El paper dels anticossos a les miopaties

Les malalties autoimmunes són aquelles en les que es produeix una agressió incontrolada de les nostres pròpies estructures degut a un error del sistema immunològic que les reconeix com a estranyes. Existeix un debat a la comunitat mèdica sobre si els autoanticossos que apareixen a les malalties autoimmunes juguen un autèntic paper lesiu o són merament marcadors diagnòstics de determinades malalties. En aquest estudi s'analitza la freqüència dels diferents autoanticossos que apareixen en una de les malalties autoimmunes més rares, les miositis o miopaties inflamatòries.Las enfermedades autoinmunes son aquellas en las que se produce una agresión incontrolada de nuestras propias estructuras debido a un error del sistema inmunológico que las reconoce como extrañas. Existe un debate en la comunidad médica sobre si los autoanticuerpos que aparecen en las enfermedades autoinmunes desempeñan un auténtico papel lesivo o son meramente marcadores diagnósticos de determinadas enfermedades. En este estudio se analiza la frecuencia de los diferentes autoanticuerpos que aparecen en una de las enfermedades autoinmunes más raras, las miositis o miopatías inflamatorias

Miopaties i intolerància al gluten

Les miopaties inflamatòries són malalties de caràcter immunològic que presenten un infiltrat inflamatori en el teixit muscular. La causa encara no es coneix prou bé, però es creu que es tracta d'una resposta immunològica anormal del nostre organisme. Com que s'han descrit casos puntuals en els quals la malaltia celíaca acompanya la miopatia, investigadors de la UAB estan estudiant la possible relació entre aquestes malalties i la intolerància al gluten.Las miopatías inflamatorias son enfermedades de naturaleza inmunológica. La causa no se conoce bien, pero se cree que se trata de una respuesta inmunológica anormal de nuestro organismo. Como se han descrito casos puntuales en los que la enfermedad celíaca acompaña a la miopatía, investigadores de la UAB están estudiando la posible relación entre estas enfermedades y la intolerancia al gluten.Inflammatory myopathies are immunological diseases that cause inflammation in the muscular tissue. The cause and mechanisms of these diseases are not yet right known. Their origin could be an unusual immunological answer of human organism. Sometimes, myopathy appears at the same time that celiac disease. UAB researchers are studying a possible connection between myopathies and gluten intolerance

Role of autoantibodies in the diagnosis and prognosis of interstitial lung disease in autoimmune rheumatic disorders

Autoanticuerpos; Trastornos reumáticos autoinmunes; Enfermedad pulmonar intersticialAutoanticossos; Trastorns reumàtics autoimmunes; Malaltia pulmonar intersticialAutoantibodies; Autoimmune rheumatic disorders; Interstitial lung diseaseInterstitial lung disease (ILD) has been recognized as a frequent manifestation associated with a substantial morbidity and mortality burden in patients with autoimmune rheumatic disorders. Serum autoantibodies are considered good biomarkers for identifying several subsets or specific phenotypes of ILD involvement in these patients. This review features the role of several autoantibodies as a diagnostic and prognostic biomarker linked to the presence ILD and specific ILD phenotypes in autoimmune rheumatic disorders. The case of the diverse antisynthetase antibodies in the antisynthease syndrome or the anti-melanoma differentiation-associated 5 protein (MDA5) antibodies as a marker of a severe condition such as rapidly progressive ILD in patients with clinically amyopathic dermatomyositis are some of the associations herein reported in the group of myositis spectrum disorders. Specific autoantibodies such as the well-known anti-topoisomerase I (anti-Scl70) or the anti-Th/To, anti-U11/U12 ribonucleoprotein, and anti-eukaryotic initiation factor 2B (eIF2B) antibodies seems to be specifically linked to ILD in patients with systemic sclerosis. Overlap syndromes between systemic sclerosis and myositis, also have good ILD biomarkers, which are the anti-PM/Scl and anti-Ku autoantibodies. Lastly, other not so often reported disorders as being associated with ILD but recently most recognized as is the case of rheumatoid arthritis associated ILD or entities herein included in the miscellaneous disorders section, which include anti-neutrophil cytoplasmic antibody-associated interstitial lung disease, Sjögren’s syndrome or the mixed connective tissue disease, are also discussed.The authors received no financial support for the research, authorship, and/or publication of this article

L'Envelliment, aproximació a un procés complex i heterogeni

L'envelliment és un procés complex i heterogeni, no tots envellim de la mateixa manera. En els últims anys s'han incorporat nous conceptes clínics i biològics que poden arribar a qüestionar la natura fisiològica del procés. En aquest capítol es defineix el procés i la seva repercussió en la nostra societat, s'incorporen conceptes com ara la fragilitat, la comorbiditat o la discapacitat, que permeten entendre millor i més bé les repercussions de l'envelliment sobre el nostre organisme, i s'analitzen les peculiaritats dels que envelleixen de manera satisfactòria i arriben a centenaris. Es discuteix el concepte anti-aging des d'una vessant científica i analitzant altres connotacions del concepte. Finalment, s'intenta relacionar l'envelliment del sistema immunitari (immunosenescència) amb algunes malalties autoimmunitàries sistèmiques com ara l'esclerodèrmia i l'arteritis de cèŀlules gegants, i es comenta la progèria i les síndromes progeroides com a models d'estudi de l'envelliment.Aging is a complex and heterogeneous process, with relevant differences between subjects. Conceptual, clinic and biological concepts which can challenge the physiologic nature of aging have been incorporated during the last years. In this chapter a proper definition of aging and the social repercussion of the phenomenon is established, and new concepts such as fragility, comorbidity and discapacity which allow a better understanding of aging and related pathology are described. Centenarians and its rationale is also discussed and analyzed, along with the anti-aging phenomenon and its repercussions on agining. Lastly, a possible relationship between some autoimmune systemic diseases such as systemic sclerosis and giant cell vasculitis (Horton’s disease) and immunosenescence, and also the progeroid syndromes as a model of aging are addressed

COVID-19 Vaccination in Autoimmune Diseases (COVAD) study: Vaccine safety in idiopathic inflammatory myopathies

COVID-19; Dermatomyositis; VaccinationCOVID-19; Dermatomiositis; VacunaciónCOVID-19; Dermatomiositis; VacunacióIntroduction/Aims In this study we investigated COVID-19 vaccination–related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs). Methods Seven-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics were obtained and multivariable regression was performed. Results Ten thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30-455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04-7.3) and minor (OR, 1.5; IQR, 1.1-2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2-4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1-3.3; and OR, 2.2; IQR, 1.1-4.3, respectively). Overall, ADEs were less frequent in inclusion-body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients. Discussion Seven-day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs. Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines.National Institution for Health Research Manchester Biomedical Research Centre (to H.C.)

Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation

Idiopathic inflammatory myopathies; GenomeMiopatías inflamatorias idiopáticas; GenomaMiopaties inflamatòries idiopàtiques; GenomaObjective The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine-map associations and identify novel associations in IIM. Methods We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups. Results The HLA locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. Conclusion We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.Supported by the Intramural Research Program, National Institute of Environmental Health Sciences, NIH. Dr. Lundberg's work was supported by grants from the Swedish Research Council and Stockholm Regional Council (ALF). Dr. Vencovsky's work was supported by the Czech Ministry of Health–Conceptual Development of Research Organization (award 00023728) (Institute of Rheumatology). Drs. Hanna and Machado's work were supported by the NIHR University College London Hospitals Biomedical Research Centre. Drs. De Bleecker and De Paepe's work were supported by the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD). Dr. Wedderburn's work was supported by Versus Arthritis (awards 21593 and 21552), the Wellcome trust (award 085860), Myositis UK, the Cure JM Foundation, the Remission Charity, and the NIHR Biomedical research Centre at GOSH. Dr. Chinoy's work was supported by the Medical Research Council UK (award MR/N003322/1), Myositis UK, and the NIHR Manchester Biomedical Research Centre Funding Scheme. Dr. Lamb's work was supported by the Medical Research Council UK (award MR/N003322/1) and Myositis UK

COVID-19 Vaccination In Autoimmune Diseases (COVAD) Study: Vaccine Safety In Idiopathic Inflammatory Myopathies

INTRODUCTION/AIMS: We studied COVID-19 vaccination-related adverse events (ADEs) 7-days post-vaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs). METHODS: 7-day vaccine ADEs were collected in an international patient self-reported e-survey. Descriptive statistics and multivariable regression were performed. RESULTS: 10,900 respondents [1227 IIMs; 4640 SAIDs; 5033 healthy controls (HCs), median age 42 (IQR 30-55) years, 74% female, 45% Caucasian, 69% completely vaccinated] were analysed. 76.3% IIMs patients reported minor and 4.6% major ADEs. Patients with active IIMs reported more frequent major [OR 2.7 (1.04-7.3)] and minor [OR 1.5 (1.1-2.2)] ADEs than inactive IIMs. Rashes were more frequent in IIMs [OR-2.3(1.2-4.2)] than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs [OR 1.9 (1.1-3.3), OR 2.2 (1.1-4.3)]. Overall, ADEs were less frequent in inclusion body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients DISCUSSION: 7-day post-vaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rashes in IIMs. Patients with DM, active disease may be at higher risk, and IBM patients at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID-19 through vaccination likely outweighs the risk of vaccine-related ADEs Our results may inform future guidelines regarding COVID-19 vaccination in patients with SAIDs, and specifically in IIMs. Studies to evaluate long-term outcomes and disease flares are needed to shed more light on developing future COVID-19 vaccination guidelines

COVAD survey 2 long-term outcomes: unmet need and protocol

COVID-19; Registries; VaccinationCOVID-19; Registros; VacunaciónCOVID-19; Registres; VacunacióVaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups.HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study

Myositis; Pain; Rheumatic diseasesMiositis; Dolor; Enfermedades reumáticasMiositis; Dolor; Malalties reumàtiquesObjectives To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). Methods Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. Results Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0–5.0), 3.0 (IQR = 1.0–6.0), and 1.0 (IQR = 0–2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5–4.5, and NRS = 3.6, 95% CI = 3.1–4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. Conclusion Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme