Anamika Kumari Anuja

Background Serum ferritin has been proposed as biomarker of interstitial lung disease (ILD) in anti-MDA5 dermatomyositis (DM). Nevertheless, no data exist for serum ferritin in other idiopathic inflammatory myopathies (IIM)-ILD nor in IIM without ILD. Aim of this case–control study was to assess whether serum ferritin may be considered a specific and sensitive biomarker for IIM-ILD, as well as to assess whether it correlates with clinical and immunological findings. Patients and methods All patients affected by IIM and followed at Siena (Italy), Palermo (Italy), Bari (Italy) and Lucknow, (India) IIM referral centers were retrospectively included. They had diagnosis of DM and ASS, with and without ILD. Myositis specific or myositis associated antibodies were tested through line immunoassay (Euroimmune, Lubeck, Germany). Serum ferritin concentrations at the first assessment (T0) were detected by ChemiLuminescent Enzyme Immunoassay technology. Results A total of 139 IIM patients (study cohort n = 51 and validation cohort n = 88; mean age and standard deviation 44.3 ± 17.75) were included. The most common subtype was DM (n = 70, 50.3%), followed by ASS (n = 50, 35.9%). The three most common MSAs were MDA5 (n = 25, 18%), Jo1 (n = 25, 18%) and Mi2 (n = 10, 7%). ILD was assessed in 69 subjects. Ferritin values were higher in DM-MDA5 than DM-non-MDA5 (p = 0.0073) and ASS (p = 0.0006). All 69 patients affected by ILD were subsequently divided showing statistically significant difference for ferritin (p = 0.0013). Conclusion Our study included a huge number of patients from multicenter datasets, comprising patients of different ethnicities. Ferritin values lower than 303.5 ng/ml evaluated for the first time in a patient with suspected IIM and ILD, waiting for autoimmunity tests, allowed to exclude MDA5-DM. The strength of our findings was corroborated by binomial logistic regression, which proved the independence of ferritin from CPK and CRP to identify DM-MDA5-ILD. Such evidence allows to exclude that ferritin values are influenced by systemic inflammation.

Introduction: Majority of available protocols for isolation of chondrocytes from articular cartilage tissue rely on the enzymatic digestion of the tissue by collagenase type 2. The yield of chondrocytes in such protocols is low. Herein, we designed a novel indigenous sequential digestion by dual enzyme Pronase and Collagenase Type 1 for isolating human Chondrocytes from articular cartilage. Methods: Articular cartilage of Osteoarthritis (OA) patients undergoing total knee replacement were collected for the isolation of chondrocyte cells and subjected to sequential digestion by Pronase for three hours followed by Collagenase 1 overnight. Pellet of cells collected after digestion was plated on culture flask in 5% CO₂ incubator. Results: From day three onwards, round to elongated cells adhered to the flask were visible which developed into elongated cell population of homogenous morphology, expressed Aggrecan (Agg), Collagen 2a (Col2a) and SRY-box transcription factor (Sox9) and had chondrogenic differentiation similar to a commercially available healthy chondrocyte. These cells were negative for Alizarin red stain, thus confirming the purity of chondrocytes. Conclusion: We have successfully established a sequential dual enzyme digestion-based culture technique for isolating the human chondrocytes from the articular cartilage biopsy derived from OA knee joints.

Objectives Primary objectives estimated prevalence of traditional cardiovascular disease (CVD) risk factors and compared different CVD risk prediction algorithms in an Indian rheumatoid arthritis (RA) population. Secondary objectives evaluated associations between carotid intima-media thickness (CIMT) and subclinical atherosclerosis (SCA) with CVD risk factors and CVD risk scores. Methods The presence of CVD risk factors were recorded, and 10-year CVD risk was predicted using Framingham risk scoring (FRS) using lipids (FRS-Lipids), FRS using body mass index (FRS-BMI), QRISK-2, SCORE, and the algorithm recommended by ACC/AHA (ASCVD). CIMT was measured on the far-wall of the common carotid artery. Subclinical atherosclerosis was defined as CIMT > 0.9 mm or the presence of carotid plaque. Results A total of 332 patents were enrolled, 12% had diabetes mellitus, 21.4% hypertension, and 6.9% were current/past smokers. Proportions of RA with predicted 10-year CVD risk > 10% varied from 16.2 to 41.9% between scores. Highest magnitude of risk was predicted by FRS-BMI. Agreement between scores in predicting risk was moderate in general. Mean CIMT was 0.70 ± 0.15 mm. Age, male sex, and extra-articular manifestations associated with greater CIMT. All risk scores except SCORE moderately correlated with CIMT. About one-seventh had SCA defined as CIMT > 0.9 mm or the presence of carotid plaques, associated with increasing age, male gender, or higher ratio of total cholesterol to high-density lipoprotein cholesterol. ASCVD and QRISK-2 scores had maximum area under curve for distinguishing SCA. Conclusion Individual CVD risk scores predict 10-year CVD risk differently in Indian patients with RA, and require validation for predicting hard end points (CVD events, mortality). Key Points • Diabetes mellitus and hypertension are the most prevalent cardiovascular disease risk factors in Indian patients with RA. • Individual cardiovascular risk prediction scores predict risk differently in Indian patients with RA, highest risk being predicted by the FRS-BMI. • Carotid intima-media thickness in RA associated with increasing age, male sex and extra-articular manifestations. • 14% RA had subclinical atherosclerosis, associated with increasing age, male sex, and higher total cholesterol to HDL-C ratio, best distinguished by ASCVD and QRISK-2 scores.

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.

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.