Synthetase Antibodies Research Articles

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.

ABNORMAL NAILFOLD VIDEOCAPILLAROSCOPY IN PATIENTS WITH ANTISYNTHETASE SYNDROME: CASE REPORTS AND REVIEW OF THE LITERATURE

Classified as a distinct subset of idiopathic inflammatory myopathies, anti-synthetase syndrome is an orphan autoimmune disease characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies associated with a spectrum of clinical features including interstitial lung disease, myositis or dermatomyositis, chronic polyarthritis, fever, mechanic‘s hands and Raynaud‘s phenomenon. The main objective of our study was to evaluate nailfold capillary abnormalities in a series of cases diagnosed with anti-synthetase syndrome, aiming to describe capillaroscopy findings and to identify potential relation with clinical and functional outcomes. Irrespective of clinical and serological disease subtype, significant capillaroscopic changes may help diagnosis and identify negative prognostic factors, advancing the role of routine capillaroscopy in the decisional algorithm of anti-synthetase syndrome. Nailfold videocapillaroscopy is able to provide valuable information in patients with anti-tRNA synthetase myositis, suggesting that diffuse microangiopathy represents an early pathobiologic event.

COULD ANTI-SYNTHETASE SYNDROME BE A GOOD PREDICTOR FACTOR FOR INTERSTITIAL LUNG DISEASE?

Anti-synthetase syndrome (SAS) is an autoimmune inflammatory myopathy, whose immune profile is dominated by anti-RNA synthetase antibodies (ARS), with a specific clinical phenotype. The major diagnostic criteria of SAS include the triad of myositis, arthritis and interstitial lung disease (ILD), on the background of positive anti-ARS antibodies. ILD in SAS, has a good evolution compared to the one in PM/DM, due to protective presence of anti Jo-1 antibodies.

Skeletal Muscle Involvement in Antisynthetase Syndrome

Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. However, antisynthetase syndrome is not included in the histological subsets of idiopathic inflammatory myopathies. To elucidate the clinical features of myositis in patients with antisynthetase syndrome. In this cohort study, muscle biopsy and blood samples were collected from 460 patients with idiopathic inflammatory myositis from various regional referral centers throughout Japan between October 2010 and December 2014. Data were analyzed in March 2016. Six different anti-ARS antibodies were detected in serum by RNA immunoprecipitation. Line blot assay and protein immunoprecipitation were also performed. HLA-DRB1 alleles were genotyped. The main outcomes were muscle manifestations and histological findings. Predisposing factors, extramuscular symptoms, and follow-up information were also studied. Of 460 patients with idiopathic inflammatory myopathies, 51 (11.1%) had anti-ARS antibodies. Of this subset, 31 (61%) were women, with a mean (SD) age at disease onset of 60.2 (16.1) years. Among 6 different anti-ARS antibodies, only 1-the anti-OJ antibody-was not detected by line blot assay but by RNA immunoprecipitation. There were no significant HLA-DRB1 alleles associated with anti-ARS antibodies. All 51 patients presented with muscle limb weakness; 14 (27%) had severe limb weakness, 17 (33%) had neck muscle weakness, 15 (29%) had dysphagia, and 15 (29%) had muscle atrophy. Although patients with anti-OJ antibodies showed severe muscle weakness, the clinical presentations of antisynthetase syndrome were relatively homogeneous. In histology, perifascicular necrosis, the characteristic finding of antisynthetase syndrome, was found in 24 patients (47%). Myositis with anti-ARS antibodies responded to the combination of immunosuppressive therapy with favorable outcomes. Interstitial lung disease, found in 41 patients (80%), was more closely associated with mortality than myositis. Although clinical presentations of antisynthetase syndrome were relatively homogeneous, anti-OJ antibodies were associated with severe muscle involvement. Antisynthetase syndrome is a clinical and histological subset among idiopathic inflammatory myopathies.

Integrated Diagnosis Project for Inflammatory Myopathies: An association between autoantibodies and muscle pathology.

Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of inflammatory myopathies has been based on clinical diagnoses, pathological diagnoses, and autoantibodies, independently. The clinical phenotypes of inflammatory myopathies are characterized by various autoantibodies that are originally detected by RNA or protein immunoprecipitation. However, since the correlation between histological features and autoantibodies had not been fully elucidated, we created the "Integrated Diagnosis Project for Inflammatory Myopathies" in October 2010. Based on our work and previous studies, the three major subsets of inflammatory myopathies defined by autoantibodies are immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome, and dermatomyositis. IMNM is the pathological entity, characterized by significant necrotic and regeneration muscle fibers with minimal or no inflammatory cell infiltration. The detection of autoantibodies against signal recognition particles or 3-hydroxy-3-methylglutaryl-coenzyme A reductase is important for the diagnosis of IMNM. Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is the clinical entity based on the presence of aminoacyl transfer RNA synthetase antibodies. Perifascicular necrosis is a distinctive hallmark of antisynthetase syndrome in muscle pathology. The diagnosis of dermatomyositis is usually based on clinical features of typical skin rash. Several autoantibodies are associated with specific subsets of dermatomyositis. Myxovirus resistance A expression in the myofiber cytoplasm has a better sensitivity for the diagnosis of dermatomyositis compared to perifascicular atrophy. The screening of autoantibodies has clinical relevance for managing patients with inflammatory myopathies.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies

RationaleAnti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. ObjectivesTo elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. MethodsA two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. Measurements and main resultsDuring the observational period (median 49 months; range, 1–114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. ConclusionsThe long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

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.

Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy.

BackgroundAnti-glycyl-tRNA synthetase (anti-EJ) antibody is occasionally positive in patients with interstitial lung disease (ILD). We aimed to define the clinical, radiological and pathological features of patients with anti-EJ antibody-positive ILD (EJ-ILD).MethodsWe retrospectively analyzed the medical records of 12 consecutive patients with EJ-ILD who underwent surgical lung biopsy.ResultsThe median follow-up time was 74 months (range, 17–115 months). The median age was 62 years (range, 47–75 years). Seven of 12 patients were female. Eight patients presented with acute onset. Six patients eventually developed polymyositis/dermatomyositis. On high-resolution computed tomography, consolidation and volume loss were predominantly observed in the middle or lower lung zone. Nine patients presented pathologically nonspecific interstitial pneumonia with organizing pneumonia, alveolar epithelial injury and prominent interstitial cellular infiltrations whereas the other three patients were diagnosed with unclassifiable interstitial pneumonia. Although all patients but one improved with the initial immunosuppressive therapy, five patients relapsed. When ILD relapsed, four of the five patients were treated with corticosteroid monotherapy. Four of the six patients without relapse have been continuously treated with combination therapy of corticosteroid and immunosuppressant.ConclusionsPatients with EJ-ILD often had acute onset of ILD with lower lung-predominant shadows and pathologically nonspecific interstitial pneumonia or unclassifiable interstitial pneumonia with acute inflammatory findings. Although the disease responded well to the initial treatment, relapse was frequent. Because of the diversity of the clinical courses, combination therapy of corticosteroid and immunosuppressant should be on the list of options to prevent relapse of EJ-ILD.

Topical 5-Fluorouracil is a Novel Targeted Therapy for the Keratocystic Odontogenic Tumor

The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis. An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy's solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014. Outcome variables included time to recurrence and peripheral nerve injury. KOT specimens in these patients were immunostained with p53, Ki-67, thymidylate synthetase (TS), thymidylate phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) antibodies. Semiquantitative staining scores were calculated for all immunohistochemistry sections examined. Descriptive statistics were computed using Fisher exact test and Kaplan-Meier analysis as appropriate with the P value set at .05. Thirty-two patients with 32 KOTs were reviewed (41% in women and 59% in men). There were no KOT recurrences in the 5-FU group (n= 11), whereas there were 4 recurrences in the MC group (n= 21; P= .190). There was a significantly lower incidence of inferior alveolar nerve paresthesia with 5-FU treatment (P= .039). Immunohistochemical staining showed upregulation of TP (P < .0001) and DPD (P<.0001) and no change in TS (P > .05) in inflamed KOTs. 5-FU effectively treats KOTs with less postoperative morbidity than conventional treatment with MC. Low TS and upregulated TP expressions in inflamed KOTs suggest increased 5-FU efficacy in inflamed KOTs. Topical 5-FU is a novel therapy for KOTs and provides a targeted molecular approach to treatment.

Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease.

We attempted to clarify whether the presence of anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) or anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is associated with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). We retrospectively investigated 22 patients with PM/DM-ILD (10 positive for anti-ARS Ab and nine positive for anti-MDA5 Ab) for whom antibody analysis of conserved serum was possible. We assessed mortality in the first three months as the therapeutic response in the acute phase and compared changes in clinical data for up to one year considered as the chronic phase. We classified the clinical changes over the year into three groups: Improvement (increased % vital capacity [%VC] or diffusing capacity of the lung for carbon monoxide [%DLCO]≥10 or 15%), deterioration (decreased %VC or %DLCO≥10 or 15%), and no change (remainder of the changes). The extent of abnormality demonstrated by high-resolution computed tomography (HRCT) was scored. Positivity for anti-MDA5 Ab, but not for anti-ARS Ab, was associated with mortality in the first 3 months. Evaluation of the therapeutic response in the first year showed that positivity for the anti-ARS Ab, but not for the anti-MDA5 Ab, was associated with an improvement in %DLCO and a decline in the serum KL-6 levels. Positivity for the anti-ARS Ab or negativity for anti-MDA5 Ab was associated with a greater decrease in bronchial dilatation as seen by HRCT. Anti-ARS and anti-MDA5 Abs are associated with the therapeutic response of PM/DM-ILD.

The impact of dihydropyrimidine dehydrogenase expression in pancreatic cancer patients who undergo curative resection with S-1 adjuvant chemotherapy

The antimetabolite drug, 5-fluorouracil (5-FU), is used in the treatment of various cancers, including basal cell carcinomas (BCCs). The authors hypothesized that keratocystic odontogenic tumors (KOTs) would respond to 5-FU treatment because of their similarities to BCCs in molecular etiopathogenesis.An ambispective cohort study of the treatment efficacy of topical 5-FU on KOTs was conducted. Independent variables included the topical application of 5% 5-FU or modified Carnoy's solution (MC) after enucleation and peripheral ostectomy at the University of Toronto from 2006 through 2014. Outcome variables included time to recurrence and peripheral nerve injury. KOT specimens in these patients were immunostained with p53, Ki-67, thymidylate synthetase (TS), thymidylate phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) antibodies. Semiquantitative staining scores were calculated for all immunohistochemistry sections examined. Descriptive statistics were computed using Fisher exact test and Kaplan-Meier analysis as appropriate with the P value set at .05.Thirty-two patients with 32 KOTs were reviewed (41% in women and 59% in men). There were no KOT recurrences in the 5-FU group (n = 11), whereas there were 4 recurrences in the MC group (n = 21; P = .190). There was a significantly lower incidence of inferior alveolar nerve paresthesia with 5-FU treatment (P = .039). Immunohistochemical staining showed upregulation of TP (P < .0001) and DPD (P < .0001) and no change in TS (P > .05) in inflamed KOTs.5-FU effectively treats KOTs with less postoperative morbidity than conventional treatment with MC. Low TS and upregulated TP expressions in inflamed KOTs suggest increased 5-FU efficacy in inflamed KOTs. Topical 5-FU is a novel therapy for KOTs and provides a targeted molecular approach to treatment.

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 subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52

Objective: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52.Methods: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed.Results: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119).Conclusions: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.

Effect of Müller cells on the survival and neuritogenesis in retinal ganglion cells

ObjectiveRetinal ganglion cells (RGCs) are the first affected cells in neuropathies like glaucoma, for that reason it is very important to explore new methods to neuroprotect these neurons. Müller cells are glial cells that provide the neurons with trophic factors and scaffold. The purpose of this study was to analyze the effect of Müller cells on survival and neurite formation in RGCs. MethodRat Müller cells were grown until a confluent culture on which rat RGCs were added, using pure culture of rat RGCs as controls. RGCs were labeled with βIII-tubulin, and Müller cells with glutamine synthetase antibodies. In addition, nuclei were stained with DAPI. The number of RGCs and number and neurite length were measured. ResultsNo differences were found in the number of RGCs between control and cells grown on the substrate of Müller cells. The proportion of RGCs with neurites increased when they grew on Müller (RGCs with 1–3 neurites increased from 19% to 43%. The length of neurites also increased in RGCs grown on Müller cells, with the number of RGCs with neurites from 50 to 200μm increasing from 21% to 41%, and with neurites of more than 200μm the increase was from 6% to 20%. ConclusionsMüller cells support the survival of RGCs and induced an increase in the number and length of neurites of RGCs.

Efecto de las células de Müller en la supervivencia y neuritogénesis de las células ganglionares de la retina

OBJECTIVERetinal ganglion cells (RGCs) are the first affected cells in neuropathies like glaucoma, for that reason it is very important to explore new methods to neuroprotect these neurons. Müller cells are glial cells that provide the neurons with trophic factors and scaffold. The purpose of this study was to analyze the effect of Müller cells on survival and neurite formation in RGCs. METHODRat Müller cells were grown until a confluent culture on which rat RGCs were added, using pure culture of rat RGCs as controls. RGCs were labeled with βIII-tubulin, and Müller cells with glutamine synthetase antibodies. In addition, nuclei were stained with DAPI. The number of RGCs and number and neurite length were measured. RESULTSNo differences were found in the number of RGCs between control and cells grown on the substrate of Müller cells. The proportion of RGCs with neurites increased when they grew on Müller (RGCs with 1-3 neurites increased from 19% to 43%. The length of neurites also increased in RGCs grown on Müller cells, with the number of RGCs with neurites from 50 to 200μm increasing from 21% to 41%, and with neurites of more than 200μm the increase was from 6% to 20%. CONCLUSIONSMüller cells support the survival of RGCs and induced an increase in the number and length of neurites of RGCs.

In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome.

Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P < 0.0001). The number of swollen joints was significantly higher (7.0 ± 5.0 vs 2.9 ± 3.9, P < 0.005), with a distribution resembling that of RA. Radiographic damages were also more frequent in ACPA-positive ASS patients (87% vs 11%, P < 0.0001). Aside from a significantly higher transfer factor for carbon monoxide in ACPA–ASS patients, lung, muscle, and skin involvements had similar incidences, patterns, and severity in both groups. Although Nonbiologic treatments were similarly used in both groups, ACPA-positive patients received biologics more frequently (59% vs 12%, P < 0.0008), mostly due to refractory arthritis (n = 9). Eight patients received anti-Cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) with good efficacy and tolerance, whereas 2 of the 5 patients treated with antitumor necrosis factor drugs had worsened myositis and/or interstitial lung disease. After a >7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements.

Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis

The study aims to comprehensively assess the profiles of myositis-specific autoantibodies (MSAs) in Chinese patients with polymyositis (PM)/dermatomyositis (DM) and compare them with a Japanese cohort. One hundred forty-five Chinese patients (68 classic DM, 25 clinically amyopathic DM [CADM], and 52 PM) and 165 Japanese patients (56 classic DM, 52 CADM, and 57 PM) were recruited. MSAs were measured with immunoprecipitation, enzyme-linked immunosorbent assay, or immunoprecipitation-immunoblotting. MSA frequencies were compared. The overall frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was significantly higher in the Chinese patients than in the Japanese cohort (36.6 % [53/145] versus 15.8 % [26/165], respectively, P < 0.001), whereas the frequencies of anti-signal recognition particle (SRP) antibodies (1.4 % [2/145] versus 7.9 % [13/165], respectively, P = 0.008) and anti-aminoacyl-transfer RNA synthetase (anti-ARS) antibodies (27.6 % [40/145] versus 40 % [66/165], respectively, P = 0.02,) were significantly lower. The significantly lower frequency of anti-ARS antibodies and significantly higher frequency of anti-MDA5 antibodies in the Chinese patients were observed in the classic DM subset (14.7 % [10/68] versus 46.4 % [26/56], respectively, P < 0.001, and 45.6 % [31/68] versus 5.4 % [3/56], respectively, P < 0.001) and CADM subset (8.0 % [2/25] versus 28.8 % [15/52], respectively, P = 0.04, and 88.0 % [22/25] versus 44.2 % [23/52], respectively, P = 0.0002), but not in the PM subset. The first detailed profile of MSAs in Chinese patients with PM/DM was established. The differences in MSA frequencies in the Chinese cohort and Japanese cohort suggest underlying genetic and/or environmental differences between these two populations. Key Messages • A significantly higher frequency of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was observed in Chinese patients with polymyositis/dermatomyositis (PM/DM) than in Japanese patients. • Our findings suggest that distinct genetic and/or local environmental factors affect Chinese and Japanese patients with PM/DM, who have been considered a "homogeneous" population in previous studies.

Mechanic’s hands in a woman with undifferentiated connective tissue disease and interstitial lung disease – anti-PL7 positive antisynthetase syndrome: a case report

IntroductionInterstitial lung disease can be idiopathic or occur in the setting of connective tissue diseases. In the latter case it requires a different treatment approach with a better prognosis. Interstitial lung disease can precede the onset of typical connective tissue disease features by many years, and therefore meticulous multidisciplinary follow-up is crucial. This case highlights the diagnostic challenge and the need for intensified attention for subtle clinical features when faced with interstitial lung disease in patients with characteristics of a hitherto undifferentiated connective tissue disease.Case presentationA 44-year-old Caucasian woman presented to our pulmonology department with dyspnea, Raynaud’s phenomenon and subtle swelling of fingers and eyelids. Laboratory analysis and autoantibody screening was negative. She was diagnosed with nonspecific interstitial pneumonia with a concurring undifferentiated connective tissue disease. After four years of stable disease, she presented with rapid pulmonary deterioration, myalgia, periorbital edema, arthritis and a cracked appearance of the radial sides of the fingers of both her hands. This clinical sign was recognized as mechanic’s hands and a specific search for the presence of antisynthetase antibodies was performed. She was found to harbor anti-threonyl-tRNA synthetase antibodies. A diagnosis of antisynthetase syndrome was made and she was treated with glucocorticoids and immunosuppressives.ConclusionsThis case highlights the difficulty in fine-tuning the diagnosis when confronted with a patient with interstitial lung disease and the suspicion of an underlying, yet undifferentiated connective tissue disease. There is a strong need for clinical multidisciplinary follow-up of these patients, with a high level of alertness to rare and specific clinical signs. The diagnosis of the underlying connective tissue disease profoundly influences the management of the interstitial lung disease. Recent data stress that identification of the autoantibody specificity allows for further prognostic stratification and therefore should be pursued.

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.

Biomarkers and Autoantibodies of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies.

Various autoantibodies are seen in idiopathic inflammatory myopathies. Among myositis-specific antibodies, anti-aminoacyl-tRNA synthetase and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are associated with interstitial lung disease (ILD). Anti-MDA5 antibodies are associated with dermatomyositis (DM) or clinically amyopathic DM complicated with rapidly progressive ILD. In anti-MDA5-positive patients, a random ground-glass attenuation pattern is a characteristic finding of ILD in chest high-resolution computed tomography. Conversely, anti-aminoacyl-tRNA synthetase antibodies are not associated with rapidly progressive ILD but with chronic ILD. DM or clinically amyopathic DM patients with anti-MDA5, and characteristic high-resolution computed tomography findings are highly likely to have devastating ILD and need aggressive treatment.