anti-U1RNP Antibodies Research Articles

Autoantibodies Affect Brain Density Reduction in Nonneuropsychiatric Systemic Lupus Erythematosus Patients.

This study explores the relationship between autoantibodies and brain density reduction in SLE patients without major neuropsychiatric manifestation (NPSLE). Ninety-five NPSLE patients without obvious cerebral deficits, as determined by conventional MRI, as well as 89 control subjects, underwent high-resolution structural MRI. Whole-brain density of grey matter (GMD) and white matter (WMD) were calculated for each individual, and correlations between the brain density, symptom severity, immunosuppressive agent (ISA), and autoantibody levels were assessed. The GMD and WMD of the SLE group decreased compared to controls. GMD was negatively associated with SLE activity. The WMD of patients who received ISA treatment were higher than that in the patients who did not. The WMD of patients with anticardiolipin (ACL) or anti-SSB/La antibodies was lower than in patients without these antibodies, while the GMD was lower in patients with anti-SM or anti-U1RNP antibodies. Thus, obvious brain atrophy can occur very early even before the development of significant symptoms and specific autoantibodies might contribute to the reduction of GMD or WMD in NPSLE patients. However, ISAs showed protective effects in minimizing GMD and WMD reduction. The presence of these specific autoantibodies might help identify early brain damage in NPSLE patients.

Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus.

IntroductionNeuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies revealed the strong association between serum anti-Sm and organic brain syndrome, consisting mainly of acute confusional state (ACS) of diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). However, the precise mechanism by which anti-Sm causes diffuse NPSLE remains unclear. Of note, recent studies demonstrated that anti-U1 RNP antibodies (anti-RNP) in cerebrospinal fluid (CSF) are associated with NPSLE. The present study was designed to explore the association of anti-Sm antibodies in CSF with NPSLE.MethodsPaired serum and CSF specimens were obtained from 72 patients with NPSLE (49 with diffuse NPSLE, 23 with neurological syndromes or peripheral neuropathy (focal NPSLE) and from 22 control patients with non-SLE neurological diseases. Sera were also obtained from 41 patients with active SLE without neuropsychiatric manifestations (non-NPSLE). Anti-Sm and anti-RNP were measured by enzyme-linked immunosorbent assay (ELISA). Blood-brain barrier (BBB) function and intrathecal anti-Sm production were evaluated by Q albumin and CSF anti-Sm index, respectively. Binding of anti-Sm to neuroblastoma cell lines SK-N-MC and Neuro2a was examined by flow cytometry and by cell ELISA.ResultsAnti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE control. CSF anti-Sm, but not CSF anti-RNP, was significantly elevated in ACS compared with non-ACS diffuse NPSLE or with focal NPSLE. By contrast, there were no significant differences in serum anti-Sm or anti-RNP among subsets of NPSLE and non-NPSLE. Whereas there were no significant differences in CSF anti-Sm index, Q albumin was elevated in ACS compared with non-ACS or with focal NPSLE. Notably, CSF anti-Sm was correlated with Q albumin (r = 0.2373, P = 0.0447) or with serum anti-Sm (r = 0.7185, P <0.0001) in 72 patients with NPSLE. Finally, monoclonal anti-Sm and purified human anti-Sm bound to the surface of SK-N-MC and Neuro2a.ConclusionsThese results demonstrate that the elevation of CSF anti-Sm through transudation from systemic circulation due to damaged BBB plays a critical role in the pathogenesis of ACS. More importantly, the data indicate that anti-Sm is yet another autoantibody with presumed neural toxicity, but might not be the last.

Pericardial tamponade and pancytopenia as the first manifestation of mixed connective tissue disorder and its complete reversal with corticosteroids

We report a case of a 25-year-old lady who presented to our department with complaints of easy fatigability and shortness of breath since one week. She had a history of Raynaud’s phenomenon. Examination revealed scleroderma like skin changes and pericardial friction rub. Investigations revealed high titer of anti-U1 RNP antibodies along with co-existing pancytopenia. Chest x-ray and echocardiography confirmed pericardial tamponade. Patient was diagnosed as having mixed connective tissue disorder (MCTD) and she was started on high dose prednisolone, which led to complete reversal of pancytopenia and pericardial tamponade after 1 month of treatment. There are only 6 reported cases of pericardial tamponade in a patient with MCTD, and none of them had pancytopenia. Present case highlights the need to investigate the patient of pericardial tamponade for MCTD, especially in the presence of pancytopenia and relevant clinical history, as prompt treatment with corticosteroids can avoid invasive procedures like pericardiocentesis.

OP0215 Association of Cerebrospinal Fluid Anti-Sm Antibodies with Acute Confusional State in Systemic Lupus Erythematosus

BackgroundNeuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies disclosed the strong association between serum anti-Sm antibodies and organic brain...

AB0960 Autoantibodies to Heat-Shock Protein60 and Cardiovascular Disease in Patients with Mixed Connective Tissue Disease

BackgroundHeat Shock Proteis (HSP) are intracellular proteins conserved in the course of evolution. Resulting from the antigenic homology of various species, HSP60 and antibodies produced against them can provoke inflammation....

Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran-Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31-0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37-0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13-0.62 for heterozygotes and OR 0.11, 95 % CI 0.03-0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.

Association between anti-U1 ribonucleoprotein antibodies and inflammatory mediators in cerebrospinal fluid of patients with neuropsychiatric systemic lupus erythematosus

We investigated possible associations between neurotoxic inflammatory mediators (IMs) and anti-U1RNP antibodies (Abs) in cerebrospinal fluid (CSF) of neuropsychiatric systemic lupus erythematosus (NPSLE). Serum and CSF anti-U1RNP Abs were detected using an RNA-immunoprecipitation assay and CSF anti-U1RNP Ab levels were measured by ELISA. IFN-α, MCP-1 and IL-8 levels in CSF were determined by quantitative multiplex cytokine analysis. IM levels were compared among anti-U1RNP-positive and anti-U1RNP-negative NPSLE as well as other rheumatic disease controls (controls). Anti-U1RNP Abs were detected in serum (58%) and in CSF (18%) of 82 NPSLE patients. CSF MCP-1 levels were higher in NPSLE than in controls. CSF IFN-α level was higher in CSF anti-U1RNP Ab-positive than in -negative patients or controls. When limited to serum anti-U1RNP Ab-positive patients, however, levels of all three IMs in CSF were higher in CSF anti-U1RNP Ab-positive than in -negative patients. Anti-U1RNP Ab levels in CSF correlated with CSF MCP-1, but not IFN-α and IL-8 levels. CSF anti-U1RNP Ab positivity is associated with increased level of CSF IFN-α. MCP-1 levels correlated with CSF anti-U1RNP Ab levels, whereas the increased CSF MCP-1 was not specific to CSF anti-U1RNP Ab-positive NPSLE.

Distinct antibody profile: a clue to primary antiphospholipid syndrome evolving into systemic lupus erythematosus?

We have performed a retrospective study to determine if patients with antiphospholipid syndrome that developed systemic lupus erythematosus (APS/SLE) had distinct clinical and/or serological features. All 80 primary APS (PAPS) patients followed up at our APS unit were included in the study and divided into two groups: 14 APS/SLE and 66 PAPS. Prior or at onset of lupus manifestations, six patients were uniformly negative for lupus and Sjögren autoantibodies, and the other eight patients had persistent positive. In the first year after diagnosis of SLE, three patients remained with negative antibodies, the other seven patients maintained the same antibodies, and four patients developed other antibodies. APS/SLE group had a significant lower mean age at PAPS diagnosis (26.0 ± 8.0 vs. 34.2 ± 11.9 years, p = 0.03) and a longer disease duration (14.0 ± 7.0 vs. 6.0 ± 5.0 years, p < 0.0001). The mean time for PAPS to develop SLE was 5.2 ± 4.3 years. The typical clinical and laboratorial findings of APS did not discriminate both groups of patients. At lupus onset, antinuclear antibodies were more frequently observed in those who evolved to SLE (100 vs. 51.5%, p = 0.0005). Anti-double-stranded DNA (dsDNA), anti-ribosomal P, anti-Ro/SS-A, anti-La/SS-B, and anti-U1RNP antibodies were exclusively found in the APS/SLE patients, whereas anti-Smith (Sm) antibodies were not detected in both groups. The detection of a distinct subgroup of lupus-associated autoantibody in PAPS patients seems to be a hint to overt SLE disease, particularly in those patients with young age at diagnosis.

AB0502 Long-term follow-up of esophageal diameter in patients with anti-centromere antibody sero-positive systemic sclerosis and primary sjögren’s syndrome

BackgroundAnti-centromere antibodies (ACA) are characteristic autoantibodies which are detected in patients with systemic sclerosis (SSc) and primary Sjögren’s syndrome (pSS). We previously reported that ACA are a useful marker of...

AB0805 Nailfold capillaroscopy findings are different between patients with U1RNP antibody and systemic sclerosis or patients with systemic lupus erythematosus and U1RNP antibody

BackgroundNailfold capillaroscopy (NC) is the best tool to study microcirculation in patients with Raynaud’s phenomenon (RF) or patients with connective tissue diseases. There are some characteristic capillaroscopy findings in systemic...

Correlation of interferon‐inducible chemokine plasma levels with disease severity in systemic sclerosis

To measure interferon (IFN)-inducible chemokines in the plasma of patients with systemic sclerosis (SSc) and investigate whether the chemokine levels are correlated with disease severity. Plasma levels of the IFN-inducible chemokines IFNγ-inducible protein 10 (IP-10/CXCL10), IFN-inducible T cell α chemoattractant (I-TAC/CXCL11), and monocyte chemoattractant protein 1 (CCL2) were measured in SSc patients and examined for correlation with the IFN gene expression signature. A composite IFN-inducible chemokine score was generated for chemokines showing a correlation with the IFN gene signature (IP-10 and I-TAC), and this score was compared between 266 patients with SSc enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 97 matched control subjects. Subsequently, the correlation between the IFN-inducible chemokine score at baseline and markers of disease severity was assessed. In addition, the course of the IFN-inducible chemokine score over time was examined. The plasma IFN-inducible chemokine score correlated with the IFN gene expression signature, and this score was higher in SSc patients compared to controls. The IFN-inducible chemokine score was also associated with the absence of anti-RNA polymerase III antibodies and presence of anti-U1 RNP antibodies, but not with disease duration, disease type, or other autoantibodies. The chemokine score correlated with concomitantly obtained scores on the Medsger Severity Index for muscle, skin, and lung involvement in SSc, as well as the forced vital capacity, diffusing capacity for carbon monoxide, and creatine kinase levels. The association of the chemokine score with disease severity was independent of the presence of anti-U1 RNP or other potential confounders (age, sex, ethnicity, disease duration, and treatment with immunosuppressive agents). Finally, there was not a significant change in the IFN-inducible chemokine score over time. The IFN-inducible chemokine score is a stable serologic marker of a more severe form of SSc and may be useful for risk stratification of patients, regardless of disease type (limited or diffuse) or duration of disease.

Child‐onset systemic sclerosis positive for anticentromere antibodies: Two Japanese cases

Systemic sclerosis (SSc) is an uncommon connective tissue disease of childhood. Moreover, pediatric SSc positive for anticentromere antibodies (ACA) is extremely rare. We describe two cases of ACA-positive SSc in Japanese girls with clinical findings. Case 1 is a 15-year-old female. From disease onset at 7 years, she developed limited cutaneous (no internal involvement) SSc positive for ACA and anti-U1RNP antibodies, but negative for antitopoisomerase I antibodies (ATA). She also showed calcinosis, sclerodactyly, and telangiectasia, but not Raynaud's phenomenon. Case 2 is also a 15-year-old female with onset at the same age. Her diagnosis was limited cutaneous SSc positive for ACA, anti-SSA/Ro antibodies, and anti-thyroid antibodies, but not ATA. She showed sclerodactyly, telangiectasia, and Raynaud phenomenon, as well as complicated Sjögren's syndrome and chronic thyroiditis with euthyroidism. We reported that two Japanese girls with SSc were positive for ACA and other antibodies with the exception of ATA.

Clinical characteristics and survival of Japanese patients with connective tissue disease and pulmonary arterial hypertension: a single-centre cohort

To clarify the characteristics, survival and predictors of mortality in Japanese patients with pulmonary arterial hypertension (PAH) associated with CTD. This single-centre cohort study enrolled 70 consecutive patients with PAH-CTD who visited a tertiary referral centre in Japan between 1970 and 1990 (n=30, historical group) and between 2000 and 2009 (n=40, recent group). Baseline clinical features, haemodynamic parameters and ANA profiles were recorded. The Cox proportional hazards regression model was used to determine independent factors associated with an increased risk of mortality. MCTD and SLE were the major underlying CTDs, comprising 43% and 29% of PAH patients respectively, whereas SSc was less common (19%). Anti-U1RNP antibody was the most prevalent ANA (61%). The cumulative survival rate was significantly better in the recent group in comparison with the historical group (76% vs 26% at 3 years; P<0.001). When both groups were combined, World Health Organization functional class III or IV at diagnosis was identified as an independent predictor of mortality, whereas modern PAH drug use was associated with a favourable outcome. The major PAH-CTD population in Japan suffers from MCTD or SLE with anti-U1RNP antibody, in contrast to PAH-CTD patients in the USA and Europe. Modern PAH treatment has improved survival rates, but long-term outcomes are still unsatisfactory. Independent predictors of mortality indicate that early diagnosis and the prompt use of PAH drugs should improve survival.

Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Current Status and Future Direction

Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue diseases (CTDs) including systemic sclerosis and systemic lupus erythematosus (SLE). The prevalence of PAH in SLE is estimated to be 0.5% to 17.5%. The pathophysiology of PAH involves multiple mechanisms from vasculitis and in-situ thrombosis to interstitial pulmonary fibrosis which increases pulmonary vascular resistance, potentially leading to right heart failure. Immune and inflammatory mechanisms may play a significant role in the pathogenesis or progression of PAH in patients with CTDs, establishing a role for anti-inflammatory and immunosuppressive therapies. The leading predictors of PAH in SLE are Raynaud phenomenon, anti-U1RNP antibody, and anticardiolipin antibody positivity. The first-line of diagnostic testing for patients with suspected SLE-associated PAH (SLE-aPAH) involves obtaining a Doppler echocardiogram. Once the diagnosis is confirmed by right heart catheterization, SLE-aPAH patients are generally treated with oxygen, anticoagulants, and vasodilators. Although the prognosis and therapeutic responsiveness of these patients have improved with the addition of intensive immunosuppressive therapies, these treatments are still largely unproven. Recent data put the one-year survival rate for SLE-aPAH patients at 94%. Pregnant women are most at risk of dying due to undiagnosed SLE-aPAH, and screening should be considered essential in this population.

Rapidly Progressive Respiratory Failure in Mixed Connective Tissue Disease: Report of an Autopsy Case

A 64-year-old woman presented with exertional dyspnea. The case was diagnosed as mixed connective tissue disease (MCTD) due to presence of swollen fingers, Raynaud's phenomenon, muscle weakness, positive anti-U1RNP antibody, pericarditis and interstitial pneumonia. Although the histology from a transbronchial lung biopsy (TBLB) indicated organizing pneumonia, corticosteroid therapy was postponed for two months at the patient's request. She died 8 weeks later from acute progressive interstitial pneumonia in spite of the administration of intravenous cyclophosphamide combined with prednisolone. The autopsy revealed exudative and organizing diffuse alveolar damage (DAD). Previous reports have shown that DAD is an extremely rare pulmonary complication in MCTD. This report presents a case of MCTD with acute respiratory failure. This case thus suggests that this therapy should be administered as soon as possible.

Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with systemic lupus erythematosus: two cases without features of scleroderma

Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)-SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone (p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter (p < 0.05). Although anti-RNAP III is highly specific for SSc, cases with coexisting anti-U1RNP are not so uncommon among anti-RNAP III positives (8%, 3/35) and may be SLE without features of SSc.

Survival in scleroderma: results from the population‐based South Australian Register

To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). The SASR is a population-based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15-year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n = 786). Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28-1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti-topoisomerase (Scl-70) and anti-U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5-75.7), diffuse scleroderma 62.9 years (95% CI 59.4-66.4) and overlap disease 57.8 years (95% CI 48.7-66.9). Survival improved over the 15-year study period. Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma-associated antibodies, Scl-70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15-year study period.

Anti–U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease

To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE). The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. The frequency of anti-U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti-U1 RNP index ([CSF anti-U1 RNP antibodies/serum anti-U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin-6 (IL-6) levels and the albumin quotient (Qalb, an indicator of blood-brain barrier damage). CSF and serum antibodies against U1-70K, U1-A, and U1-C, including autoantigenic regions, were examined, and the U1-70K, U1-A, and U1-C indices as well as the anti-U1 RNP index were calculated. CSF anti-U1 RNP antibodies with an increased anti-U1 RNP index showed 64.3% sensitivity and 92.9% specificity for central NPSLE. The anti-U1 RNP index did not correlate with CSF IL-6 levels or the Qalb. The anti-U1-70K index was higher than the anti-U1-A and anti-U1-C indices in the CSF of anti-U1 RNP antibody-positive patients with central NPSLE. The major autoantigenic region for CSF anti-U1-70K antibodies appeared to be localized in U1-70K amino acid 141-164 residue within the RNA-binding domain. The frequency of anti-U1 RNP antibodies in the CSF and the anti-U1 RNP index are useful indicators of central NPSLE in anti-U1 RNP antibody-positive patients. The predominance of anti-U1-70K antibodies in CSF suggests intrathecal anti-U1 RNP antibody production.

Pulmonary arterial hypertension related to connective tissue diseases

Pulmonary arterial hypertension (PAH) is an important complication of connective tissue diseases (CTD) and especially seen in systemic sclerosis, systemic lupus erythematosis (SLE), and mixed connective tissue disease (MCTD). In systemic sclerosis, PAH is isolated or accompanied by interstitial lung disease and currently, a major cause of mortality. It has been shown to be developed in approximately 10% of cases and annual screening with echocardiography has been recommended. Right heart catheterization is required for definite diagnosis. Limited skin involvement, late onset, Raynaud's phenomenon, digital ulcers, telangiectasias, diminished nail fold capillaries, anti-U3RNP and anticentromere antibodies are known as risk factors for PAH development in systemic sclerosis. Following diffusion lung capacity for carbon monoxide (DLCO) and pro-brain natriuretic peptide (pro-BNP) levels can be helpful for evaluating PAH development. PAH in SLE linked to antiphospholipid antibodies and Raynaud's phenomenon in some studies. MCTD is an overlap syndrome with features of systemic sclerosis, SLE, polymyositis and positive anti-U1RNP antibodies. PAH develops in 9-27% of the patients and the leading cause of mortality in patients with MCTD. Endothelin receptor antagonists, prostacyclin analogs and phosphodiesterase 5 inhibitors are being used in patients with systemic sclerosis. In SLE/MCTD patients with early diagnosis immunosuppressive treatments may be effective.

Severe and refractory myositis in mixed connective tissue disease: a description of a rare case

Mixed connective tissue disease (MCTD) is a rare disease that includes clinical and laboratorial manifestations of systemic lupus erythematosus, scleroderma and polymyositis that is associated with high titers of anti-U1RNP antibodies. In general, muscle involvement is subclinical, usually appearing as an increase in muscle enzyme levels that tends to be a characteristic of the initial phases of the disease. Severe clinical muscle weakness is not observed in this disease. The objective of this study is to report a rare case of a patient who presented a severe onset of myositis characterized by dysphagia, an increase in myopathy and a weakening of the cervical musculature. While there was no response to the administration of an initial dose of corticosteroids, improvement was observed after increasing the dose of corticosteroids, in addition to the initiation of pulse therapy with methylprednisolone accompanied by methotrexate treatment. The authors emphasize that there is only one previously reported case regarding a child with MCTD and severe clinical myopathy on electromyography and muscle biopsy, and they report in this article one adult female patient who presented severe myositis and was refractive to corticotherapy.