive ILD.ConclusionGiven that RNA helicase encoded by MDA‐5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C‐ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA‐5 protein makes detection of the anti–CADM‐140 antibody routinely available.

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mentioning

confidence: 99%

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Sato¹,

Hoshino²,

Satoh³

et al. 2009

Arthritis & Rheumatism

540

422

View full text Add to dashboard Cite

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“…It was described first by Targoff et al (Targoff et al, 2006b). The clinical manifestations of this reactivity involve high prevalences in dermatomyositis, as reported by Targoff et al, but with a high specificity the occurrence of this MSA correlates with a risk of malignancies as (Kaji et al, 2007). This observation was statistically underlined when Selva O´Canaghan et al performed a meta analysis for anti TIF 1 gamma antibodies and predictive values for malignancies (Selva-O'Callaghan et al, 2010) and found that anti p155/TIF1 y antibodies have a 70 % sensitivity and a 90 % specificity to detect occult malignancies in DM.…”

Section: Tif1 Gammamentioning

confidence: 67%

Serological Aspects of Myositis

Schulte-Pelkum¹

2011

Idiopathic Inflammatory Myopathies - Recent Developments

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“…It was demonstrated that antigenic myositis-specific autoantigens are expressed in both tumor cells and myoblasts, and then myositis-specific autoantigen is expressed in an initial tumor leading to the generation of both specific T and B cells targeting those antigens, and subsequently stimulate immune responses previously generated in the anti-tumor response. [12][13][14][15] These may explain the mechanism of the coexistence of DM and cancer.…”

Section: Discussionmentioning

confidence: 99%

“…16 Thus, the determination of clinical and laboratory signs for association with malignancy are of great importance for the disease prognosis. In some studies, relatively high proportions of anti-155/140 antibodies were detected in cancer-associated DM patients, and these have an excellent positive predictive value 12,13,17 Therefore, introduction of a commercial kit for this antibody to be applied in clinical screening may be beneficial. It was also shown that anti-Jo-1 antibody and cancer-associated DM, or interstitial lung disease and cancerassociated DM appear mutually exclusive.…”

Section: Discussionmentioning

confidence: 99%

Metachronous Basal Cell Carcinoma and Primary Plasmacytic Leukemia Associated With Dermatomyositis

2014

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Dermatomyositis (DM) is an autoimmune inflammatory disease characterized by the association of progressive proximal muscle weakness and specific cutaneous signs, as well as multisystemic manifestations.1 Although the association between DM and elevated risks of comorbid cancers has been studied extensively, 2 individuals with multiple malignancies associated with DM are rare. Some previous reports associated DM and two different types of malignancies in the same individual. [3][4][5] To the best of our knowledge, this is the first case of the metachronous basal-cell carcinoma of the nasolabial fold and plasma cell leukemia occurring in the same DM patient over a period of time. CASE REPORTA 71-year-old female patient presented with a four-month history of muscle weakness, such as difficulty in raising her hands over the level of her shoulders and walking up and down the stairs. Physical examination revealed periorbital violaceous erythema and Gottron's papules on both elbows. Strength testing demonstrated a grade of 3/5 for the cervical muscle, upper and lower limbs. Laboratory tests showed elevated muscle enzymes with a creatine phosphokinase

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Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy

Abstract: This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

Cited by 281 publications

References 16 publications

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Serological Aspects of Myositis

Metachronous Basal Cell Carcinoma and Primary Plasmacytic Leukemia Associated With Dermatomyositis

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