Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Spirituality, Religiosity, and Mental Health in Patients with Idiopathic Inflammatory Myopathies: A Brazilian Multicentric Case-Control Study.

No published studies have investigated the correlation between religiosity, spirituality, mental health, and idiopathic inflammatory myopathy (IIM) or systemic autoimmune myopathy. Therefore, we aimed to evaluate the association between religiosity/spirituality, sociodemographic factors, and the mental health of IIM patients. This is a multicenter case-control study that included 151 patients with IIMs and 95 individuals without autoimmune diseases (controls), held between August 2022 and April 2023. This study used a semi-structured questionnaire that included sociodemographic information and the juxtaposition of the following questionnaires: the Attitudes Related to Spirituality Scale (ARES); the Duke University Religion Index (DUKE), which is composed of the organizational religious affiliation (ORA), non-organizational religious affiliation (NORA), and intrinsic religiosity (IR) domains; and the General Health Questionnaire-12 (GHQ-12). Data were analyzed using Epi Info software 7.2.5 (Centers for Disease Control and Prevention, Atlanta, GA, USA). A comparison between the mean values of the ARES, DUKE, and GHQ-12 scales was made using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. A logistic regression test was used with the variables whose difference was statistically significant in the univariate analysis. Correlation analysis was performed using the Spearman rho coefficient. A higher prevalence of evangelicals and a lower prevalence of Catholics (p < 0.050) were seen in the IIM group compared to controls. Positive association was demonstrated between IIMs and the pardo ethnicity (OR = 2.26, 95% CI = 1.20-4.25, p = 0.011), highest ORA (OR = 2.81, 95% CI = 1.53-5.15, p < 0.001), NORA (OR = 3.99, 95% CI = 1.94-8·18, p < 0.001), IR (OR = 5.27, 95% CI = 2.32-11.97, p < 0.001), and ARES values (OR = 1.08, 95% CI = 1.04-1.13, p < 0.001). Mental health levels were compared between the groups (p > 0.999). Therefore, higher levels of religiosity and spirituality were observed in the IIM group than in the control group, but there was a similar distribution of mental health levels. The following can be cited as advantages of the present study: (i) the large sample for a rare disease with the presence of a control group; (ii) the multicenter characteristic with participation from three regions of Brazil; (iii) being the first study to map aspects of religiosity, spirituality, and mental health in IIMs.

Hereditary motor and sensory neuropathy Okinawa type mimicking proximal myopathy.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P), or, Okinawa type, is a rare neuromuscular disorder characterized by proximal dominant neurogenic atrophy and distal sensory alterations with an autosomal dominant inheritance pattern. We present a case of a Brazilian woman of Okinawan ancestry, with symmetrical proximal weakness, fasciculations, absent patellar reflexes and positive familial history for the same symptoms. These findings led to genetic testing, which identified a variant in the TFG gene (c.854 C>T;p.(Pro285Leu), confirming the diagnosis of HMSN-P. HMSN-P seemed to be restricted to populations in Okinawa, however, other HMSN-P cases were described in several parts of the world, especially in South America. This case report emphasizes the importance of considering HMSN-P in patients presenting with clinical features resembling proximal myopathy, especially in individuals with Okinawan ancestry.

Novel B-cell subsets as potential biomarkers in idiopathic inflammatory myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double-negative subsets, as well as an expansion of the naive compartment relative to healthy controls, that contribute to defining disease-associated B-cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathy onset or development.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

External validation of the 2017 ACR/EULAR classification criteria for inflammatory myopathies in a Mexican cohort: Role of autoantibodies in the diagnosis and classification of patients with inflammatory myopathies.

OBJECTIVE: This retrospective study aimed to perform the first external validation of the ACR/EULAR classification criteria for inflammatory myopathy (IIM) in a Mexican dynamic cohort where the patients were evaluated with clinical and laboratory values. As secondary objectives, we presented the clinical characteristics of the patients and included antibodies other than anti Jo1 to evaluate their impact on our population. METHODOLOGY: This study included 70 patients with IIM and 70 patients with differential diagnoses of IIM, according to the absolute score of the classification criteria. We obtained sensitivity and specificity in the modality without biopsy, and as an exploratory analysis, we added other antibodies from the myositis extended panel. We analyzed the area under the curve (AUC) of three models: score without antibodies, with anti Jo1 and with any antibody. RESULTS: The ACR/EULAR criteria showed increased specificity and at least similar sensitivity to that of the original cohort (85% sensitivity and 92% specificity), with a cohort point of >55%. When we classified patients into definite, probable, possible, and no IIM categories, by adding the extended myopathy panel, 6 of the 10 patients initially classified as "no IIM" changed their classification to "Probable IIM" and 4 to "Definite IIM"; of the 16 patients classified as "probable IIM," 15 changed their classification to "Definite IIM." CONCLUSION: Considering the limitations of this study, we concluded that the 2017 EULAR/ACR criteria for IIM classification are sensitive and specific for classifying patients with IIM in the Mexican population. Additionally, the addition of antibodies other than anti-Jo1 may improve performance in certain populations.

An early onset benign myopathy with glycogen storage caused by a de novo 1.4 Mb-deletion of chromosome 14.

Early onset myopathies are a clinically and histologically heterogeneous monogenic diseases linked to approximately 90 genes. Molecular diagnosis is challenging, especially in patients with a mild phenotype. We describe a 26-year-old man with neonatal hypotonia, motor delay and seizures during infancy, and non-progressive, mild muscular weakness in adulthood. Serum Creatine kinase level was normal. Whole-body muscle MRI showed thin muscles, and brain MRI was unremarkable. A deltoid muscle biopsy showed glycogen storage. WGS revealed a de novo 1.4 Mb-deletion of chromosome 14, confirmed by Array-CGH. This microdeletion causes the loss of ten genes including RALGAPA1, encoding for RalA, a regulator of glucose transporter 4 (GLUT4) expression at the membrane of myofibers. GLUT4 was overexpressed in patient's muscle. Here we highlight the importance to search for chromosomal alterations in the diagnostic workup of early onset myopathies.

Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis.

Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs). Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared. Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPKß2, AS160, INSR, PGC1-α, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPKß2, AS160, INSR, PGC1-α, PI3K, and RAB14) and in IMNM group (AKT2, AMPKß2, RAB10, RAB14, and PGC1-α). Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases.

Patients with inflammatory myopathies overlapping with systemic sclerosis: A Brazilian-Japanese bicentric study.

Objectives: This study aims to describe and compare the demographic, clinical, and laboratory characteristics and follow-up of representative samples of patients with myopathies and systemic sclerosis overlap syndromes (Myo-SSc) from two tertiary centers. Patients and methods: This is a cross-sectional and retrospective study conducted between January 2000 and December 2020. Fourty-five patients were analyzed with Myo-SSc (6 males, 39 females; mean age: 50.2±15.4 years; range, 45 to 65 years) from two tertiary centers (n=30 from Brazil and n=15 from Japan). Results: The median follow-up was 98 (range, 37 to 168) months. Muscle impairment started simultaneously with the diagnosis of systemic sclerosis in 57.8% (26/45) of cases. Muscle involvement occurred before the onset of systemic sclerosis in 35.5% (16/45) of cases, and after in 6.7% (3/45). Polymyositis was observed in 55.6% (25/45) of cases, followed by dermatomyositis in 24.4% (11/45) and antisynthetase syndrome in 20.0% (9/45). Concerning systemic sclerosis, the diffuse and limited forms occurred in 64.4% (29/45) and 35.6% (16/45) of the cases, respectively. Comparing the subgroups, Myo or SSc onset was earlier in Brazilian patients, and they had a higher frequency of dysphagia (20/45, [66.7%]) and digital ulcers (27/45, [90%]), whereas Japanese patients had higher modified Rodnan skin scores (15 [9 to 23]) and prevalence of positive anti-centromere antibodies (4/15 [23.7%]). The current disease status and mortality were similar in both groups. Conclusion: In the present study, Myo-SSc affected middle-aged women, and its manifestation spectrum varied according to geographic distribution.

Characterization of patients with dermatomyositis in a university hospital in Colombia

Introduction: Dermatomyositis is an idiopathic inflammatory myopathy characterized by the presence of skin lesions; it is considered a heterogeneous disease, due to its clinical presentation, course, and prognosis. In Colombia there are few records that describe the clinical characteristics of these patients. Methods: Cross-sectional study. Medical records of patients who consulted a university hospital in Colombia between January 2004 and December 2019 were reviewed. The records were obtained using databases from the dermatology, rheumatology, dermatopathology, and electrophysiology units, and CIE10 diagnostic codes. Results: Seventy patients with a dermatomyositis diagnosis were found, 63 (90%) fulfilled the Bohan and Peter diagnostic criteria and 7 (10%) had amyopathic dermatomyositis, with an average age of 43 years (SD ± 15.3). Forty-eight were women (68.5%). The most frequent clinical signs were Gottron's papules 80%, periorbital violaceous (heliotrope) erythema with edema 78.5% (n = 55) and poikiloderma 75.7% (n = 53). The most frequently found systemic manifestations were dysphagia (21.4%, n = 15), interstitial lung disease (11.4%, n = 8), and pulmonary hypertension (8.5%, n = 6). Cancer was documented in 8.5% (n = 6) of patients. Conclusion: We showed clinical information of patients with dermatomyositis in a referral hospital in Colombia. The data obtained is consistent with information from other case series worldwide.

Introducción: La dermatomiositis es una miopatía inflamatoria idiopática que se caracteriza por presentar lesiones en la piel; por su presentación clínica, su curso y su pronóstico, se la considera una enfermedad heterogénea. En Colombia existen pocos registros que describan las características clínicas de los pacientes afectados por esta enfermedad. Métodos: Estudio descriptivo de corte transversal, se revisaron las historias clínicas de pacientes que consultaron a un hospital universitario en Colombia entre enero del 2004 y diciembre del 2019. Los registros se obtuvieron utilizando bases de datos de las unidades de dermatología, reumatología, dermatopatología, electrofisiología y códigos diagnósticos CIE10 asociados con dermatomiositis. Resultados: Se obtuvieron 70 pacientes con diagnóstico de dermatomiositis, 63 (90%) de los cuales cumplían criterios de clasificación de Bohan y Peter, en tanto que 7 (10%) presentaban dermatomiositis amiopática. El promedio de edad fue de 43 arios (DS ± 15,3); 48 fueron mujeres (68,5%); los signos clínicos más frecuentes fueron: pápulas de Gottron (80%, n = 56), eritema heliotropo (78,5%, n = 55) y poiquilodermia (75,7%, n = 53). Las manifestaciones sistêmicas más comúnmente encontradas fueron: disfagia (21,4%, n = 15), enfermedad pulmonar intersticial (11,4%, n = 8) e hipertensión pulmonar (8,5%, n = 6). Se documentó cáncer en el 8,5% (n = 6) de los pacientes. Conclusión: Se presenta información clínica de pacientes con dermatomiositis en un centro hospitalario de referencia en Colombia; los datos obtenidos concuerdan con la información de otros estudios de series de casos a escala mundial.

The effects of in ovo injection with sulfur amino acids and folic acid on the gene expression, relative organ weights, hematologic parameters, performance, and carcass characteristics of broiler chickens.

This study aimed to evaluate the effect of in ovo injection of folic acid (FA) and sulfur amino acids (SAAs) on the mitotic activity of myocytes, performance, relative organ weight, hematological values, and characteristics of broiler chicken carcasses. A total of 1200 fertile eggs from 42-week-old Ross AP© breeders were inoculated in the albumen on the first day of incubation in a completely randomized design with one of the treatments: C-intact eggs; SS: inoculation with 0.5 mL of saline solution; FA: 0.150 mg of FA; SAA: 5.90 mg of L-methionine and 3.40 mg of L-cysteine; or FA/SAA: FA + SAA. The inoculation of SAA did not influence (p > 0.05) the post-hatching characteristics of the chickens. FA inoculation increased (p < 0.05) the expression of the PAX7 and MYF genes in the pectoralis muscle of hatched chicks and reduced (p < 0.05) feed conversion at 42 days of age. The combination of SAA + FA increased (p < 0.05) the depth of the ileal crypt on the 1st day after hatching and the relative weight of the spleen and thymus on the 21st day of life. In conclusion, the inoculation of FA on the 1st day of incubation increases gene expression and improves the performance of broilers.

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey.

OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7). CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.

Fever in the initial stage of IIM patients: an early clinical warning sign for AE-ILD

Abstract Background Fever is a common symptom of Idiopathic inflammatory myopathies (IIM). However, the exact correlation between fever and the prognosis of IIM is still unclear. This study aims to clarify if the IIM patients initiated with fever are associated with poorer outcomes. Methods This was a single-center retrospective cohort study. Data were collected from 79 newly diagnosed, treatment-naive IIM patients in the Affiliated Wuxi People's Hospital of Nanjing Medical University (Wuxi, Jiangsu, China) from November 2016 to June 2020. According to the presence or absence of fever at the onset, the IIM patients were divided into two groups(fever group n = 28, without fever group n = 51) Clinical characteristics, laboratory data, treatment, and outcomes were recorded. The Kaplan-Meier and log-rank tests were used to compare the all-cause mortality, relapse rate, and acute exacerbation of interstitial lung disease (AE-ILD) incidence. The association of fever with the outcomes was assessed in the unadjusted and adjusted forward logistic regression model. Results Compared with the non-fever group, the age at onset of the fever group was higher, and mechanic's hands (MH) and interstitial lung disease (ILD) were more common. Systemic inflammation (CRP and ESR) was significantly higher in the fever group, while the level of albumin(ALB) and muscle enzymes were lower. The fever group seemed to be received more aggressive treatment, with higher dose glucocorticoids and higher rates of intravenous immunoglobulins(IVIG) use. The all-cause mortality rate and the incidence rate of AE-ILD were higher in the fever group. Even adjusted for the age at onset and treatments, fever was significantly associated with AE-ILD and all-cause mortality. Conclusion Our study has demonstrated that fever at initial diagnosis is associated with AE-ILD and mortality. Fever should serve as an early clinical warning sign for poor outcomes in IIM patients.

Intertubular morphometric and ultrastructural testes analyses in mdx mice.

Duchenne Muscular Dystrophy (DMD) reproductive alterations and the influence of antioxidant treatments may aid in understanding morphometry testicular quantification. In this context, the aim of the present study was to characterize the intertubular compartment (ITC) morphometry of animal testes in mdx mice supplemented with ascorbic acid (AA). Sixteen mice were used, namely the C57BL/10 (non-dystrophic) and C57BL/10Mdx (dystrophic) lineages, distributed into the following groups: Control (C60), Dystrophic (D60), Control supplemented with AA (CS60), Dystrophic supplemented with AA (DS60). A total of 200 mg/kg of AA were administered to mice for 30 days. Subsequently, the testicles were collected, weighed, and fragmented. The obtained fragments were fixed in Karnovsky's solution (pH 7.2) and embedded in historesin for morphometric and transmission electron microscopy assessments. Leydig cells were hypertrophic in the D60 group, but was reverted by AA supplementation in the DS60 group. The DS60 group also exhibited increased intertubular volume compared to the CS60 group. The ultrastructural images identified multilamellar bodies in dystrophic animals (lipid storage) and telocyte cells (transport substances) in both control and dystrophic animals. Morphometric alterations were, therefore, noted in the intertubular compartment due to Duchenne muscular dystrophy (DMD), with AA administration capable of altering Leydig cells in this condition.

Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.

Profile of specific and associated autoantibodies in patients with idiopathic inflammatory myopathies in a Colombian population.

Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune diseases with several forms of presentation. Diagnosis is mostly clinical in our region. Our aim was to evaluate the autoantibody profile of patients with IIMs. Methods: This study is a cross-sectional study with a prospective recollection of data, conducted between 2019-2021, in a single center in Cali, Colombia. Patients with a clinical diagnosis or suspicion of IIM were included. The presence of myositis-specific/associated antibodies was evaluated by immunoblotting in serum samples. Phenotypic characterization was performed. Results: A total of 36 patients were included. The mean age was 50.6 (16.7) years, and 20 (55.6%) were female. Eighteen (50%) patients were seropositive, of which 11 (30.5%) presented one positive antibody, with anti-TIF1É£being the most frequent (n = 4, 11.1%), followed by anti-Ro52 (n = 2, 5.6%). Seven patients (19.4%) showed >1 positive antibody. Dermatomyositis was the most frequent type of IIM in seropositive patients (n = 8, 44.4%), followed by anti-synthetase syndrome (n = 4, 22.2%). Weakness was symmetric and presented in the upper and lower extremities in 11 (61.1%) patients each. Both respiratory insufficiency and weight loss were seen in 7 (38.9%) patients, Gottron papules in six (33.3%) patients, and heliotrope rash, esophageal dysmotility, and myalgia in 5 (27.8%) patients. Pulmonary interstitial disease was seen in 4 (22.2%, with antibodies for anti-Ro52, anti-MDA5 + anti-Jo1 + anti-TIF1É£, anti-MDA5 + anti-SAE1 + anti-NXP2, and anti-cN1A + anti-Ro52) patients, and malignancy was seen in 2 (11.1%) patients (1 with anti-Mi2ß and 1 with anti-TIF1É£ + anti-Mi2α). In all, 7 (19.4%) patients required intensive care (2 seropositive, 1 with anti-PL7, 1 with anti-MDA5 + anti-Jo1 + anti-TIF1É£), and 1 (2.8%) (seronegative) patient died. Conclusion: This study is the first study in the Southwest of Colombia that evaluates myositis-specific/associated antibodies in IIM. Half of the patients were seropositive. Anti-TIF1É£was the most frequent MSA and anti-Ro52 was the most frequent MAA. Several patients presented antibody combinations. Further studies are needed to fully associate phenotypes with antibodies.

Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population.

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with limb-girdle muscle weakness of unknown etiology. Eighty-two patients were explored using high-throughput sequencing approaches with neuromuscular gene panels, establishing a definite genetic diagnosis in 49 patients (59.8%) and a highly probable genetic diagnosis in eight additional cases (9.8%). The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). The remaining 17 causative genes were present in one or two cases only. Twelve novel variants were identified. Five patients (6.1%) carried a variant of uncertain significance in genes partially matching the clinical phenotype. Twenty patients (24.4%) did not carry a pathogenic or likely pathogenic variant in the phenotypically related genes, including five patients (6.1%) presenting an autoimmune neuromuscular disorder. The relative frequency of the different forms of myopathy in Chile is like that of other series reported from different regions of the world with perhaps a relatively higher incidence of dysferlinopathy.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies.

OBJECTIVE: Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. METHODS: Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. RESULTS: The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. CONCLUSION: The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.

Inflammatory myopathies overlapping with systemic sclerosis: a systematic review.

We performed a systematic review of the clinical manifestations and complementary exams of patients with myopathies and systemic sclerosis overlap syndrome (MyoSScOS). Systematic review from January 1976 to November 2021 according PRISMA protocol on three electronic databases: PubMed, Web of Science, and Scopus. Studies were analyzed based on the following eligibility criteria: at least one combination of the terms described in the search strategy appears in the title; written in English, Portuguese, or Spanish; and addresses MyoSScOS. Brief communications, reviews, studies that addressed myopathies in children, congress proceedings, monographs, and dissertations were excluded. Thirty-five articles were selected. MyoSScOS seems to be more common in women. It also commonly affects the esophagus and joints with symmetrical and bilateral muscle involvement, Raynaud's phenomenon, and impairment of forced vital capacity. Concerning SSc, the most common subtype was the diffuse form. Cardiovascular and pulmonary complications are an important cause of death. Anti-centromere, anti-PM/Scl, anti-Scl70, anti-RNA polymerase III, anti-Ku, and anti-RNP were more correlated with this entity, and muscle biopsies may present a more aggressive pattern. Electroneuromyography patterns are quite similar to those found in inflammatory myopathies. The absence of studies with robust methodologies and the large number of case reports and series make more robust statistical analyses such as meta-analyses unfeasible. The characterization of MyoSScOS is important for the formulation of therapeutic measures and specific treatments aiming at better quality of life and prognosis. Greater and better theoretical contributions are necessary to better characterize it.