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This study aimed to determine the prevalence and clinical characteristics of anti-HMGCR antibodies in idiopathic inflammatory myositis (IIM) at a tertiary care centre in northern India. Data (adult and children) were retrieved from the MyoCite dataset, identifying patients with polymyositis, dermatomyositis, and antibody-negative IIM whilst fulfilling the ACR/EULAR criteria. SLE, sarcoidosis, and systemic sclerosis were included for comparison as disease controls. The baseline clinical profile, laboratory tests, and muscle biopsies were retrieved and analysed. Descriptive statistics and non-parametric statistics were used for comparison. Among 128 IIM (112 adults, 16 children, M:F 1:2.8) of age 37 (24-47) years and 6 (3-17) months disease duration, 4 (3.6%) young adults tested positive for anti-HMGCR antibodies. All children and disease control tested negative for the antibody. Anti-HMGCR + IIM exhibited higher muscle enzymes [AST (367 vs 104 IU/L, p = 0.045), ALT (502 vs 78 IU/L, p = 0.004), and CPK (12,242 vs 699 IU/L, p = 0.001] except lactate dehydrogenase with less frequent systemic features such as fatigue than antibody-negative IIM. One young girl presented with a Limb-girdle muscular dystrophy (LGMD) with chronic pattern. None of the patients exhibited rashes, statin exposure, or cancer, though one had anti-Ro52 and mild disease. Our observations depict a younger population while affirming previous literature, including NM-like presentation, and chronic LGMD-like pattern of weakness in one case. Although a small number of children were included, ours is one of the few paediatric studies that evaluated HMGCR antibodies thus far. Further investigations in a larger Indian cohort are warranted to substantiate our findings.
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Autoanticuerpos , Miositis , Acilcoenzima A , Adulto , Niño , Femenino , Humanos , Masculino , Miositis/epidemiología , Prevalencia , Sistema de Registros , Adulto JovenRESUMEN
INTRODUCTION: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. METHODS: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). RESULTS: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. CONCLUSION: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.
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Miositis , Sarcoidosis , Humanos , Autoanticuerpos , Biomarcadores , Inflamación , Estudios Longitudinales , Miositis/diagnóstico , Sarcoidosis/diagnósticoRESUMEN
AIMS: Anti-mitochondrial antibodies (AMAs) are associated with distinct clinical phenotypes including cardiac and hepatic manifestations in idiopathic inflammatory myopathies (IIMs). This article studies the prevalence, clinical characteristics and outcomes of AMA in Indian patients with IIM. METHODS: Patients (97: 81 adult, 16 juvenile) clinically diagnosed with polymyositis or antibody-negative IIM were retrieved from the MyoCite bio-archive. They were tested for myositis-specific autoantibodies / myositis autoantibodies (MSAs/MAAs) using line immunoassay and antinuclear antibodies and AMAs using immunofluorescence assay (IFA). Patients were also screened for cardiac biomarkers (cardiac troponin I [c-TnI] and N terminal-pro brain natriuretic peptide [NT-pro-BNP] using immunometric immunoassay technique and enhanced chemiluminescence assay testing respectively) and hepatic manifestations using AMA testing. Results were formulated after carrying out analytical tests. RESULTS: Of the cohort, 5 adults (6.2%) (M:F 0:1) with a median age and disease duration of 37 years and 2 months respectively, tested AMA+ while the children tested negative. Dermatomyositis was the commonest phenotype, with amyopathic forms being common, often with MSA positivity. Cancer-associated myositis and polymyositis were also seen. AMA positivity is associated with Gottron's sign and calcinosis. Comparable levels of C-TnI and NT-pro-BNP and AMA testing in patients help to rule out subclinical cardiac and hepatic involvement respectively. CONCLUSION: Anti-mitochondrial antibodies are rare (6.2%) in different subtypes of IIM in the Indian population, and often coexist with MSAs. Their negative association with cardiac and hepatic involvement and probable association with Gottron's sign and calcinosis merit further investigation and long-term follow-up to understand the entire spectrum of the disease.
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Calcinosis , Miositis , Polimiositis , Anticuerpos Antinucleares , Autoanticuerpos , Humanos , Miositis/diagnóstico , Miositis/epidemiología , Polimiositis/epidemiologíaRESUMEN
Objectives: Differentiating smoldering disease activity from weakness due to fatty replacement of atrophied muscle can often be a challenge in the idiopathic inflammatory myositis (IIM). We aimed to identify the metabolic disturbances associated with IIM and if these changes can aid in the assessment of disease activity. Methods: Metabolic profiles of sera (N = 99) and muscle (N = 21) from patients with IIM (ACR-EULAR criteria) were compared with healthy control (HC) samples (N = 75 for serum and N = 12 for muscle tissues) employing 800 MHz NMR (Nuclear Magnetic Resonance) spectroscopy. Metabolic disparity between IIM and HC was established based on Partial Least Squares Discriminant Analysis (PLS-DA) and the discriminatory metabolites were identified based on variable importance in projection (VIP) statistics (P-value < .05, corrected for false discovery rate (FDR)). Results: Serum metabolomics profiles were distinctive in IIM as compared to HC, with a visible shift to anaerobic metabolism (increased lactate, low glucose), oxidative defect (high Phenylalanine/tyrosine), decreased muscle mass (low serum creatinine), increased muscle catabolism (increased branched-chain amino acids), and dyslipidemia (higher lipids, higher very low-density lipoprotein [VLDL]/low-density lipoprotein [LDL] ratio, lower polyunsaturated fatty acid [PUFA]). The sera of active IIM patients were characterized by anaerobic metabolism (low glucose), loss of muscle mass (low creatinine, amino acids), and oxidative defect (high Phenylalanine/tyrosine). Three metabolites (isopropanol, succinate, and glycine) were distinctive in muscle tissue metabolomics. NMR-based serum metabolic disparity was lacking between different clinical subsets of IIM. Conclusion: Serum and muscle tissue metabolomics have the potential to distinguish (a) IIM from HC and (b) active IIM from inactive IIM irrespective of disease subtype.