Anti-aminoacyl tRNA Synthetase Research Articles

Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) is a distinctive subtype of DM that carries a significant risk of interstitial lung disease (ILD). The mechanisms remain elusive. To explore the role of the type I interferon (IFN) system in the pathogenesis of anti-MDA5 DM. Twenty patients with anti-MDA5 DM were studied and compared with patients with anti-aminoacyl-tRNA synthetase (ARS) DM (n = 10) and autoantibody-negative patients with DM (n = 20). The levels of inflammatory cytokines, B-cell-activating factor (BAFF) and Krebs von den Lungen (KL)-6 in blood were tested by enzyme-linked immunosorbent assay and multiplex assays. Expressions of transcripts for IFN-associated sensors and type I IFN-inducible genes in peripheral blood mononuclear cells (PBMCs) were detected by real-time polymerase chain reaction. Expressions of the signal transducer and activator of transcription (STAT)1, interferon-stimulated gene (ISG)15 and MxA proteins in skin lesions were analysed by immunohistochemistry. Plasma IFN-α levels were significantly increased in patients with anti-MDA5 DM. PBMCs from patients with anti-MDA5 DM showed significant upregulation of the TLR3, TLR7, IFIH1 and DDX58 genes, as well as serial IFN-inducible genes. Skin biopsies from patients with anti-MDA5 DM were characterized by strong expression of the STAT1, ISG15 and MxA proteins. In the patients with anti-MDA5 DM and ILD with high IFN-α production, there was a positive quantitative correlation between IFN-α and BAFF (rs = 0·63, P = 0·044). In addition, the higher levels of BAFF paralleled the higher concentrations of KL-6 (rs = 0·86, P = 0·0012). Our data confirm the aberrant activation of the type I IFN system in anti-MDA5 DM. Overproduction of IFN-α linked with BAFF may be implicated in the development of ILD.

Potential of Krebs von den Lungen-6 as a predictor of relapse in interstitial pneumonia with anti-aminoacyl tRNA synthetase antibodies-positive dermatomyositis.

To identify a predictor of relapse in interstitial pneumonia (IP) in patients with anti-aminoacyl tRNA synthetase antibodies-positive dermatomyositis (ARS-DMIP). This retrospective cohort study comprised 27 ARS-DMIP patients. We compared clinical and laboratory findings between the relapse and non-relapse groups during 2 years after treatment initiation to find predictors of relapse in IP. Candidate predictors were further assessed by analysing the relationship with the relapse of IP. One patient with ARS-DMIP died. About 7 (26.9%) of the remaining 26 patients with ARS-DMIP had a relapse of IP. We found that the levels of serum Krebs von den Lungen-6 (KL-6) in the relapse group were significantly higher than those in the non-relapse group at the time points before treatment (P = .046) and after treatments, including 6 (P = .004), 12 (P = .013), 18 (P = .003) and 24 months (P < .001). The KL-6 values that maximised the area under the ROC curve were 2347 U/mL before treatment, 622 U/mL after 6 months and 468 U/mL after 12 months. The relapse rates after 104 weeks were significantly higher in patients with KL-6 levels ≥2400 U/mL before treatment (P = .014), ≥600 ng/mL after 6 months (P < .005) and ≥470 U/mL after 12 months (P = .010). These findings suggest that the levels of KL-6 before and after treatment in ARS-DMIP may represent the disease activity of IP, and they may be useful as the predictor of relapse in IP in patients with ARS-DMIP.

Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis.

Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

Idiopathic Inflammatory Myopathy and Anti-aminoacyl-tRNA Synthetase Antibody

Anti-aminoacyl-tRNA synthetase (ARS) antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-KS, anti-OJ, anti-Ha, and anti-Zo antibodies) are found in 25 to 40% of myositis patients. The patients with these antibodies have anti-synthetase syndrome with one or more of the following clinical features: myositis, interstitial lung disease, arthritis, fever, Raynaud's phenomenon, and mechanic's hands. In Japan, health insurance coverage of treatments for patients in whom the "anti-ARS antibodies," anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, and anti-KS are detected by enzyme-linked immunosorbent assay was approved by the Ministry of Health, Labour and Welfare in 2014. Recently, clinical features have been discovered to be heterogeneous. Patients with the anti-PL-7, anti-PL-12, anti-KS, and anti-OJ antibodies exhibit interstitial lung disease rather than myositis. Interstitial lung disease is related to the prognosis of this syndrome. Regarding histopathological findings of the muscle, perimysial connective tissue fragmentation with positive staining for alkaline phosphatase is the characteristic feature. Myonuclear actin filament inclusions are also detected. A recent work demonstrated that immunization of mice with histidyl-tRNA synthetase results in muscle inflammation consistent with myositis. These findings promote understanding of the pathological mechanism of the development of myositis associated with anti-ARS antibodies.

Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients.

To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

Elevated \u03b1-defensin levels in plasma and bronchoalveolar lavage fluid from patients with myositis-associated interstitial lung disease

BackgroundInterstitial lung disease (ILD) is a prognostic indicator of poor outcome in myositis. Although the pathogenesis of myositis-associated ILD is not well understood, neutrophils are thought to play a pivotal role. Neutrophils store azurophil granules that contain defensins, which are antimicrobial peptides that regulate the inflammatory response. Here, we evaluated levels of the human neutrophil peptides (HNPs) α-defensin 1 through 3 in patients with myositis-associated ILD to determine whether HNPs represent disease markers and play a role in the pathogenesis of myositis-associated ILD.MethodsHNP levels were measured in the plasma and bronchoalveolar lavage fluid (BALF) of 56 patients with myositis-associated ILD and 24 healthy controls by enzyme-linked immunosorbent assay.ResultsAnalysis revealed significantly higher HNP levels in plasma and BALF samples from patients with myositis-associated ILD as compared to those of healthy controls; however, plasma HNPs were significantly correlated with total cell counts in BALF. Additionally, BALF HNP levels were positively correlated with serum surfactant protein-A and the percentage of neutrophils in BALF, and BALF HNP levels correlated with the percentage of reticular opacities in high-resolution computed tomography results for patients with anti-aminoacyl-tRNA synthetase (ARS) antibody positive myositis-associated ILD. Survival did not differ between patients with higher and lower levels of plasma and BALF HNPs.ConclusionsPlasma and BALF HNPs might reflect the disease activities of myositis-associated ILD, especially in patients with anti-ARS antibody positive myositis-associated ILD. However further studies are necessary to clarify whether HNPs represent disease markers and play roles in disease pathogenesis.

Anti-aminoacyl tRNA synthetase antibody-positive clinically amyopathic dermatomyositis.

Anti-aminoacyl tRNA synthetase antibody-positive clinically amyopathic dermatomyositis.

Clinical characteristics of dermatomyosits/polymyositis associated interstitial lung disease according to the autoantibody.

Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. We identified 52 patients, of whom 30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p < 0.001), and LDH (r=0.910, p < 0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p < 0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p < 0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p < 0.001). ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort. J. Med. Invest. 65:251-257, August, 2018.

Anti-Aminoacyl tRNA Synthetases Antibodies in Japanese Patients with Interstitial Lung Disease

Objectives: In the present study, we have sought to establish the clinical and immunological characteristics of Japanese patients with interstitial lung disease (ILD). Methods: Serum samples from 35 patients of ILD were screened for autoantibodies using RNA and protein immunoprecipitation assays. Patients with or without serum antibodies to aminoacyl tRNA synthetases (ARS) were assessed clinically and compared. Results: Sera from 12 of 35 (34%) patients with ILD (mean age at onset = 49.7 yrs; range 27 - 65 yrs) were found to contain anti-ARS antibodies (anti-EJ: 3 patients; anti-OJ: 2 patients; anti-PL-12: 3 patients; anti-KS: 4 patients). Nine of the 12 (75%) were female. Six (50%) had Raynaud’s phenomenon, 5 (42%) had arthralgia/arthritis and four (33%) had rheumatoid factor. Lung biopsy specimens of 8 patients with anti-ARS antibodies were examined histologically in detail. The following was determined: Two patients had usual interstitial pneumonia; 3 had non-specific interstitial pneumonia; one had organizing pneumonia; one had lymphocyte interstitial pneumonia and the remaining patient had desquamative interstitial pneumonia. Age at disease onset was significantly lower and the frequency of Raynaud’s phenomenon was significantly greater in these patients compared to anti-ARS-negative patients (49.7 yrs vs. 62.6 yrs, p = 0.004; 50% vs. 4%, p = 0.003, respectively). Conclusions: These results indicate that the presence of anti-ARS autoantibodies correlates with ILD without definite diagnosis of connective tissue diseases as well as polymyositis/dermatomyositis (PM/DM) with ILD in Japanese patients.

019 Distinct clinicopathologic and radiological manifestations of the skin, lung, and muscle diseases in patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase antibodies

019 Distinct clinicopathologic and radiological manifestations of the skin, lung, and muscle diseases in patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase antibodies

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies

BackgroundThe aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type. MethodsA total of 182 patients with PM/DM-ILD were observed retrospectively. Antiaminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene5 (MDA5) antibodies were screened using immunoblotting approach. The patients with ILD were divided into 3 groups: MDA5 (with anti-MDA5 antibody), ARS (with anti-ARS antibody) and MSN (without anti-MDA5 or anti-ARS antibody) group. Pulmonary features, treatment responses and prognoses were compared among the groups. ResultsA higher percentage of rapidly progressive ILD (RP-ILD) occurrences (55.8% versus 25% versus 16.9%, P < 0.001) was observed in the MDA5 group compared to ARS and MSN groups. The MSN group experienced lower dyspnea (48.2% versus 79% versus 71.4%, P = 0.001) and fever (18.1% versus 39.5% versus 37.5%, P = 0.01) frequencies compared to MDA5 and ARS groups. Response to 6-month treatment among 95 patients showed highest deterioration ratio (70%, P = 0.001) of ILD in the MDA5 group. Additionally, the highest frequency of ILD improvement (60%, P = 0.04) was observed in the ARS group. During the observation period, 24 patients died of respiratory failure. The 5-year survival rates were significantly lower in MDA5 group (50.2%) compared to ARS group (97.7%) or the MSN group (91.4%) (P < 0.001). ConclusionsMDA5-ILD was associated with severe pulmonary manifestations, poor response to treatment and aggravated prognosis. The ARS-ILD group had favorable treatment response and prognosis. MSN-ILD patients had relatively worse treatment response and prognosis compared to the ARS group, even though they expressed milder pulmonary manifestation.

Interstitial lung disease-associated antisynthetase syndrome

Interstitial lung disease (ILD) is one of the major extramuscular manifestations of polymyositis (PM) and dermatomyositis (DM). Presentation of PM and DM with ILD is not uncommon, but its clinical and radiological features can be similar to other conditions and can be challenging to diagnose. The presence of anti-aminoacyl tRNA synthetase antibodies in the presence of ILD is diagnostic of antisynthetase syndrome. A delayed diagnosis can be associated with the progression of pulmonary involvement and potentially increased morbidity. Timely diagnosis leads to appropriable lifesaving treatment. We report on a patient with chronic respiratory symptoms who had positive anti-Jo-1 antibodies and presented in respiratory failure, requiring non-invasive ventilation.

Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease

ObjectivesMyositis-specific autoantibodies (MSAs) are associated with clinical phenotypes in polymyositis/dermatomyositis (PM/DM). No study has investigated the clinical features based on comprehensive MSA assessment in PM/DM-associated interstitial lung disease (ILD). We aimed to determine the practical significance of MSAs in PM/DM-ILD. MethodsSixty consecutive PM/DM-ILD patients were retrospectively analysed. Serum MSAs were comprehensively measured using immunoprecipitation assay. Clinical features and prognosis were compared among MSA subgroups. ResultsTwenty-six (43.3%) PM/DM-ILD patients were anti-aminoacyl tRNA-synthetase antibody-positive (anti-ARS-positive), 15 (25.0%) were anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5-positive), 3 (5%) were anti-signal recognition particle antibody-positive, 1 (1.7%) was anti-transcriptional intermediary factor 1-gamma antibody-positive, and 15 (25%) were MSA-negative. There were significant differences in clinical features, including ILD form, serum ferritin and surfactant protein-D levels at ILD diagnosis, and high-resolution CT pattern among the anti-ARS-positive, anti-MDA5-positive and MSA-negative groups. The anti-MDA5-positive group showed the lowest 90-day survival rate (66.7%, anti-MDA5-positive; 100%, anti-ARS-positive; 100%, MSA-negative; P < 0.01). The anti-ARS-positive group had the highest 5-year survival rate (96%, anti-ARS-positive; 66.7%, anti-MDA5-positive; 68.3%, MSA-negative, P = 0.02). Univariate analysis revealed that anti-ARS antibody was associated with better prognosis (HR = 0.45; 95% CI, 0.18–0.89; P = 0.02), whereas anti-MDA5 antibody was associated with poorer prognosis (HR = 1.90; 95% CI, 1.02–3.39; P = 0.04). ConclusionsThe comprehensive MSA assessment demonstrated that anti-ARS and anti-MDA5 antibodies were two major MSAs, and the clinical features differed depending on MSA status in PM/DM-ILD. Assessment of anti-ARS and anti-MDA5 antibodies is practically useful for predicting clinical course and prognosis in PM/DM-ILD patients.

Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1

Sir, The papers by Mescam-Mancini et al. (2015) and Stenzel et al. (2015) are of particular interest, at least partially addressing the important question whether anti-synthetase syndrome is pathologically distinct from other idiopathic inflammatory myopathies. Mescam-Mancini et al. (2015) beautifully demonstrated that patients with anti-Jo-1 antibodies, one of the anti-aminoacyl-tRNA synthetase (ARS) antibodies, characteristically show perifascicular necrosis on muscle pathology. However, they did not deal with anti-synthetase syndrome patients with anti-ARS antibodies other than anti-Jo-1, raising a question whether perifascicular necrosis is characteristic only of myopathies associated with anti-Jo-1 antibodies or is observed also in those associated with other anti-ARS antibodies. We have analysed muscle samples from patients with anti-Jo-1 antibodies ( n …

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease.

Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are closely associated with interstitial lung disease in polymyositis and dermatomyositis. Anti-ARS-positive patients develop common clinical characteristics termed anti-synthetase syndrome and share a common clinical course, in which they respond well to initial treatment with glucocorticoids but in which disease tends to recur when glucocorticoids are tapered. Anti-MDA5 antibody is associated with rapidly progressive interstitial lung disease and poor prognosis, particularly in Asia. Therefore, intensive immunosuppressive therapy is required for anti-MDA5-positive patients from the early phase of the disease. New enzyme-linked immunosorbent assays to detect anti-ARS and anti-MDA5 antibodies have recently been established and are suggested to be efficient and useful. These assays are expected to be widely applied in daily practice.

Antisynthetase syndrome: An under-recognized cause of interstitial lung disease.

Background:Antisynthetase syndrome (AS) is an uncommon and under-recognised connective tissue disease characterized by the presence of antibodies to anti-aminoacyl t-RNA synthetase along with features of interstitial lung disease (ILD), myositis and arthritis. The aim of the current study is to describe our experience with management of AS.Materials and Methods:This was a 2-year (2013-2014) retrospective analysis of patients diagnosed with anti-Jo-1-related AS. The presence of anti-Jo-1 antibody was tested by the immunoblot assay. All patients underwent high-resolution computed tomography of the chest, transthoracic echocardiography and evaluation for inflammatory myositis. Transbronchial lung biopsies and muscle biopsies were obtained when clinically indicated.Results:Nine patients (mean age: 43.8 years) were diagnosed with anti-Jo-1-related AS. The median duration of symptoms before diagnosis of AS was 6 months. All patients were negative for antinuclear antibodies by indirect immunofluorescence. The prevalence of ILD, myositis and arthritis at presentation was 100%, 77.8% and 55.6%, respectively. The most common ILD pattern was non-specific interstitial pneumonia (n = 6) followed by organizing pneumonia (n = 2) and usual interstitial pneumonia (n = 1). ILD was the sole manifestation in two patients and was subclinical in two patients. Six patients had pleuropericardial effusions, three patients had pulmonary artery hypertension and two patients had venous thromboembolism. Eight of the nine patients improved after treatment with steroids and other immunosuppressants.Conclusion:Antisynthetase syndrome is an important and a treatable cause of ILD. Strong clinical suspicion is needed to achieve an early diagnosis.

Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study.

BackgroundIn polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established.ObjectiveWe aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients.MethodsForty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group).ResultsAnti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01).ConclusionsThe presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD.

Recent Treatment of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies.

Interstitial lung disease (ILD) is a prognostic factor for poor outcome in polymyositis (PM)/dermatomyositis (DM). The appropriate management of ILD is very important to improve the prognosis of patients with PM/DM. ILD activity and severity depend on the disease subtype. Therefore, clinicians should determine therapeutic strategies according to the disease subtype in each patient with PM/DM. Anti–melanoma differentiation-associated gene 5 antibody and hyperferritinemia predict the development and severity of rapidly progressive (RP) ILD, particularly in East Asian patients. Combination therapy with corticosteroids, intravenous cyclophosphamide pulse, and calcineurin inhibitors should be administered in RP-ILD. In contrast, patients with anti–aminoacyl-tRNA synthetase (ARS) show better responses to corticosteroids alone. However, ILDs with anti-ARS often display disease recurrence or become refractory to corticosteroid monotherapy. Recent studies have demonstrated that the administration of tacrolimus or rituximab in addition to corticosteroids may be considered in ILD patients with anti-ARS. Large-scale, multicenter randomized clinical trials should be conducted in the future to confirm that the aforementioned agents exhibit efficacy in ILD patients with PM/DM. The pathophysiology of ILD with PM/DM should also be elucidated in greater detail to develop effective therapeutic strategies for patients with ILD in PM/DM.

Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients.

The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis. First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD. In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (s.d. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (s.d. 53) and 21 months (s.d. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (s.d. 10) and 31 months (s.d. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (s.d. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies. ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP.

Distinct arthropathies of the hands in patients with anti-aminoacyl tRNA synthetase antibodies: usefulness of autoantibody profiles in classifying patients

The aim of this study was to characterize arthropathies of the hands associated with antiaminoacyl tRNA synthetase (ARS) autoantibodies. Fifty-six patients with anti-ARS antibodies were selected from consecutive patients who visited Keio University Hospital between1983 and 2011, based on their joint symptoms and the availability of hand X-rays. Their clinical characteristics, anti-CCP antibodies, RF, and hand X-ray findings were retrospectively examined. Based on characteristic hand X-ray findings, the anti-ARS-positive patients with joint symptoms could largely be categorized into three groups. The predominant group (64%) was patients with no significant X-ray findings. The remaining patients with destructive changes were classified into two distinct groups. One group had mainly erosions in the PIP and MCP joints and/or ankylosis of the wrists with anti-CCP and RF, which is consistent with the features of RA. The other group showed subluxation of the thumbs and periarticular calcification that was independent of anti-CCP or RF, which is exclusively found in anti-Jo-1-positive patients. Autoantibody profiles, including anti-CCP, RF and individual anti-ARS specificities, are useful in classifying anti-ARS-associated arthropathies of the hands into RA or anti-Jo-1-related disorders.