UNASSIGNED: Clinical guidance on the identification and management of connective tissue disease-associated interstitial lung disease (CTD-ILD) is needed for optimal clinical practice. We aimed to develop clinical algorithms for identifying and managing three common CTD-ILDs: those associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD).
UNASSIGNED: Meetings were held October - November 2023 to create consensus-based algorithms for identifying and managing SSc-ILD, RA-ILD, and PM/DM-ILD in clinical practice, based on expert consensus statements for identification and management of CTD-ILD previously derived from a Delphi process.
UNASSIGNED: We developed clinical algorithms for SSc-ILD, RA-ILD, and PM/DM-ILD that highlight both commonalities and differences in the identification and management of these CTD-ILDs. Importantly, ILD should be suspected in patients with SSc, RA, or PM/DM who have respiratory symptoms. Chest high-resolution computed tomography has utility for screening, diagnosis and assessment of severity. Furthermore, regular follow-up and multidisciplinary management are important. Disease-specific considerations include unique risk factors such as anti-topoisomerase I antibodies in SSc-ILD, high-titer cyclic citrullinated peptide antibodies in RA, anti-aminoacyl tRNA synthetase antibodies in PM/DM, and anti-melanoma differentiation-associated gene 5 antibody in DM.
UNASSIGNED: These algorithms may help physicians to identify and manage patients with SSc-ILD, RA-ILD, or PM/DM-ILD.

OBJECTIVE: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption.
METHODS: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing.
RESULTS: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets.
CONCLUSIONS: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

UNASSIGNED: Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to acute hypercapnic respiratory failure, posing significant challenges in management.
UNASSIGNED: Our patient is a 73-year-old male with a history of polymyositis, who presented with acute hypercapnic respiratory failure secondary to a suspected polymyositis flare. Despite initial management, the patient experienced complications, including dysphagia, thrombocytopenia, and altered mental status. Neurological consultations revealed conflicting opinions regarding the primary diagnosis, suggesting inclusion body myositis. The patient\'s condition continued to deteriorate, prompting discussions about prognosis and palliative care options. This case highlights the challenges in managing respiratory failure in patients with late-onset nemaline myopathy and the importance of multidisciplinary care in addressing complex medical needs.
UNASSIGNED: This case emphasises the complexity of managing respiratory failure in patients with late-onset nemaline myopathy and the significance of adopting a multidisciplinary approach. Timely interventions, including respiratory support, dysphagia management, and palliative care discussions, are vital in optimizing patient care and quality of life. Further research is warranted to elucidate optimal management strategies and improve outcomes in this patient population.

Idiopathic inflammatory myopathies (IIM) are rare diseases (incidence 1:100,000) with a wide range of clinical symptoms and manifestations. Typical indicators of IIM are proximally emphasized muscle weakness and myalgias, which are usually accompanied by elevated creatine kinase levels and muscle atrophy. The autoantibody diagnostics separate IIM into different entities, which are each associated with a typical risk of organ manifestations and the occurrence of tumors. The IIM represents an interdisciplinary challenge and the diagnostics and treatment require the involvement of several disciplines including rheumatology, neurology, neuropathology, dermatology and pneumology. An accurate diagnosis and careful tumor screening are essential because of the association between certain subgroups of IIM and the occurrence of malignant tumors.
UNASSIGNED: Idiopathische inflammatorische Myopathien (IIM) gehören zu den seltenen Erkrankungen (Inzidenz 1:100.000) mit stark variierender Symptomatik und vielfältigen Manifestationen. Leitsymptome der IIM sind die proximal betonte Muskelschwäche und Myalgien, die in der Regel mit einer Erhöhung der Kreatinkinase und Muskelatrophie einhergehen können. Die Autoantikörperdiagnostik trennt die IIM in unterschiedliche Entitäten, die mit einem jeweils typischen Risiko an Organmanifestationen und Auftreten von Tumoren assoziiert sind. Sie stellen eine interdisziplinäre Herausforderung dar und bedürfen in Diagnostik und Therapie unter anderem der Disziplinen Rheumatologie, Neurologie, Neuropathologie, Dermatologie und Pneumologie. Aufgrund der Assoziation zwischen bestimmten Subgruppen der IIM und malignen Tumoren sind eine präzise Diagnose und angemessene Tumorsuche von großer Bedeutung.

Overlapping autoimmune disorders are used to describe the coexistence of more than one autoimmune disease in the same patient. Mixed connective tissue disease (MCTD) and anti-synthetase syndrome (ASS) are autoimmune diseases that manifest with pulmonary involvement, presenting as persistent dyspnea. The coexistence of both conditions in the same patient is extremely rare. We herein report a case of a 44-year-old female who was diagnosed with MCTD with features of ASS (anti-Jo-1 antibody) in the setting of rheumatoid arthritis (anti-cyclic citrullinated peptide (anti-CCP) antibody), which shows temporary breathing improvement following treatment with corticosteroid and mycophenolate mofetil. However, after the completion of mycophenolate mofetil, she was found to be anti-Jo-1 antibody negative and anti-CCP antibody positive. Our case emphasizes the need to recognize overlapping autoimmune conditions in patients with complex clinical features and presentations with the immediate application of a comprehensive diagnostic approach and tailored treatment strategies. Early diagnosis and aggressive treatment are crucial for achieving remission and preventing organ damage.

OBJECTIVE: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM).
METHODS: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups.
RESULTS: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren\'s syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups.
CONCLUSIONS: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM.

UNASSIGNED: MicroRNAs (miRNAs) represent a new class of biomarkers in the context of connective tissue disorders. The miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with polymyositis (PM) and dermatomyositis (DM) have not been fully elucidated. The objective is to investigate miRNAs expression profile in PBMCs of patients with PM/DM.
UNASSIGNED: Microarray technology was used to identify differentially expressed miRNAs in PBMCs obtained from 6 untreated PM/DM patients and 3 healthy controls (HCs). TaqMan-based stem-loop real-time PCR detection was used for validation in a cohort of 34 PM/DM patients and 20 HCs.
UNASSIGNED: Microarray analysis revealed 38 differentially expressed miRNAs (24 up-regulated and 14 down-regulated) in PM/DM patients compared to HCs. Four miRNAs (miR-320a, miR-335-3p, miR-34a-5p and miR-454-3p) were chosen for real-time PCR validation. The expression of miR-34a-5p was significantly upregulated in PM/DM group (P < 0.05). In subgroup analysis, miR-34a-5p was significantly upregulated in interstitial lung disease (ILD) group and DM group (P < 0.001). The level of SIRT1, a validated target of miR-34a, was significantly lower in PBMCs of PM/DM patients compared with HCs.
UNASSIGNED: MiR-34a-5p may potentially participate in the pathogenesis of PM/DM through SIRT1, and may serve as a potential new biomarker for PM/DM-ILD.

暂无摘要。

UNASSIGNED: Inflammatory myopathy with mitochondrial pathology (IM-Mito) is a rare condition described in a few case series, and it is not clear whether it is a specific disease or a variant of Inclusion Body Myositis (IBM). Radiological data of IM-Mito patients has only been evaluated in one study.
UNASSIGNED: To analyze whole-body muscle magnetic resonance imaging (MRI) features in patients with IM-Mito compared with individuals with IBM.
UNASSIGNED: Fourteen IM-Mito and ten IBM patients were included. IM-Mito was defined by endomysial inflammatory infiltrate, presence of at least 1% of Cytochrome C Oxidase negative fibers, and absence of rimmed vacuoles in muscle biopsy; and IBM was defined by the presence of dystrophic muscular abnormalities, endomysial inflammatory infiltrate, and rimmed vacuoles. Patients underwent clinical evaluation and whole-body muscle MRI to determine the presence of edema, and fatty infiltration in various muscles.
UNASSIGNED: Muscle imaging abnormalities were asymmetric in most patients with IM-Mito and IBM. Muscles with the highest average degree of fatty infiltration in both conditions were the quadriceps and medial gastrocnemius. Most patients with IM-Mito and IBM showed imaging patterns of rectus femoris relatively spared compared to other quadriceps muscles. The flexor digitorum profundus was the most affected muscle of the upper limbs in both IBM and IM-Mito.
UNASSIGNED: Although the results suggest some similarities in muscle imaging features between IM-Mito and IBM, there remains uncertainty whether these two conditions are part of the same clinical spectrum.

OBJECTIVE: Creatine kinase (CK) and aldolase are markers traditionally used in the study of muscle damage (MD). As CK determination is more specific to muscle damage, the demand for both determinations in routine laboratory tests would entail an extra cost.
METHODS: Retrospective observational study conducted between 2019-2020. CK and aldolase concentrations from 218 patients were studied.ROC curves were analyzed for CK and aldolase for muscle damage detection. Cut-off values were selected for both strategies. Specifity of CK and aldolase for dermatomyositis or polymyositis diagnosis in our population was studied using the McNemar\'s test.
RESULTS: The area under the ROC curve (AUC) for total CK was 0.716 (95%CI: 0.651-0.775), for CK in males it was 0.703 (95%CI: 0.592-0.799), and for CK in females was 0.719 (95%CI: 0.636-0.793). For aldolase, AUC was 0.505 (95%CI: 0.437-0.573). Optimized cut-off points for each determination were: 112 U/L for CK in men, with a sensitivity of 73.9% (95%CI: 51.6-89.8) and a specificity of 49.2% (95%CI: 35.9-62.5); 88 U/L for CK in women, with a sensitivity of 75.0% (95%CI: 57.8-87.9) and specificity of 50.5% (95%CI: 40.4-60.6); and 5.6 U/L for aldolase, with a sensitivity of 61.0% (95%CI: 53.2-68.8) and a specificity of 38.8% (95%CI: 26.5-52.6).Regarding the individuals diagnosed with dermatomyositis or polymyositis, 66.7% and 44.4% of them were correctly classified as pathological by CK and aldolase results, respectively. McNemar\'s test did not reveal significant differences.
CONCLUSIONS: The determination of CK offers a better diagnostic performance of MD and, in addition, does not present significant differences regarding the determination of aldolase in cases of polymyositis and dermatomyositis. Therefore, the single determination of CK would be sufficient for MD screening.