Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis

BackgroundThe Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA).ObjectivesTo evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM.MethodsAdult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed.ResultsMSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age [40 (30^–49), 13 (7.5–16) years] and disease duration [ 7 (3–17), 6 (2–17) months] comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children.ConclusionMyositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive.     

Myositis-specific autoantibodies in adults with idiopathic inflammatory myopathy: correlations with diagnosis and disease activity

Clinical Rheumatology - To determine the relationship of myositis autoantibodies with the diagnosis and severity of idiopathic inflammatory myopathy (IIM) using the 2017 EULAR/ACR idiopathic...     

Differentiating idiopathic inflammatory myopathies from metabolic myopathies

The metabolic myopathies are a heterogeneous group of diseases, including glycogenoses, disorders of lipid metabolism, and mitochondrial myopathies, that result primarily from inborn errors of metabolism. Most of these metabolic defects cause medical conditions that manifest early in life. Nevertheless, clinical presentations during the teenage years and adulthood are increasingly being recognized. Many of the clinical manifestations of these diseases are difficult to differentiate from those observed in the idiopathic inflammatory myopathies, especially polymyositis. A directed evaluation using the clinical, laboratory, and genetic approaches summarized in this article, however, should allow for the differentiation of most metabolic myopathies from polymyositis and other forms of idiopathic inflammatory myopathy. The diagnosis of a metabolic myopathy should be considered in patients who appear to have polymyositis but lack the characteristic changes of inflammation found on EMG, MRI, or muscle histology, or in such patients who are refractory to immunosuppressive therapy. The forearm ischemic exercise test is especially useful to screen for some inborn errors of glycogen metabolism or glycolysis and for myoadenylate deaminase deficiency. Thorough analysis of muscle tissue, including histology, histochemistry, biochemistry, and occasionally electron microscopy, is often necessary to make the diagnosis of a metabolic myopathy. Advances in molecular biology methods and knowledge of the precise genetic defects associated with these metabolic defects are dramatically increasing our capacity to diagnose patients with a widening range of myopathies. It is expected that, with further understanding of the mechanisms of the metabolic and idiopathic inflammatory myopathies, the differentiation of these disorders into their pathogenetic components, and the capacity to diagnose them will continue to improve. These are essential factors in improving genetic counseling and eventually the therapy of these serious, and currently incurable, disorders.     

The spectrum and clinical significance of myositis-specific autoantibodies in Chinese patients with idiopathic inflammatory myopathies

Clinical Rheumatology - The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients...     

Myositis autoantibody profiles and their clinical associations in Greek patients with inflammatory myopathies

Clinical Rheumatology - Myositis-specific (MSAs) or-associated autoantibodies (MAAs) have been linked to particular clinical phenotypes of idiopathic inflammatory myopathies (IIM) and appear to aid...     

Myositis-specific and myositis-associated autoantibodies in Indian patients with inflammatory myositis

We aimed to study the prevalence and clinical associations of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in a large cohort of Indian patients with idiopathic inflammatory myositis (IIM). Clinical details and serum samples were collected from patients with IIM (satisfying Bohan and Peter Criteria, 1975) and CTD-associated myositis. Sera were analysed for antibodies against SRP, Mi2, Jo1, PL7, PL12, EJ, OJ, Ro52, Ku, Pm-Scl 75 and PM-Scl 100, using immunoblot assay. The cohort comprised 124 patients with IIM (M:F = 1:3.6). Fifty-five of them had dermatomyositis (DM), 22 had juvenile dermatomyositis (JDM), 25 had polymyositis (PM) and 22 had connective tissue disease-associated myositis (CTD myositis). Mean disease duration was 10.9 months. ANA was positive in 84 (68.9 %), and MSAs in 61 (49.2 %) patients. Among MSAs, autoantibodies to Mi2, synthetase (Jo1, PL7, PL12, EJ) and SRP were present in 26 (20.9 %), 29 (23.4 %) and 6 (4.8 %) patients, respectively. Prevalence of MAAs was as follows: antibodies to Ro52 in 45 (36.3 %), Ku and PM-Scl 75 in 13 (10.5 %) and PM-Scl 100 in 5 (4 %) patients. Anti-Mi2 antibodies were positively associated with DM (21/55, 38.2 %; p < 0.0001) and pharyngeal weakness (13/34, 38.2 %; p = 0.004) and negatively associated with ILD (0/28; p = 0.001). ILD and mechanics’ hands were significantly more in patients with anti-synthetase antibodies (16/28, 57 % and 14/22, 63.6 %; p < 0.0001). Four of six patients with anti-SRP antibody showed poor response to multiple drugs. Higher prevalence of anti-Mi2 is probably related to higher proportion of patients with DM. Absence of ILD in patients with anti-Mi2 antibody suggests that it may protect against ILD. In Indian population also, anti-synthetase antibodies are associated with ILD, and anti-SRP antibodies with poor response to treatment.     

The association between myositis-specific autoantibodies and muscle pathologies in idiopathic inflammatory myopathies

Clinical Rheumatology - To investigate specific muscle pathologies of different kinds of myositis-specific autoantibodies (MSAs) in idiopathic inflammatory myopathy (IIM) patients. One hundred...     

The clinical associations of mitotic spindle autoantibodies in a South Australian cohort

Background: The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. Aims: As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. Methods: All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control group of consecutive ANA positive, anti-MSA negative individuals had anti-thyroid antibodies measured. Statistical comparison used χ² test. Results: Fifty-five subjects (43F) were identified with mean age 59.8 (range 17–91); 39 had specific diagnoses, with 16 identified as part of non-specific investigations. ‘Arthritis’ broadly accounted for the largest group, transient inflammatory arthritis n=7, degenerative joint disease n=6, rheumatoid arthritis n=5. Adenocarcinoma and mesothelioma accounted for one case each. Thirty-two subjects had anti-thyroid antibodies tested, with ten of 21 and two of 11 positive among the groups with anti-MSA titre >1:80 and <1:40 respectively, χ²=2.7, p=0.1. Anti-thyroid antibodies were detected more frequently among the high titre anti-MSA group (ten of 21) compared with high titre positive ANA, negative anti-MSA group (two of 11), RRisk 4.4, χ²=5.34, p=0.02. Conclusion: This study confirmed the relative rarity of anti-MSA and that its association is primarily with rheumatic diseases. The coincidence of mesothelioma is novel with only two previous reports of malignancy and anti-MSA. The co-association of high titre anti-MSA and thyroid autoantibodies suggest that the latter should be a follow up investigation if the former is identified as part of an investigative screen.     

Familial autoimmunity and the idiopathic inflammatory myopathies

Many lines of evidence suggest that autoimmune diseases result from chronic immune activation following environmental exposures in genetically susceptible individuals. A genetic basis for autoimmunity is supported by twin and family studies, candidate gene investigations, animal models, and whole genome microsatellite scans. These findings predict, and clinical observations support, familial clustering of a number of individual autoimmune diseases, notably lupus, multiple sclerosis, type-1 diabetes mellitus, rheumatoid arthritis, and recently the idiopathic inflammatory myopathies. Yet, not only is the same autoimmune disease increased in prevalence in pedigrees of persons affected with a given disorder, but other autoimmune diseases are as well. We review these data and propose a hypthesis consistent with these findings. This model posits that a rheumatic disease, as currently classified, is actually composed of a number of elemental disorders. Each of these is defined by the minimal necessary and sufficient environmental exposures and genes that result in a pathology leading to a given sign-symptom complex.     

Diagnosis and classification of idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis‐specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti‐SRP and anti‐HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables.     

Myositis-specific autoantibodies: overview and recent developments.

Myositis-specific autoantibodies (MSAs) are found in almost half the patients with an idiopathic inflammatory myopathy (IIM). Several clinical and epidemiological studies have suggested that MSAs are associated with specific clinical characteristics. Some of these associations are well-defined and are of clinical significance ( eg, anti-Jo-1 and the anti-synthetase syndrome), others are less well established and can cause unnecessary anxiety for both patients and physicians ( eg, anti-SRP and cardiac involvement). In this review, an overview is given of the various MSAs, their biochemical background, their clinical usefulness, and the promises they hold for a better understanding of IIM.     

Performance of the 2017 EULAR/ACR criteria for idiopathic inflammatory myopathies in a cohort of patients from Latin America

We aimed to determine the performance of the 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) in a cohort of Chilean patients. This single-center retrospective study included 151 patients with a clinical diagnosis of IIM. Patients were classified according to the 2017 EULAR/ACR classification criteria for IIM, and its performance was compared to the Bohan & Peter (B&P) classification criteria. A total of 135 patients (89.4%) met the EULAR/ACR criteria, and 140 (92.7%) patients met the B&P criteria. A total of 130 patients had IIM according to both the criteria; concordance rate was 29.2% for definite IIM, 6.2% for probable IIM, and 1.5% for possible IIM. The kappa coefficient of agreement was weak between the 2 classification criteria (κ = 0.39, SD 0.15–0.64). Against gold standard expert physician’s diagnosis, sensitivity, and specificity of EULAR/ACR criteria was 0.86 and 0.85 to diagnose dermatomyositis, respectively, and 0.73 and 0.87 to diagnose polymyositis. The EULAR/ACR criteria showed good sensitivity and identified more patients with probable or definite IIM than the B&P criteria in a single-center cohort of patients with IIM in South America. The sensitivity of the EULAR/ACR criteria was slightly higher in patients with dermatomyositis, but lower in patients with polymyositis, than that of the B&P criteria.     

High Frequencies and co-existing of myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies overlapped to rheumatoid arthritis

A small proportion of patients with rheumatoid arthritis (RA) develop idiopathic inflammatory myopathies (IIM); however, the clinical and immunological characteristics of these patients have not been elucidated. In the present study, we evaluate the frequency of autoantibodies and the accompanying clinical features in patients with IIM overlapped to RA (IIM-RA) and in patients with IIM without RA. Twelve patients with IIM-RA were selected from 142 patients with IIM who were admitted to our hospital. Clinical and laboratory data, including autoantibody test results, were collected from patient medical records. Myositis-specific antibodies (MSAs) were analyzed by immunoprecipitation. Clinically, patients with IIM-RA were more likely to be male, to have polymyositis, and to be older at the time of IIM onset than patients with IIM without RA. Patients with IIM-RA had been treated for 2–25?years prior to the onset of IIM with more than two disease-modifying antirheumatic drugs (DMARDs). Patients with IIM-RA had a high frequency (75.0%) of positivity for MSAs, including anti-Jo-1, anti-PL-7, anti-PL-12, or anti-signal recognition particle (SRP) antibodies; anti-Jo-1 antibody was detected in 4 patients (33.3%). In addition, 2 out of 12 patients with IIM-RA were concurrently positive for two different MSAs, anti-Jo-1, and anti-PL-7 antibodies. In 3 other patients with IIM-RA, anti-Jo-1 antibody, or anti-PL-7 antibody was detected in serum samples collected 6–18?months prior to development of myositis. High frequency and coexistence of MSAs were detected in patients with IIM-RA. MSAs detected in patients with RA even without symptoms of myositis may indicate possible future development of myositis.     

Trends in idiopathic inflammatory myopathies: cross-sectional data from the German National Database

Rheumatology International - To describe trends in outcomes among patients with idiopathic inflammatory myopathies (IIM) over two decades. From 1997 to 2017, a total of 1079 IIM patients were...