Objective To identify novel autoantibodies specific for dermatomyositis (DM), especially those specific for clinically amyopathic DM (C‐ADM). Methods Autoantibodies were analyzed by immunoprecipitation in 298 serum samples from patients with various connective tissue diseases (CTDs) or idiopathic pulmonary fibrosis (IPF). Antigen specificity of the sera was further examined by immunoblotting and indirect immunofluorescence (IF). The disease specificity and clinical features associated with the antibody of interest were determined. Results Eight sera recognized a polypeptide of ∼140 kd (CADM‐140 autoantigen) by immunoprecipitation and immunoblotting. Immunoreactivity was detected in the cytoplasm, and indirect IF revealed a granular or reticular pattern. Anti–CADM‐140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other CTDs or IPF. Interestingly, all 8 patients with anti–CADM‐140 antibodies had C‐ADM. Among 42 patients with DM, those with anti–CADM‐140 autoantibodies had significantly more rapidly progressive interstitial lung disease (ILD) when compared with patients without anti–CADM‐140 autoantibodies (50% versus 6%; P = 0.008). Conclusion These results indicate that the presence of anti–CADM‐140 autoantibodies may be a novel marker for C‐ADM. Further attention should be directed to the detection of rapidly progressive ILD in those patients with anti–CADM‐140 autoantibodies.

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.

Circulating CD14+ monocytes are precursors of phagocytes, such as macrophages and dendritic cells. Here we report primitive cells with a fibroblast-like morphology derived from human peripheral blood CD14+ monocytes that can differentiate into several distinct mesenchymal cell lineages. We named this cell population monocyte-derived mesenchymal progenitor (MOMP). MOMPs were obtained in vitro from human peripheral blood mononuclear cells cultured on fibronectin in the presence of fetal bovine serum alone as a source of growth factors. MOMPs had a unique molecular phenotype-CD14+CD45+CD34+type I collagen+-and showed mixed morphologic and molecular features of monocytes and endothelial and mesenchymal cells. MOMPs were found to be derived from a subset of circulating CD14+ monocytes, and their differentiation required that they bind fibronectin and be exposed to one or more soluble factors derived from peripheral blood CD14- cells. MOMPs could be expanded in culture without losing their original phenotype for up to five passages. The induction of MOMPs to differentiate along multiple limb-bud mesodermal lineages resulted in the expression of genes and proteins specific for osteoblasts, skeletal myoblasts, chondrocytes, and adipocytes. Our findings represent the first evidence that human circulating CD14+ monocytes are a source of progenitors that exhibit mesenchymal cell differentiation.

ObjectiveTo identify similarities and differences in the clinical features of adult Japanese patients with individual anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs).MethodsThis was a retrospective analysis of 166 adult Japanese patients with anti-ARS Abs detected by immunoprecipitation assays. These patients had visited Kanazawa University Hospital or collaborating medical centers from 2003 to 2009.ResultsAnti-ARS Ab specificity included anti-Jo-1 (36%), anti-EJ (23%), anti-PL-7 (18%), anti-PL-12 (11%), anti-KS (8%), and anti-OJ (5%). These anti-ARS Abs were mutually exclusive, except for one serum Ab that had both anti-PL-7 and PL-12 reactivity. Myositis was closely associated with anti-Jo-1, anti-EJ, and anti-PL-7, while interstitial lung disease (ILD) was correlated with all 6 anti-ARS Abs. Dermatomyositis (DM)-specific skin manifestations (heliotrope rash and Gottron’s sign) were frequently observed in patients with anti-Jo-1, anti-EJ, anti-PL-7, and anti-PL-12. Therefore, most clinical diagnoses were polymyositis or DM for anti-Jo-1, anti-EJ, and anti-PL-7; clinically amyopathic DM or ILD for anti-PL-12; and ILD for anti-KS and anti-OJ. Patients with anti-Jo-1, anti-EJ, and anti-PL-7 developed myositis later if they had ILD alone at the time of disease onset, and most patients with anti-ARS Abs eventually developed ILD if they did not have ILD at disease onset.ConclusionPatients with anti-ARS Abs are relatively homogeneous. However, the distribution and timing of myositis, ILD, and rashes differ among patients with individual anti-ARS Abs. Thus, identification of individual anti-ARS Abs is beneficial to define this rather homogeneous subset and to predict clinical outcomes within the “anti-synthetase syndrome.”

Objective. To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA). Methods. We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971—1990. Eight SSc–related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA. Results. Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti—U1 RNP, 66% in those with anti—DNA topoisomerase I (anti—topo I), and 30% in those with anti‐RNA polymerases I, II, and III (anti‐RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti—U1 RNP, pulmonary interstitial fibrosis in those with anti—topo I, and cardiac and renal involvement in those with anti‐RNAP. Conclusion. Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long‐term outcome.

To clarify the association of clinical and prognostic features with dermatomyositis (DM)specific autoantibodies (Abs) in adult Japanese patients with DM.

The modified Rodnan skin score (mRSS) is a measure of skin thickness and is used as a primary or secondary outcome measure in clinical trials of systemic sclerosis (scleroderma). This state-of-art review provides a historical perspective of the development of the mRSS, summarizes the performance of mRSS as an outcome measure, provides guidance on assessing mRSS, and makes recommendations for incorporation of the mRSS into clinical trials.

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