RESUMEN

BACKGROUND: Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. METHODS: This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth's logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. RESULTS: This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. CONCLUSIONS: Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.

Asunto(s)

Autoanticuerpos , Enfermedades Pulmonares Intersticiales , Miositis , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Miositis/inmunología , Miositis/epidemiología , Miositis/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Adulto , Anciano , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Ribonucleoproteínas/inmunología

RESUMEN

Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.

Asunto(s)

Autoanticuerpos , Pulmón , Miositis , Glándulas Salivales , Humanos , Glándulas Salivales/inmunología , Glándulas Salivales/patología , Autoanticuerpos/inmunología , Miositis/inmunología , Femenino , Masculino , Pulmón/inmunología , Pulmón/patología , Persona de Mediana Edad , Líquido del Lavado Bronquioalveolar/inmunología , Adulto , Linfocitos B/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Autoantígenos/inmunología , Anticuerpos Antinucleares/inmunología , Anciano

RESUMEN

A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased. A bronchoalveolar lavage fluid (BALF) examination revealed amorphous globules and alveolar macrophages with eosinophilic granules. Owing to negative anti-GM-CSF antibody tests, a diagnosis of secondary pulmonary alveolar proteinosis (PAP) was established.

RESUMEN

Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, n = 52) and discrepant (negative on RNA-IP, n = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (p < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD.

Asunto(s)

Aminoacil-ARNt Sintetasas , Autoanticuerpos , Ensayo de Inmunoadsorción Enzimática , Inmunoprecipitación , Humanos , Masculino , Aminoacil-ARNt Sintetasas/inmunología , Femenino , Inmunoprecipitación/métodos , Persona de Mediana Edad , Autoanticuerpos/sangre , Adulto , Anciano , Miositis/inmunología , Miositis/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/diagnóstico , ARN

RESUMEN

Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.

Asunto(s)

Aminoacil-ARNt Sintetasas , Dermatomiositis , Miositis , Tirosina-ARNt Ligasa , Humanos , Autoanticuerpos

RESUMEN

A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.

RESUMEN

Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are useful for identifying a clinical subset of patients with inflammatory myopathies. Since the myositis of anti-ARS-positive patients is characterized by a unique set of non-myopathic manifestations, including interstitial lung disease, mechanic's hands, and arthralgia, the patients are classified as having anti-synthetase syndrome. Autoantibodies have been identified to eight kinds of ARSs. Of the other 12 ARSs, eight are components of the "OJ" multi-synthetase complex. Autoantibodies to the four remaining ARSs (CysARS, ValARS, SerARS, and TrpARS) have not been reported to be present in patients with inflammatory myopathies. In this study, we first screened samples from more than 300 Japanese patients majorly consisting of those with dermatomyositis (DM) by our established in-house ELISA to find autoantibodies against the four ARSs described above. Since sera from two DM patients specifically reacted to CysARS or ValARS, we determined their reactivities by immunoprecipitation (IP) with the corresponding recombinant proteins and IP-Western blotting with cellular extract. One patient had several features found in anti-synthetase syndrome, but the other did not. The clinical differences among the various anti-ARS antibodies should be explored in a future work.

Asunto(s)

Aminoacil-ARNt Sintetasas , Autoanticuerpos , Miositis , Valina-ARNt Ligasa , Humanos , Aminoacil-ARNt Sintetasas/inmunología , Miositis/inmunología , Miositis/patología , Síndrome , Valina-ARNt Ligasa/inmunología

RESUMEN

A 59-year-old man who had smoked for 23 pack-years was admitted to our hospital because of two-month history of back pain. The chest computed tomography scan demonstrated combined pulmonary fibrosis and emphysema (CPFE) and an irregular shaped nodule in the left lower lobe of the lung. A biopsy obtained from samples from subcarinal lymph nodes revealed non-small cell lung cancer. Anti-aminoacyl-tRNA synthetase (ARS) antibody was elevated up to 166 U/mL, although he had no symptoms suggestive connective tissue diseases. It is well known that most of CPFE patients are current or former heavy smokers, and some researchers described the relationship between CPFE and connective tissue diseases. To our best knowledge, this was the first report of lung cancer in patient with anti-ARS antibody-positive CPFE. In some anti-ARS antibody-positive patients, smoking might have a relationship with development of CPFE and lung cancer.

Asunto(s)

Aminoacil-ARNt Sintetasas , Carcinoma de Pulmón de Células no Pequeñas , Enfermedades del Tejido Conjuntivo , Enfisema , Neoplasias Pulmonares , Enfisema Pulmonar , Fibrosis Pulmonar , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/diagnóstico por imagen , Estudios Retrospectivos

RESUMEN

BACKGROUND: Obesity is a major risk factor for developing various respiratory diseases. Patients with anti-aminoacyl tRNA synthetase (ARS) antibodies often have interstitial lung disease (ILD). The present study was conducted to evaluate the association between obesity and outcomes of anti-ARS antibody-related ILD (ARS-ILD). METHODS: We retrospectively investigated 58 patients with ARS-ILD and compared the clinical characteristics, treatment, and prognoses between obese (body mass index [BMI] ≥25 kg/m2) and nonobese (BMI <25 kg/m2) patients. Chest fat was quantified via computed tomography (CT). Thoracic subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured at diagnosis and first relapse of ILD. RESULTS: Sixteen patients were obese. Obese patients had lower percentages of predicted diffusing capacity of the lungs for carbon monoxide and higher high-resolution CT scores and SAT and VAT indexes than did nonobese patients. The ILD relapse rate was higher in obese patients (P < 0.01), especially among those with high SAT indexes (P < 0.01). The SAT and VAT indexes increased significantly from diagnosis until first relapse. Among clinical parameters at first relapse, SAT and VAT indexes were correlated with serum Krebs von den Lungen-6 levels (r = 0.720, P = 0.008) and total ground-glass attenuation scores (r = 0.620, P = 0.024), respectively. CONCLUSIONS: Obesity and high SAT indexes are risk factors for ILD relapse in patients positive for anti-ARS antibodies. Evaluating and quantifying patients' chest fat on CT is important for predicting ILD relapse.

Asunto(s)

Aminoacil-ARNt Sintetasas , Enfermedades Pulmonares Intersticiales , Autoanticuerpos , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Obesidad/complicaciones , Estudios Retrospectivos

RESUMEN

Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of central and peripheral vascular disorders, including carotid, coronary and peripheral arterial diseases, and Raynaud's phenomenon. Recently, associations of plasma homocysteine levels with autoimmune diseases such as systemic lupus erythematodes and systemic sclerosis have been reported. However, no study analyzed the association between plasma homocysteine levels and dermatomyositis (DM). The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with DM. Plasma homocysteine levels in 28 Japanese patients with DM and 22 healthy controls were examined. We found that the plasma homocysteine levels in DM patients were significantly higher than those in healthy individuals (15.8 ± 1.1 vs 8.5 ± 0.5 µmol/L, P < 0.01). Presence of mechanic's hand, complication of interstitial lung disease (ILD), high serum Krebs von den Lungen-6 (KL-6), surfactant protein-D and creatine kinase levels, and anti-aminoacyl-tRNA synthetase (ARS) antibody (Ab) positivity were significantly more prevalent among DM patients with elevated plasma homocysteine levels. The plasma homocysteine levels in DM patients with mechanic's hand, ILD and anti-ARS Ab were significantly higher than those in DM without those features. Furthermore, the plasma homocysteine levels were positively correlated with serum KL-6 levels. These results suggest that the pathogenesis of elevated plasma homocysteine levels may be associated with ILD in DM patients, especially with anti-ARS Ab, and further examination is required.

Asunto(s)

Aminoacil-ARNt Sintetasas , Dermatomiositis , Enfermedades Pulmonares Intersticiales , Autoanticuerpos , Dermatomiositis/complicaciones , Homocisteína , Humanos , Enfermedades Pulmonares Intersticiales/etiología

RESUMEN

A 55-year-old man who had been diagnosed with autoimmune pancreatitis five years earlier was referred to our department because of finger swelling, finger stiffness and the presence of interstitial lung disease (ILD). The patient was diagnosed with Sjögren's syndrome according to the pathological findings of minor salivary glands and positive anti-SS-A antibodies. Later, at age 58, he was hospitalised due to the exacerbation of the ILD. Serum IgG4 level was checked and was found to be elevated (417 mg/dL). After the introduction of cyclosporine in addition to the prednisolone, at age 60, the ILD disease activity stabilised. However, at age 62, fever, myalgia and mechanic's hands appeared. His serum creatine kinase level was high, and magnetic resonance imaging showed inflammatory findings of muscle. In-house ELISA clarified that his serum carried anti-PL-7 antibody among anti-aminoacyl-tRNA synthetase antibodies. This is a unique case who had overlapping features of IgG4-related autoimmune pancreatitis, Sjögren's syndrome and anti-synthetase syndrome. Although the aetiology of the complications in this patient is obscure, autoimmunity might have played a significant role in the disease conditions and prognosis of the present case with IgG4-related disease.

Asunto(s)

Pancreatitis Autoinmune/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Miositis/complicaciones , Síndrome de Sjögren/complicaciones , Aminoacil-ARNt Sintetasas/sangre , Autoanticuerpos/sangre , Pancreatitis Autoinmune/diagnóstico , Creatina Quinasa/sangre , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miositis/sangre , Miositis/diagnóstico , Glándulas Salivales Menores/inmunología , Glándulas Salivales Menores/patología

RESUMEN

Objective: To provide reference for clinicians in diagnosis and treatment of antisynthetase syndrome with interstitial pulmonary disease (ASS-ILD) by analyzing the clinical features, imaging features and pulmonary function changes of ASS-ILD patients. Methods: A total of 92 patients with ASS-ILD diagnosed in the Respiratory Center of China-Japan Friendship Hospital from January 2015 to May 2018 were included, clinical manifestations, high-resolution computed tomography (HRCT), pulmonary function test, treatment and outcome were retrospectively analyzed. Results: The average age of the 92 patients was (58.6±12.2) years with a ratio of male to female 1∶1.79. The main types of anti-synthetase antibody were anti-Jo-1 antibody (37 cases, 40.2%) and anti EJ antibody (26 cases, 28.3%). The most common symptoms of ASS-ILD were cough (79 cases, 85.9%), shortness of breath (60 cases, 65.2%), expectoration (54 cases, 58.7%), fever (34 cases, 36.9%), and common signs were craftsman's hand (30 cases, 32.6%) and joint pain (23 cases, 25.0%). The most common imaging findings in HRCT were ground-glass opacities(68 cases, 73.9%), reticulations (45 cases, 48.9%), tractive bronchiectasis (40 cases, 43.5%) and consolidation (39 cases, 42.4%). The most common types of ILD were non-specific interstitial pneumonia (NSIP) (63 cases, 68.5%), followed by NSIP-organic pneumonia (OP) (12 cases, 13.0%). The main type of lung function impairment was mild restrictive ventilation dysfunction. There were no significant differences in clinical features, imaging findings and pulmonary function changes in different subtypes of ASS-ILD patients (all P>0.05). Corticosteroids was used in 78 (84.8%) of ASS-ILD patients, and 34 cases (37.0%) were given cyclophosphamide. A total of 91 patients (98.9%) were discharged with improvement and 1 anti-EJ positive patient died. Conclusions: ASS-ILD occurs frequently in middle-aged and old women. Respiratory symptoms, craftsman's hands and arthritis are the most common clinical manifestations. The most common imaging types of ILD are NSIP and NSIP-OP. Corticosteroids is commonly used for treatment.

Asunto(s)

Enfermedades Pulmonares Intersticiales , Miositis , Anciano , China , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

BACKGROUND: Anti-synthetase syndrome (ASS) is characterized by the presence of anti-aminoacyl-tRNA synthetase antibody and ASS-associated interstitial lung disease (ILD) often recurs. The effectiveness of remission induction therapy with corticosteroids and calcineurin inhibitor (CNI) and the predictive factors for ASS-ILD recurrence were examined. METHODS: We retrospectively identified consecutive patients with ASS-ILD treated with corticosteroids and CNI during 2006-2017 and evaluated the predictive factors for recurrence using logistic regression analysis. RESULTS: Of the 57 patients included in this study, 54 (94.7%) exhibited improved response to remission induction therapy. There were 32 recurrence patients during maintenance therapy. The median period until recurrence was 27 months. There were no significant differences in the baseline characteristics between the recurrence and nonrecurrence groups. In the recurrence group, respiratory function and St. George's Respiratory Questionnaire score deteriorated over the clinical course. The Krebs von den Lungen-6 (KL-6) level changed with disease behavior. The multivariate analysis revealed that KL-6 increase rate from remission (odds ratio: 3.21, 95% CI: 1.17-8.86, p = 0.02) and CNI discontinuation (odds ratio: 8.09, 95% CI: 1.39-47.09, p = 0.02) were independent predictive factors for recurrence. The receiver operating characteristics analysis revealed that the optimal cut-off point of KL-6 increase rate was 2.0. The positive predictive values of the KL-6 increase rate from remission of >2.0 and CNI discontinuation were 90.0 and 88.9%, respectively. The CNI treatment duration and recurrence were not related. CONCLUSIONS: Recurrence influenced long-term deterioration. KL-6 was a serum biomarker for disease behavior and recurrence prediction. The results suggest the importance of CNI continuation.

Asunto(s)

Aminoacil-ARNt Sintetasas/inmunología , Anticuerpos , Enfermedades Pulmonares Intersticiales/inmunología , Predicción , Humanos , Recurrencia

RESUMEN

BACKGROUND AND PURPOSE: Patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies frequently experience complications of interstitial pneumonia (ARS-IP), and the computed tomography (CT) of ARS-IP frequently shows nonspecific interstitial pneumonia (NSIP) pattern. The CT pattern of ARS-IP might be different from that of idiopathic IP. However, the clinical differences in patients with ARS-IP and idiopathic IP showing the similar CT patterns have not yet been well studied. The objective of this study was to evaluate the clinical differences between patients with ARS-NSIP and idiopathic NSIP (I-NSIP). METHODS: Two groups of 34 patients each, with ARS-NSIP and I-NSIP, who visited Hiroshima University Hospital between January 2005 and December 2017, were enrolled. Clinical features and outcomes were retrospectively compared between the two groups. RESULTS: The ARS-NSIP group included more female patients and significantly younger patients than the I-NSIP group. The percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) was significantly higher, and the CD4/CD8 ratio in BALF was significantly lower in the ARS-NSIP group compared with the I-NSIP group. The proportion of patients with traction bronchiectasis detected by CT was significantly higher in I-NSIP compared with ARS-NSIP. The number of patients who received corticosteroid and/or immunosuppressant therapy was significantly larger in the ARS-NSIP group than in the I-NSIP group. In addition, the patients in the I-NSIP group who underwent the immunosuppressive therapy demonstrated shorter survival than those who underwent no treatment; this tendency was not observed in the ARS-NSIP group. The 10-year survival rate of patients in the ARS-NSIP group was significantly higher than that of patients in the I-NSIP group (91.8% vs. 43.0%; log-rank, p = 0.012). The multivariate survival analysis revealed that positive anti-ARS antibody was an independent favorable prognostic factor in the patients with NSIP (OR, [95% CI]:0.12 [0.02-0.55], p = 0.013). CONCLUSIONS: Patients with ARS-NSIP had a significantly better prognosis than those with I-NSIP; this may be associated with the sensitivity to immunosuppressive therapies, and the different findings of BALF and HRCT between the two groups.

Asunto(s)

Aminoacil-ARNt Sintetasas/antagonistas & inhibidores , Líquido del Lavado Bronquioalveolar/inmunología , Neumonías Intersticiales Idiopáticas/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/inmunología , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/epidemiología , Relación CD4-CD8/métodos , Femenino , Humanos , Neumonías Intersticiales Idiopáticas/diagnóstico por imagen , Neumonías Intersticiales Idiopáticas/tratamiento farmacológico , Neumonías Intersticiales Idiopáticas/fisiopatología , Inmunosupresores/uso terapéutico , Japón/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/fisiopatología , Linfocitos/citología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/métodos

RESUMEN

Transbronchial lung cryobiopsy (TBLC) is a useful and safe method for the diagnosis of interstitial lung disease (ILD). Herein, we describe the cases of two patients who developed ILD from anti-aminoacyl-tRNA synthetase syndrome with respiratory failure. TBLC was performed instead of surgical lung biopsy. There were no complications, and sufficient specimens were harvested to make the precise histopathological diagnosis. TBLC should be considered as a critical approach for the histopathological diagnosis of ILD in patients who cannot undergo surgical lung biopsy because of respiratory failure.

Asunto(s)

Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos , Biopsia/métodos , Broncoscopía/métodos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Insuficiencia Respiratoria/patología , Anciano de 80 o más Años , Ciclosporina/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Pulmón/patología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/terapia , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Prednisolona/administración & dosificación , Insuficiencia Respiratoria/inmunología , Insuficiencia Respiratoria/terapia , Síndrome

RESUMEN

OBJECTIVE: The optimal treatment strategy for anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associated interstitial lung disease (anti-ARS-PM/DM-ILD) is yet to be established. We aimed to evaluate the efficacy of glucocorticoids and calcineurin inhibitors (CNI) in patients with ARS-PM/DM-ILD. METHODS: Progression-free survival (PFS) and overall survival rates were retrospectively evaluated in 32 consecutive patients with ARS-PM/DM-ILD. Disease progression was defined as deterioration in PM/DM-ILD (including recurrence). Predictive factors associated with PFS were analyzed by Cox hazards analysis. The efficacy of first-line prednisolone (PSL) plus CNI therapy was compared with that of PSL monotherapy using propensity score-matched analysis. RESULTS: Overall, 20 (62.5%) and 12 (37.5%) patients received first-line therapy with PSL + CNI and PSL, respectively. The 2-year PFS and 5-year survival rates in the overall cohort were 68.8% and 96.9%, respectively. On multivariate analysis, arterial oxygen pressure (HR 0.86) and PSL monotherapy (vs PSL + CNI; HR 7.29) showed an independent association with PFS. Baseline characteristics of propensity score-matched PSL + CNI and PSL groups were similar. The 2-year PFS rate was significantly higher in the matched PSL + CNI group than in the matched PSL group. All patients who experienced disease progression during first-line therapy were subsequently treated with second-line therapies. The 5-year survival rates of both the matched PSL + CNI and PSL groups were favorable. CONCLUSION: Propensity score-matched analysis demonstrated that first-line PSL + CNI therapy for patients with ARS-PM/DM-ILD significantly improved the PFS compared with PSL monotherapy, although there was no significant difference regarding longterm survival.

Asunto(s)

Aminoacil-ARNt Sintetasas/inmunología , Inhibidores de la Calcineurina/administración & dosificación , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/epidemiología , Glucocorticoides/administración & dosificación , Enfermedades Pulmonares Intersticiales/epidemiología , Adulto , Anciano , Aminoacil-ARNt Sintetasas/análisis , Estudios de Cohortes , Comorbilidad , Dermatomiositis/inmunología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimiositis/tratamiento farmacológico , Polimiositis/epidemiología , Polimiositis/inmunología , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Objective To investigate the clinical,serological and imaging features of antisynthetase syndrome (ASS) patients with different positive anti-aminoacyl-tRNA synthase (ARS) antibodies.Methods The demographic characteristics,major clinical data,serological parameters,high resolution CT (HRCT) imaging features and pulmonary function characteristics in 60 cases of ASS [including 42 cases with positive anti-histidine tRNA synthetase (Jo-1) antibody,and 7 cases with positive anti-threonyl tRNA synthetase (PL-7) antibody,5 cases with positive anti-alanyl tRNA synthetase (PL-12) antibody,3 cases with positive anti-glycyl tRNA synthetase (E J) antibody and 3 cases with positive anti-leucyl tRNA synthetase (OJ) antibody] were collected.The differences in ASS patients with different positive ARS antibodies were analyzed by the x2 test and Fisher exact test.Results ① The ASS with different positive ARS antibodies was common in patients with DM/PM,[60％ (36/60),28％ (17/60)],and also appeared in patients with other connective tissue diseases,such as RA(5％,3/60),SS(3％,2/60),SLE(2％,1/60),etc.With ASS diagnosed,ILD complicated with myositis was the most common clinical features (63％,38/60).Typical clinical triad syndrome (myositis,ILD and arthritis) in 52％(31/60) patients,and myositis complicated with ILD,and mechanics hands accounted for 38％ (23/60) respectively.Some patients were complicated with isolated arthritis (25％,15/60),myositis (23％,14/60) and ILD (13％,8/60).The typical triad syndrome (myositis,ILD and arthritis) only accounted for 5％(3/60).The incidence of Jo-1,EJ and OJ antibodies [71％(30/42),100％(3/3),100％(3/3)] was significantly higher than that of PL-12 antibody (20％,1/5).There was a statistically significant difference (x2=5.263,P＜0.05;x2=4.8,P＜ 0.05;x2=4.8,P＜0.05).② The positive rate of ANA was 98％(59/60).Furthermore,the fluorescence staining model of anti-OJ antibody ANA was spotted,and the other subtypes were cytosolic.The positive rate of anti-SSA-52 antibody was 45％(27/60),and there was no statistical difference between the subtypes (P＞0.05).③ The ILD incidence of different positive antibodies had no significant difference in 82％ (49/60) ASS patients with ILD.The lung function in patients with ASS-ILD showed restrictive ventilation and diffused dysfunction.Grid shadow (76％,37/49) and grind glass (35％,17/49) were the most common signs of HRCT.Nonspecific interstitial pneumonia (NSIP) (78％,38/49) was the most common subtype of ILD.The incidence of traction bronchiectasis in ASS patients with PL-12 antibody (75％,3/4) was higher than that in ASS patients with Jo-1 antibody (22％,8/36).The incidence of pleural effusion in ASS patients with OJ antibody (100％,2/2) was significantly higher than that in ASS patients with Jo-1 antibody (17％,6/36).The incidence of pericardial effusion in ASS patients with PL-7 antibody (75％,3/4) was significantly higher than that in ASS patients with Jo-1 antibody (19.4％,7/36).All the differences were statistically significant (x2=5.26,P＜0.05).The ASS-ILD lung function indicated restrictive ventilatory function and diffusion dysfunction.④ There was no significant difference in clinical data,serological indicators,ILD imaging findings,interstitial lung types and lung function between Jo-1 antibody and non-Jo-1 antibody ASS patients (P＞0.05).Conclusion The ASS with different positive ARS antibodies is very common in patients with DM/PM,and is also observed in patients with other connective tissue diseases.ILD and myositis are the most common clinical features of ASS,followed by the typical triad syndrome (myositis,ILD and arthritis).Myositis is commonly observed in ASS patients with Jo-1,EJ and OJ antibodies,while is rarely observed in ASS patients with PL-12 antibody.The diagnosis of ASS should be alert to the onset of isolated arthritis or ILD.Anti-SSA-52 antibody may be related to ASS.NSIP is the most common HRCT pattern in ASS-ILD patients.There are some differences in signs among various subtypes,indicating that the difference of fibrosis in the lung and inflammatory reactions in the body being correlated with the ASS specificities.

RESUMEN

A 65-year-old female had been treated rheumatoid arthritis (RA), interstitial pneumonia (IP) and nephrotic syndrome with prednisolone and cyclosporine. She was emergently admitted to our hospital due to the worsening exertional dyspnea and severe hypoxemia. Chest computed tomography (CT) showed new diffuse ground-glass opacities (GGOs) with slight consolidations along with bronchovascular bundle were observed in addition to pre-existing reticular shadows in both lungs with lower lobe-predominance. An acute exacerbation (AE) of pre-existing IP triggered by an infection was suspected, and the treatment with antibiotics and corticosteroid pulse therapy improved her general condition and chest radiological findings. Because some auto-antibodies associated with acute/subacute onset IP have recently become available in clinic, we examined those including anti-aminoacyl tRNA synthetase (ARS) antibodies, and found that she was positive for anti-PL-7 antibody. We diagnosed her anti-synthetase syndrome (ASS) without symptom of myositis, and her IP was considered to be ASS-related. The careful consideration is necessary to precisely diagnose and treat the patients with RA-associated interstitial lung diseases as the several etiologies may be overlapped in the same patient. J. Med. Invest. 65:147-150, February, 2018.

Asunto(s)

Aminoacil-ARNt Sintetasas/inmunología , Artritis Reumatoide/complicaciones , Autoanticuerpos/inmunología , Enfermedades Pulmonares Intersticiales/etiología , Anciano , Femenino , Humanos

RESUMEN

Objective: To describe the clinical and radiological characteristics of antisynthetase syndrome associated interstitial lung disease in patients with different serum anti-aminoacyl-tRNA synthetase antibodies. Methods: We conducted a retrospective analysis of 5 adult patients with antisynthetase syndrome associated interstitial lung disease in Peking Union Medical College Hospital. Their clinical and chest radiological data were analyzed and relevant literatures were reviewed. Results: Among these 5 patients, there were 1 male and 4 females, aged from 32 y to 67 y, with a mean age of 53 y. Cough and exertional dyspnea were the main clinical complaints. Four cases showed mechanic's-like hands, and all of the 5 cases had Velcro rales in the basal lungs. None of them showed clubbing. Creatine kinase was elevated in 1 case with anti-Jo-1 synthetase antibody, and anti-nuclear antibody was positive in 4 cases, with different titers from 1∶80 to 1∶320, and anti-Ro-52 antibody was positive in 3 cases. Anti-aminoacyl-tRNA synthetase antibody spectrum analysis showed 1 case with anti-Jo-1, 1 anti-PL-7, 1 anti PL-12, 1 anti-EJ and 1 anti-OJ synthetase antibody, respectively. Chest high resolution CT showed nonspecific interstitial pneumonia pattern in 1 case, and nonspecific interstitial pneumonia pattern with organizing pneumonia pattern in 4 cases. All the cases responded to immunosuppressive therapy including corticosteroids (with starting prednisone dosage more than 1 mg·kg(-1)·d(-1)) plus azathioprine or Mycophenolate mofetil. Conclusions: Antisynthetase syndrome associated interstitial lung disease, characterized by the presence of different anti-tRNA synthetase antibodies, is an increasingly recognized clinical entity. Clinical and radiological features of different subtypes of antisynthetase syndrome are relatively heterogeneous. Nonspecific interstitial pneumonia pattern, nonspecific interstitial pneumonia pattern with organizing pneumonia pattern and organizing pneumonia pattern were common chest HRCT patterns. Prednisone plus immunosuppressive agents are the recommended first line therapy.

Asunto(s)

Aminoacil-ARNt Sintetasas/sangre , Autoanticuerpos/sangre , Miositis/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miositis/sangre , Miositis/diagnóstico , Estudios Retrospectivos