RESUMO
BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.
Assuntos
Autoanticorpos/imunologia , Dermatomiosite/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Miosite/fisiopatologia , Adulto , Idoso , Alanina-tRNA Ligase/imunologia , Anticorpos Antinucleares/imunologia , China , Estudos de Coortes , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Glucocorticoides/uso terapêutico , Glicina-tRNA Ligase/imunologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/fisiopatologia , Imunossupressores/uso terapêutico , Isoleucina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/imunologia , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Treonina-tRNA Ligase/imunologia , Resultado do Tratamento , Capacidade VitalRESUMO
BACKGROUND: Each myositis-specific autoantibody (MSA) tends to have a distinct clinical presentation. Coexistence of MSAs do not commonly occur. If they do, it is unknown if there is an overlap of clinical features or prognostic implications. There are a few reported cases of overlap between these antibodies, mostly reported in patients with Japanese descent. Our aim for this case report is to turn more attention and interest for future MSA profile studies in the Hispanic population, which may hopefully spur better therapies if we realize the prognostic implications of certain myositis subsets including double-positive autoantibody syndromes. CASE PRESENTATION: A 27-year-old Hispanic female was admitted to the medical intensive care unit due to acute hypoxemic respiratory failure secondary to acute respiratory distress syndrome (ARDS). She had failed conventional mechanical ventilation and was cannulated for venovenous extracorporeal membrane oxygenation (VV-ECMO) to manage her respiratory failure. She had erythematous scaly plaques on bilateral 3rd metacarpophalangeal joints on examination. Her autoimmune workup revealed positivity for both anti-PL-7(threonyl) and anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies. After extensive evaluation, it was concluded that she had rapidly progressive interstitial lung disease (RPILD) due to amyopathic dermatomyositis. Despite maximal medical management, she was ultimately transitioned to comfort care measures and expired. CONCLUSION: We would like to highlight the rarity of double antibody positive amyopathic dermatomyositis. This unique clinical presentation has only been reported in persons of Japanese descent. Our case is likely to be the first reported to occur in a person of Hispanic descent in the United States. The rarity of our case could stimulate further study of overlapping MSA to understand its varied presentations and prognoses including possible tendency toward a rapidly progressive ILD phenotype. Earlier detection of these clinical syndromes can lead to better outcomes for patients with RPILD. This case report could also herald an increased recognition and understanding of MSA profile in the Hispanic population in the USA.
Assuntos
Autoanticorpos/sangue , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Adulto , Dermatomiosite/complicações , Progressão da Doença , Feminino , Hispânico ou Latino , Humanos , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/imunologia , Prognóstico , Treonina-tRNA Ligase/imunologiaAssuntos
Insuficiência Cardíaca/imunologia , Hipertensão Pulmonar/imunologia , Miosite/complicações , Miosite/diagnóstico por imagem , Treonina-tRNA Ligase/imunologia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Pessoa de Meia-IdadeRESUMO
Anti-PL-7 is an anti-tRNA synthetase antibody, and interstitial lung disease (ILD) is the most frequent complication of anti-PL-7-associated antisynthetase syndrome. However, the features of ILD have not been fully elucidated. The present study retrospectively compares 7 and 15 patients who were positive for anti-PL-7 and anti-Jo-1 antibodies, respectively. The features of ILD did not significantly differ between the two groups, but the ratio of lymphocytes in bronchoalveolar lavage fluid was higher in the Jo-1 than in the PL-7 group. High-resolution computed tomography revealed nonspecific interstitial pneumonia in all patients in the PL-7 group and organizing pneumonia in four of the 15 patients in the Jo-1 group. These findings suggest that pulmonary complications slightly differ between patients expressing anti-PL-7 and anti-Jo-1 antibodies. Further studies are required to clarify the features of ILD associated with PL-7.
Assuntos
Anticorpos Antinucleares/sangue , Pneumonia em Organização Criptogênica/etiologia , Doenças Pulmonares Intersticiais/etiologia , Miosite/complicações , Treonina-tRNA Ligase/imunologia , Adulto , Biomarcadores/sangue , Pneumonia em Organização Criptogênica/sangue , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/imunologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/diagnóstico , Miosite/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios XAssuntos
Autoanticorpos/imunologia , Nefropatias/etiologia , Miosite/complicações , Treonina-tRNA Ligase/imunologia , Feminino , Humanos , Nefropatias/diagnóstico , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Esclerodermia Localizada/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
CASE PRESENTATION: A 64-year-old previously healthy man presented with 8 weeks of progressive dyspnea on exertion and cough. Prior to presentation, the patient was able to bicycle > 60 miles per week and work full-time in a home improvement store. He was up-to-date with age-appropriate cancer screening and immunizations, and home medications included famotidine for reflux and nonsteroidal antiinflammatories for osteoarthritis, both as-needed. He had no significant respiratory exposure, aside from previous work as an electrician. His symptoms began in mid-February 2020 amid the coronavirus disease 2019 pandemic, although he had no known exposure to the virus.
Assuntos
COVID-19/diagnóstico , Frutose-Bifosfato Aldolase/sangue , Glucocorticoides/administração & dosagem , Pulmão/diagnóstico por imagem , Miosite , Troca Plasmática/métodos , Rituximab/administração & dosagem , Treonina-tRNA Ligase/imunologia , Autoanticorpos/sangue , Diagnóstico Diferencial , Progressão da Doença , Humanos , Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Miosite/sangue , Miosite/diagnóstico , Miosite/fisiopatologia , Miosite/terapia , Oxigenoterapia/métodos , Prognóstico , Resultado do TratamentoRESUMO
An autoantibody known as PL-7 was found in the serum of four patients with myositis and one with a systemic lupus erythematosus-like syndrome. The PL-7 antigen is an 80,000 dalton polypeptide that coprecipitates with transfer RNA. In aminoacylation reactions, PL-7 IgG inhibited the charging of tRNA with threonine but had little or no effect on charging with other amino acids. Experimental antibodies raised against purified threonyl-tRNA synthetase recognized the same 80,000 dalton polypeptide, but tRNA was not coprecipitated. We conclude that PL-7 antibody is directed at threonyl-tRNA synthetase, and that different antigenic sites are recognized by the human and experimental autoantibodies. Our findings emphasize the link between myositis and autoimmunity to tRNA-related structures.
Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/análise , Miosite/imunologia , Treonina-tRNA Ligase/imunologia , Adulto , Animais , Especificidade de Anticorpos , Autoanticorpos/fisiologia , Autoantígenos/análise , Ligação Competitiva , Epitopos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Precipitina , RNA/análise , Coelhos , Treonina-tRNA Ligase/isolamento & purificaçãoAssuntos
Infecções Comunitárias Adquiridas/diagnóstico , Eosinófilos/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Neutrófilos/imunologia , Pneumonia/diagnóstico , Treonina-tRNA Ligase/imunologia , Adulto , Alanina Transaminase/sangue , Autoanticorpos/sangue , Proteína C-Reativa/metabolismo , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Metilprednisolona/administração & dosagem , Radiografia Torácica , SíndromeRESUMO
A 52-year-old man was admitted to our hospital for progressive dyspnea of 3 months duration and a skin rash of 4 months duration. Previously, he had been given a diagnosis of rheumatoid arthritis at age 40, then a diagnosis of interstitial pneumonia at age 46. Tacrolimus and prednisolone were begun at age 50, and 50 mg/week of etanercept was added 17 months before admission to our hospital. Due to renal dysfunction, tacrolimus was discontinued 9 months before admission. A skin rash developed 4 months before admission, and progressive dyspnea developed over the 3 months before admission. Tacrolimus was restarted at 1 mg/day and prednisolone was increased from 5 mg/day to 15 mg/day; however, neither the skin rash nor the dyspnea improved. After visiting a local physician, the patient was then referred to our institution. On presentation, skin changes such as erythema of the superior palpebrae and fingers were noted. His serum creatine phosphokinase level was elevated, but muscle strength was normal and no abnormal electromyographic and muscle biopsy findings were found. Anti-Jo-1 antibody was negative but anti PL-7 antibody was positive. The patient did not meet the diagnostic criteria of dermatomyositis/ polymyositis, so antisynthetase syndrome was diagnosed. Etanercept was discontinued and the prednisolone increased, which resulted in improvement of the interstitial pneumonia and skin rash. Antisynthetase syndrome should be considered as a differential diagnosis when skin rash and exacerbation of interstitial pneumonia are found during treatment for rheumatoid arthritis.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/sangue , Doenças Pulmonares Intersticiais/fisiopatologia , Treonina-tRNA Ligase/imunologia , Antirreumáticos/efeitos adversos , Etanercepte , Exantema/imunologia , Humanos , Imunoglobulina G/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral , SíndromeRESUMO
Threonyl-tRNA synthetase (TRS) is an aminoacyl-tRNA synthetase that catalyzes the aminoacylation of tRNA by transferring threonine. In addition to an essential role in translation, TRS was extracellularly detected in autoimmune diseases and also exhibited pro-angiogenetic activity. TRS is reported to be secreted into the extracellular space when vascular endothelial cells encounter tumor necrosis factor-α. As T helper (Th) type 1 response and IFN-γ levels are associated with autoimmunity and angiogenesis, in this study, we investigated the effects of TRS on dendritic cell (DC) activation and CD4 T cell polarization. TRS-treated DCs exhibited up-regulated expression of activation-related cell-surface molecules, including CD40, CD80, CD86, and MHC class II. Treatment of DCs with TRS resulted in a significant increase of IL-12 production. TRS triggered nuclear translocation of the NF-κB p65 subunit along with the degradation of IκB proteins and the phosphorylation of MAPKs in DCs. Additionally, MAPK inhibitors markedly recovered the degradation of IκB proteins and the increased IL-12 production in TRS-treated DCs, suggesting the involvement of MAPKs as the upstream regulators of NF-κB in TRS-induced DC maturation and activation. Importantly, TRS-stimulated DCs significantly increased the populations of IFN-γ+CD4 T cells, and the levels of IFN-γ when co-cultured with CD4+ T cells. The addition of a neutralizing anti-IL-12 mAb to the cell cultures of TRS-treated DCs and CD4+ T cells resulted in decreased IFN-γ production, indicating that TRS-stimulated DCs may enhance the Th1 response through DC-derived IL-12. Injection of OT-II mice with OVA-pulsed, TRS-treated DCs also enhanced Ag-specific Th1 responses in vivo. Importantly, injection with TRS-treated DC exhibited increased populations of IFN-γ+-CD4+ and -CD8+ T cells as well as secretion level of IFN-γ, resulting in viral clearance and increased survival periods in mice infected with influenza A virus (IAV), as the Th1 response is associated with the enhanced cellular immunity, including anti-viral activity. Taken together, these results indicate that TRS promotes the maturation and activation of DCs, DC-mediated Th1 responses, and anti-viral effect on IAV infection.
Assuntos
Células Dendríticas/imunologia , Vírus da Influenza A/fisiologia , Interleucina-12/metabolismo , NF-kappa B/metabolismo , Infecções por Orthomyxoviridae/imunologia , Células Th1/imunologia , Treonina-tRNA Ligase/metabolismo , Animais , Anticorpos Bloqueadores/metabolismo , Diferenciação Celular , Células Cultivadas , Feminino , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Treonina-tRNA Ligase/imunologiaRESUMO
OBJECTIVE: Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM. METHODS: Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations. RESULTS: Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013). CONCLUSION: Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.
Assuntos
Autoanticorpos/imunologia , Dermatomiosite/patologia , Músculo Quadríceps/patologia , Corticosteroides/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , DNA Topoisomerases/imunologia , Proteínas de Ligação a DNA/imunologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Estudos Longitudinais , Masculino , Metotrexato/uso terapêutico , Razão de Chances , Prognóstico , Fatores de Proteção , Fatores de Risco , Índice de Gravidade de Doença , Partícula de Reconhecimento de Sinal/imunologia , Treonina-tRNA Ligase/imunologia , Fatores de Transcrição/imunologia , Reino UnidoRESUMO
OBJECTIVE: The clinical and laboratory features of seven Japanese patients with anti-aminoacyl-tRNA synthetase (ARS) autoantibodies against PL-7 (anti-threonyl-tRNA synthetase) were analyzed and compared with previously published findings. METHODS: Serum samples from 1,135 Japanese patients with various autoimmune diseases were screened for anti-PL-7 antibodies using RNA and protein immunoprecipitation assays. The patients whose sera contained anti-PL-7 antibodies were assessed regarding clinical symptoms and clinical course. RESULTS: Sera from seven patients were found to have anti-PL-7 antibodies. These autoantibodies were associated with polymyositis/dermatomyositis (PM/DM) and/or interstitial lung disease (ILD). The clinical diagnoses of these seven patients were PM - systemic sclerosis (SSc) overlap (5 patients), DM (1 patient) and idiopathic pulmonary fibrosis (IPF) (1 patient). All patients had ILD with a chronic course and six also had arthritis (85%) and five sclerodactyly (71%). CONCLUSIONS: These results indicate that anti-PL-7 autoantibodies are closely associated with PM-SSc overlap as well as ILD, arthritis and sclerodactyly in our series of Japanese patients.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Treonina-tRNA Ligase/imunologia , Adulto , Povo Asiático , Doenças Autoimunes/etnologia , Dermatomiosite/etnologia , Dermatomiosite/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/etnologia , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Polimiosite/etnologia , Polimiosite/imunologia , Fibrose Pulmonar/etnologia , Fibrose Pulmonar/imunologia , Escleroderma Sistêmico/etnologia , Escleroderma Sistêmico/imunologiaAssuntos
Alanina-tRNA Ligase/imunologia , Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Dermatomiosite/diagnóstico , Histidina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Treonina-tRNA Ligase/imunologia , Biomarcadores/sangue , Western Blotting/métodos , Dermatomiosite/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunodifusão/métodos , Imunoprecipitação/métodos , Valores de Referência , Manejo de EspécimesRESUMO
INTRODUCTION: Interstitial lung disease can be idiopathic or occur in the setting of connective tissue diseases. In the latter case it requires a different treatment approach with a better prognosis. Interstitial lung disease can precede the onset of typical connective tissue disease features by many years, and therefore meticulous multidisciplinary follow-up is crucial. This case highlights the diagnostic challenge and the need for intensified attention for subtle clinical features when faced with interstitial lung disease in patients with characteristics of a hitherto undifferentiated connective tissue disease. CASE PRESENTATION: A 44-year-old Caucasian woman presented to our pulmonology department with dyspnea, Raynaud's phenomenon and subtle swelling of fingers and eyelids. Laboratory analysis and autoantibody screening was negative. She was diagnosed with nonspecific interstitial pneumonia with a concurring undifferentiated connective tissue disease. After four years of stable disease, she presented with rapid pulmonary deterioration, myalgia, periorbital edema, arthritis and a cracked appearance of the radial sides of the fingers of both her hands. This clinical sign was recognized as mechanic's hands and a specific search for the presence of antisynthetase antibodies was performed. She was found to harbor anti-threonyl-tRNA synthetase antibodies. A diagnosis of antisynthetase syndrome was made and she was treated with glucocorticoids and immunosuppressives. CONCLUSIONS: This case highlights the difficulty in fine-tuning the diagnosis when confronted with a patient with interstitial lung disease and the suspicion of an underlying, yet undifferentiated connective tissue disease. There is a strong need for clinical multidisciplinary follow-up of these patients, with a high level of alertness to rare and specific clinical signs. The diagnosis of the underlying connective tissue disease profoundly influences the management of the interstitial lung disease. Recent data stress that identification of the autoantibody specificity allows for further prognostic stratification and therefore should be pursued.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico , Miosite/diagnóstico , Treonina-tRNA Ligase/imunologia , Adulto , Autoanticorpos/sangue , Diagnóstico Tardio , Feminino , Mãos/patologia , Humanos , Miosite/tratamento farmacológicoRESUMO
Anti-PL7 antibodies to threonyl-tRNA synthetase purified from beef liver were observed in the serum of a dermatopolymyositis patient. They were identified by CIE and DID using a standard anti-PL7 antiserum and quantified by ELISA in serum samples taken over a five year period. The level of antibodies against not only threonyl-tRNA synthetase but also several muscle proteins including tropomyosin, was strongly correlated with disease activity and treatment. This correlation may prove important both in monitoring the response of the patient to treatment and to our understanding of the aetiology of the disease.
Assuntos
Aminoacil-tRNA Sintetases/imunologia , Anticorpos Antinucleares/análise , Dermatomiosite/imunologia , Treonina-tRNA Ligase/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Proteínas Musculares/imunologiaRESUMO
Several trends become evident from the foregoing discussion. As the different ANA antigenic specificities have been identified, they have often been found to be highly conserved polypeptides that subserve very basic cellular functions that are carried out in the nucleus, nucleolus, and ribosomes. The reasons why only 30 or so basic cellular proteins become the targets of an autoimmune response in patients with connective tissue disease at the exclusions of the other 10,000 macromolecules that exist inside cells remain a mystery. However, some insight into this enigma might be provided by the mechanism of molecular mimicry (Table 9). The possibility that highly conserved immunogenic molecules that are expressed by infectious pathogens can trigger an immune response in a genetically predisposed human host that cross-reacts with cellular autoantigens is a well documented phenomenon in disorders such as rheumatic fever. This mechanism is now being mentioned with increasing frequency in discussions pertaining to the pathogenesis of autoimmune connective tissue diseases. Another trend relates to the increasing sensitivity of the newer assays that have been developed to detect ANA. When highly purified or recombinant autoantigens are used in versatile assays such as ELISA, radioimmunoassays, or immunoprecipitation, the frequency with which certain autoantibodies can be detected in patient subgroups can go up significantly. For example, with classical immunodiffusion, anti-Ro/SS-A antibodies can be detected in 25% of unselected patients with SLE, whereas with an ELISA based on affinity purified Ro/SS-A antigen, 50% of patients with SLE are found to have elevated levels of this autoantibody specificity. As is often the case, we pay for increased sensitivity in a laboratory test with decreased specificity. With immunodiffusion, virtually no normal individuals have anti-Ro/SS-A antibodies, but with the ELISA as many as 10% of normals have elevated anti-Ro/SS-A binding levels. Thus, the incremental diagnostic value of this newer anti-Ro/SS-A assay could be questioned. The true clinical value of this new laboratory technology will become more evident when these more sophisticated ANA assays are used together in a panel-like fashion to profile a given patient's autoimmune response at the very onset of his illness. Preliminary work has already begun in this area. This approach, if well standardized, could have significant diagnostic and prognostic value. Another benefit of this newer technology will be the ability to measure antibody binding levels to individual autoepitopes--limited portions of an autoantigen's amino acid sequence that represent single antibody binding sites. It is possible that certain patterns of clinical disease could be linked to autoantibody production against individual autoepitopes rather than whole autoantigenic molecules. This area is only now beginning to be explored.
Assuntos
Anticorpos Antinucleares , Dermatomiosite/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/imunologia , Formação de Anticorpos , Reações Antígeno-Anticorpo/imunologia , Sítios de Ligação de Anticorpos , Epitopos , Antígenos HLA , Humanos , Splicing de RNA/imunologia , Síndrome de Sjogren/imunologia , Treonina-tRNA Ligase/imunologiaRESUMO
OBJECTIVES: Due to the scarcity of studies in the literature, we conducted an analysis of a series of patients with the anti-PL-7, PL-12 and EJ types of antisynthetase syndrome (ASS). METHODS: We conducted a retrospective cohort study of 20 patients with ASS (8 with anti-PL-7, 6 with PL-12, 6 with EJ) monitored in our department between 1982 and 2012. RESULTS: The mean patient age at disease onset was 38.5 ± 12.9 years, and the disease duration was 4.5 ± 6.4 years. Of all the patients, 70% were white and 85% were female. Constitutional symptoms occurred in 90% of cases. All patients presented objective muscle weakness in the limbs; in addition, 30% were bedridden and 65% demonstrated high dysphagia at diagnosis. Joint and pulmonary involvement and Raynaud's phenomenon occurred in 50%, 40% and 65% of cases, respectively, with more than half of the patients presenting incipient pneumopathy, ground-glass opacity and/or pulmonary fibrosis. There were no cases of neurological and/or cardiac involvement. All patients received prednisone or other immunosuppressants depending on tolerance, side effects and/or disease refractoriness. Importantly, patients with the anti-EJ type of ASS demonstrated higher rates of recurrence. Two patients died during follow-up, and 1 patient had breast cancer at the time of diagnosis. CONCLUSIONS: ASS (anti-PL-7, PL-12 and EJ) was found to predominantly affect white women. Although the autoantibodies described in the present study are more related to pulmonary than joint involvement, our patients showed a significant percentage of both types of involvement and a high percentage of myopathy. We also observed a low mortality rate.
Assuntos
Alanina-tRNA Ligase/imunologia , Anticorpos/sangue , Glicina-tRNA Ligase/imunologia , Miosite/sangue , Miosite/imunologia , Treonina-tRNA Ligase/imunologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The aims of the present study were to determine both clinical manifestations and outcome of anti-PL7 patients with antisynthetase syndrome (ASS). METHODS: The medical records of 15 consecutive anti-PL7 patients with biopsy proven ASS were retrospectively analyzed without prior selection. RESULTS: Anti-PL7 patients exhibited polymyositis (n=14) and dermatomyositis (n=1); extra-pulmonary manifestations of ASS included: Raynaud's phenomenon (40%), mechanic's hands (33.3%), joint impairment (26.7%), pericardial effusion (20%) and esophageal/gastrointestinal involvement (20%). The outcome of myositis was as follows: remission/improvement (91.7%) and deterioration (8.3%). Fourteen patients (93.3%) experienced interstitial lung disease (ILD). ILD preceded ASS diagnosis (n=5), was identified concomitantly with ASS (n=8) and occurred after ASS diagnosis (n=1). Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n=1), progressive onset of lung signs (n=11) and asymptomatic patients exhibiting abnormalities consistent with ILD on PFT and HRCT-scan (n=2). No patient had resolution of ILD, whereas 64.3% and 35.7% experienced improvement and deterioration of ILD, respectively. ILD resulted in respiratory insufficiency requiring O2 therapy in 14.3% of cases. Two patients died. Predictive parameters of ILD deterioration were: DLCO<45% at ILD diagnosis and HRCT-scan pattern of usual interstitial pneumonia (UIP). CONCLUSION: Our series mainly underscores that ILD is frequent in anti-PL7 patients, leading to high morbidity. Our study further suggests that patients with predictive factors of ILD deterioration may require more aggressive therapy, especially the group of patients with DLCO<45% at ILD diagnosis and UIP pattern on HRCT-scan.
Assuntos
Autoanticorpos/sangue , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Treonina-tRNA Ligase/imunologia , Dermatomiosite/imunologia , Dermatomiosite/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Miosite/mortalidade , Polimiosite/imunologia , Polimiosite/mortalidade , Estudos RetrospectivosRESUMO
Autoantibodies against several aminoacyl-transfer-RNA synthetases have been described in patients with myositis; anti-threonyl-tRNA synthetase (anti-PL-7) is one of the rarest. We describe the clinical and laboratory characteristics of a cohort of European anti-PL-7 patients, and compare them with previously reported cases. This multicenter study of patients positive for anti-PL-7, identified between 1984 and 2011, derives from the EUMYONET cohort. Clinical and serologic data were obtained by retrospective laboratory and medical record review, and statistical analyses were performed with chi-squared and Fisher exact tests. Eighteen patients, 15 women, were anti-PL-7 antibody positive. Median follow-up was 5.25 years (interquartile range, 2.8-10.7 yr), and 4 patients died. All patients had myositis (12 polymyositis, 5 dermatomyositis, and 1 amyopathic dermatomyositis), 10 (55.6%) had interstitial lung disease, and 9 (50%) had pericardial effusion. Occupational exposure to organic/inorganic particles was more frequent in patients with interstitial lung disease than in the remaining patients (5 of 10 vs. 1 of 7; p = 0.152), although the difference was not significant. Concurrent autoantibodies against Ro60 and Ro52 were seen in 8 of 14 (57%) patients studied. In the literature review the most common manifestations of anti-PL-7 antisynthetase syndrome were interstitial lung disease (77%), myositis (75%), and arthritis (56%). As in other subsets of the antisynthetase syndrome, myositis and interstitial lung disease are common features of the anti-PL-7 antisynthetase syndrome. In addition, we can add pericarditis as a possible manifestation related to anti-PL-7 antibodies.