scholarly journals Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongpeng Ge ◽  
Hanbo Yang ◽  
Xinyue Xiao ◽  
Lin Liang ◽  
Xin Lu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Signal Recognition Particle ◽  
Ground Glass Opacity ◽  
Signal Recognition ◽  
High Resolution Computed Tomography ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Long Term Follow Up

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.

scholarly journals Development of Necrotizing Myopathy Following Interstitial Lung Disease with Anti-signal Recognition Particle Antibody

2018 ◽  
Vol 57 (14) ◽  
pp. 2045-2049 ◽  
Author(s):  
Tatsuya Kusumoto ◽  
Satoshi Okamori ◽  
Keita Masuzawa ◽  
Takanori Asakura ◽  
Naoshi Nishina ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Signal Recognition Particle ◽  
Signal Recognition ◽  
Necrotizing Myopathy

scholarly journals The expression of BAFF in the muscles correlate with refractory autoimmune necrotizing myopathy with anti-signal recognition particle antibodies

2020 ◽  
Author(s):  
Yawen Zhao ◽  
Wei Zhang ◽  
Yilin Liu ◽  
Zhaoxia Wang ◽  
Yun Yuan
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Muscle Weakness ◽  
B Lymphocyte ◽  
Clinical Symptoms ◽  
Fatty Infiltration ◽  
Signal Recognition Particle ◽  
Response To Therapy ◽  
Signal Recognition ◽  
Necrotizing Myopathy

Abstract BackgroundAutoimmune necrotizing myopathy with anti-signal recognition particle antibodies (ANM-SRP) is considered as a refractory myositis; some patients respond poorly to conventional immunosuppression，required the treatment of B lymphocyte clearance. We aimed to identify the factors related to refractory ANM-SRP.Results48 patients with ANM-SRP were included to identify the factors related to refractory ANM-SRP. We monitored the clinical symptoms and image changes over 12 months. Refractory ANM-SRP appeared in 32.5% patients, who showed no or minimal improvement after 12 months with steroid therapy. The clinical risk factors for refractory patients were male (19.57, 1.49-256.53), severe muscle weakness (7.51, 41.03-54.88) and concurrent interstitial lung disease (39.70, 3.04-518.38). The fatty infiltration rate of thigh muscles over 3 months was more severe (P=0.022) in refractory patients. Muscles of all patients underwent routine histology, enzyme histochemistry and immunohistochemistry staining. The first antibodies used for immunohistochemistry include anti-B cell activating factor (BAFF) and BAFF receptor (BAFF-R) antibodies. Immunohistochemical staining and western bolt showed that the expression of BAFF and BAFF-R in muscles of the patients were higher than that of the normal controls. The positive BAFF-R cells (P=0.036) and CD19 positive lymphocytes (P=0.002) in refractory patients were higher than in patients with good clinical response to therapy.ConclusionThe expression of BAFF and BAFF-R in muscles of ANM-SRP were upregulated. Male, severe muscle weakness, concurrent interstitial lung disease, quick development of muscle fatty infiltration and more BAFF-R and B-lymphocytes infiltration in muscle indicate a poor response to immunosuppressive therapy.

scholarly journals Factors associated with refractory autoimmune necrotizing myopathy with anti-signal recognition particle antibodies

2020 ◽  
Author(s):  
Yawen Zhao ◽  
Wei Zhang ◽  
Yilin Liu ◽  
Zhaoxia Wang ◽  
Yun Yuan
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Muscle Weakness ◽  
Fatty Infiltration ◽  
Signal Recognition Particle ◽  
Poor Response ◽  
Signal Recognition ◽  
Factors Associated ◽  
Necrotizing Myopathy

Abstract Background: Autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (ANM-SRP) is regarded as refractory myositis, whereby some patients respond poorly to conventional immunosuppression and require B cell depletion treatment. This study aimed to evaluate factors associated with refractory ANM-SRP.Results: Clinical and pathological data from 48 patients with ANM-SRP were collected. We followed up clinical symptoms and image changes over 12 months. Univariate and multivariate analyses were undertaken to determine the associations between variables of interest and poor response to therapy. Refractory ANM-SRP appeared in 32.5% of patients who showed no or minimal improvement after 12 months of steroid therapy. The clinical risk factors for refractory patients were being male (OR, 19.57; P<0.001), severe muscle weakness (OR, 7.51; P<0.001) and concurrent interstitial lung disease (OR, 39.70; P<0.001). The imaging refractory-related factor was the fatty infiltration rate of thigh muscles over 3 months (P=0.022) and the pathological factor associated with refractory ANM-SRP was the high expression of B cell activating factor receptor (BAFF-R) in muscle (P=0.036).Conclusion: Being male, severe muscle weakness, concurrent interstitial lung disease, quick development of muscle fatty infiltration and more BAFF-R and B lymphocyte infiltration in muscle indicate a poor response to immunosuppressive therapy in patients with ANM-SRP.

scholarly journals Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mouhamad Nasser ◽  
Sophie Larrieu ◽  
Loic Boussel ◽  
Salim Si-Mohamed ◽  
Fabienne Bazin ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Healthcare Resource ◽  
Pulmonary Function Tests ◽  
Healthcare Services ◽  
Resource Utilisation ◽  
High Resolution Computed Tomography ◽  
Healthcare Database ◽  
Healthcare Resource Utilisation ◽  
Kaplan Meier

Abstract Background There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. Methods The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. Results We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan–Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622–54,287) and the median annual cost per patient was €18,362 (6856–52,026), of which €11,784 (3003–42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. Conclusions This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842

scholarly journals Immune checkpoint inhibitor-associated myopathy: a clinicoseropathologically distinct myopathy

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Shahar Shelly ◽  
James D Triplett ◽  
Marcus V Pinto ◽  
Margherita Milone ◽  
Felix E Diehn ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Signal Recognition Particle ◽  
Ocular Involvement ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Coa Reductase

Abstract Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted a 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analysed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range 28–86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of the immune-mediated necrotizing myopathy patients (P &lt; 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of the immune-mediated necrotizing myopathy patients (P &lt; 0.001). Median creatine kinase was 686 IU/l in the immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/l in immune-mediated necrotizing myopathy cohort (P &lt; 0.001). Lymphopenia was observed in 18 and 7 patients with and without immune checkpoint inhibitor exposure, respectively (P &lt; 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibres with no or subtle inflammation. Necrotic fibres however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of the immune checkpoint inhibitor-naïve patients (P &lt; 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibres was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had a higher frequency of mitochondrial abnormalities and less number of regenerating fibres than immune-mediated necrotizing myopathy patients (P &lt; 0.001). Anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favourably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibres and not accompanied by anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis.

scholarly journals Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Liang ◽  
Ya-Mei Zhang ◽  
Ya-Wen Shen ◽  
Ai-Ping Song ◽  
Wen-Li Li ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Disease Activity ◽  
Lung Disease ◽  
Longitudinal Studies ◽  
Type I ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Necrotizing Myopathy ◽  
Immune Mediated

BackgroundDermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD.MethodsA total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated in vitro.ResultsSerum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all p &lt; 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9–44.7) vs. 16.2 (10.0–26.9) ng/mL, p &lt; 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 ± 2.3 ng/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 ± 0.3 ng/mL, p = 0.022) and healthy controls (1.4 ± 1.2 ng/mL, p = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 (r = 0.659, p = 0.020) and IFIH1 (r = 0.787, p = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD. In vitro stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.ConclusionsAmong anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.

scholarly journals Increased levels of HE4 (WFDC2) in systemic sclerosis: a novel biomarker reflecting interstitial lung disease severity?

2020 ◽  
Vol 11 ◽  
pp. 204062232095642
Author(s):  
Mingxia Zhang ◽  
Liyun Zhang ◽  
Linning E ◽  
Ke Xu ◽  
Xu Fei Wang ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Lavage Fluid ◽  
Ct Scans ◽  
Function Parameter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
High Resolution Computed Tomography

Background: Human epididymis protein 4 (HE4, also known as WFDC-2) has been implicated in fibrotic disorders pathobiology. We tested the hypothesis that HE4 may be used as a candidate biomarker for systemic sclerosis (SSc)-related interstitial lung disease (SSc-ILD). Methods: A total of 169 consecutive SSc patients and 169 age-and sex-matched healthy controls were enrolled and blood samples were collected. Pulmonary function tests (PFTs) and paired lavage was performed on 169 patients and 37 healthy controls. All patients were classified as having SSc-no ILD or SSc-ILD, based on high-resolution computed tomography (CT) scans of the chest, and a semiquantitative grade of ILD extent was evaluated through CT scans (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%). Serum and bronchoalveolar lavage fluid (BALF) HE4 levels were measured by enzyme-linked immunosorbent assay. Results: Serum HE4 levels were higher in SSc patients [median (interquartile range), 139.4 (85.9–181.8) pmol/l] compared with healthy controls [39.5 (24.3–54.2) pmol/l, p < 0.001] and were higher in patients with SSc-ILD [172.1 (94.8–263.3) pmol/l] than in those with SSc-no ILD [97.4 (85.5–156.5) pmol/l, p < 0.001]. This observation was replicated in the BALF samples. Corresponding values were 510.8 (144.6–1013.8) pmol/l for SSc cohort, 754.4 (299–1060) pmol/l for SSc-ILD, 555.1 (203.7–776.2) pmol/l for SSc-no ILD, and 238.7 (97.7–397.6) pmol/l for controls. The semiquantitative grade of ILD on CT scan was significantly proportional to the HE4 levels and the lung function parameter (i.e., FVC) had a negative correlation with the HE4 levels. Conclusion: This is the first study to demonstrate the potential clinical utility of blood and BALF HE4 as a biomarker for SSc-ILD. Future prospective validation studies are warranted.

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