Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis

2015 ◽  
Vol 42 (12) ◽  
pp. 2412-2418 ◽  
Author(s):  
Norimoto Kobayashi ◽  
Ichiro Kobayashi ◽  
Masaaki Mori ◽  
Shinji Sato ◽  
Naomi Iwata ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Juvenile Dermatomyositis ◽  
High Titer ◽  
Serum Levels ◽  
Interleukin 18 ◽  
Fatal Complication ◽  
High Resolution Computed Tomography ◽  
B Cell Activating Factor

Objective.Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5).Methods.We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography.Results.Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer.Conclusion.Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM.

Elevated serum B‐cell activating factor levels in patients with dermatomyositis: Association with interstitial lung disease

2019 ◽  
Vol 46 (12) ◽  
pp. 1190-1196
Author(s):  
Takashi Matsushita ◽  
Tadahiro Kobayashi ◽  
Miyu Kano ◽  
Yasuhito Hamaguchi ◽  
Kazuhiko Takehara
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Elevated Serum ◽  
B Cell Activating Factor

Surfactant Protein D and KL-6 as Serum Biomarkers of Interstitial Lung Disease in Patients with Scleroderma

2009 ◽  
Vol 36 (4) ◽  
pp. 773-780 ◽  
Author(s):  
FAYE N. HANT ◽  
ANNA LUDWICKA-BRADLEY ◽  
HE-JING WANG ◽  
NING LI ◽  
ROBERT ELASHOFF ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Characteristic Curve ◽  
High Sensitivity ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Receiver Operator Characteristic Curve ◽  
Surfactant Protein D ◽  
High Resolution Computed Tomography ◽  
Type Ii Pneumocytes

Objective.To assess whether serum concentrations of surfactant protein D (SP-D) and Krebs von den Lungen-6 (KL-6), glycoproteins expressed by type II pneumocytes, correlate with the presence of “alveolitis” and measures of lung function in patients enrolled in the Scleroderma Lung Study (SLS).Methods.Serum obtained at baseline screening of patients with systemic sclerosis (SSc, scleroderma) in the SLS was assayed. “Alveolitis” was defined by either bronchoalveolar lavage or thoracic high-resolution computed tomography (HRCT) by SLS criteria. SP-D and KL-6 levels were measured by ELISA in 66 SSc patients (44 with “alveolitis,” 22 without “alveolitis”) and in 10 healthy controls. These were compared to clinical measures of lung disease and “alveolitis” in the SLS patients.Results.SP-D levels were 300 ± 214 ng/ml (mean ± SD) in the SSc patients compared to 40 ± 51 ng/ml in controls (p < 0.0001). KL-6 levels were 1225 ± 984 U/ml in the SSc patients and 333 ± 294 U/ml in controls (p < 0.0001). SSc patients with “alveolitis” had higher levels of both SP-D and KL-6 than those without “alveolitis.” The level of SP-D was 353 ± 219 ng/ml in patients with “alveolitis” and 161 ± 143 ng/ml without “alveolitis” (p = 0.0002). The level of KL-6 was 1458 ± 1070 U/ml in patients with “alveolitis” and 640 ± 487 U/ml without “alveolitis” (p = 0.0001). Receiver operator characteristic curve analysis demonstrated high sensitivity and specificity of both SP-D and KL-6 for the determination of “alveolitis.” KL-6 and SP-D were positively correlated with maximum fibrosis scores, but not with maximum ground-glass opacities, on HRCT.Conclusion.Serum levels of SP-D and KL-6 appear to be indicative of “alveolitis” in SSc patients as defined by the SLS, and are significantly higher than in SSc patients without “alveolitis.” Serum SP-D and KL-6 may serve as noninvasive serological means of assessing interstitial lung disease in patients with SSc.

scholarly journals Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

2020 ◽  
Author(s):  
Yueyan Lou ◽  
yu zheng ◽  
Xiaoming Tan ◽  
Bijun Fan ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Serum Levels ◽  
Clinical Severity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Disorder ◽  
Healthy Controls ◽  
Serum Samples ◽  
High Resolution Computed Tomography ◽  
Highly Correlated

Abstract Background: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. Methods: Serum samples of 40 DM-ILD patients and 30 healthy controls were collected. Expressions of S100A8/A9 were analyzed by enzyme-linked immunosorbent assay (ELISA) and interleukins were analyzed by cytometric beads array (CBA). Results: Serum IL-4, IL-6 and S100A8/A9 were observably higher in DM-ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = -0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = -0.2066, p = 0.0061, FVC%: r = -0.2156, p = 0.0050). Conclusions: Serum level of S100A8/A9 may be a valuable marker for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD. Keywords : Dermatomyositis, Interstitial lung disease, S100A8/A9, Interleukin

scholarly journals Higher circulatory HMGB1 accelerates postoperative acute exacerbation of interstitial lung disease in lung cancer

2020 ◽  
Author(s):  
Kakuhiro Yamaguchi ◽  
Satoshi Nakao ◽  
Hiroshi Iwamoto ◽  
Atsushi Kagimoto ◽  
Yoshinori Handa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Acute Exacerbation ◽  
Scoring System ◽  
Operative Time ◽  
High Mobility ◽  
Serum Levels ◽  
Molecular Target ◽  
Fatal Complication

Abstract Background: Postoperative acute exacerbation of interstitial lung disease (AE-ILD) is a fatal complication in patients with lung cancer and ILD, and it needs to be overcome to improve the long-term outcomes of these patients. However, the molecular target for predicting and preventing this fatal complication remains unclear. High-mobility group box 1 (HMGB1), which is reported to increase due to surgical procedure, activates a pro-inflammatory response associated with acute lung injury. This study aimed to elucidate the association between postoperative AE-ILD and circulatory HMGB1, especially focusing on its predictive potential. Methods: This study included 152 patients with lung cancer and ILD, who underwent radical surgery between January 2011 and August 2019. We measured HMGB1 serum levels, and investigated the factors affecting HMGB1 and the predictive potential of HMGB1 for postoperative AE-ILD.Results: Postoperative AE-ILD was developed in 17 (11.2%) of 152 patients with lung cancer and ILD. HMGB1 serum levels in patients with AE-ILD were significantly higher than those in patients without (median [IQR]: 5.39 [3.29-11.70] ng/mL vs 3.55 [2.07-5.62] ng/mL). Logistic regression analysis revealed that HMGB1 higher levels and longer operative time was independently associated with a higher incidence of postoperative AE-ILD. Furthermore, when HMGB1 and operative time were incorporated into previously reported risk scoring system, the concordance index was 0.876 which is statistically higher than 0.715 calculated by reported scoring system only.Conclusions: Baseline levels of serum HMGB1 could be a promising biomarker for predicting postoperative AE-ILD, especially when combined with operative time. HMGB1 may be a molecular target of this fatal complication to be overcome.

scholarly journals Serum B cell–activating factor (BAFF) level in connective tissue disease associated interstitial lung disease

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Tsutomu Hamada ◽  
Takuya Samukawa ◽  
Tomohiro Kumamoto ◽  
Kazuhito Hatanaka ◽  
Go Tsukuya ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
B Cell ◽  
Connective Tissue Disease ◽  
B Cell Activating Factor ◽  
Baff Level

scholarly journals Erratum to: Serum B cell–activating factor (BAFF) level in connective tissue disease associated interstitial lung disease

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Tsutomu Hamada ◽  
Takuya Samukawa ◽  
Tomohiro Kumamoto ◽  
Kazuhito Hatanaka ◽  
Go Tsukuya ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
B Cell ◽  
Connective Tissue Disease ◽  
B Cell Activating Factor ◽  
Baff Level

scholarly journals A rare case of Interstitial lung disease complicated by overlapping syndrome with obstructive ventilatory dysfunction as the first symptom

2021 ◽  
Vol 3 (4) ◽  
pp. 1-5
Author(s):  
Yuling LIANG ◽  
Yan LEI ◽  
Jiaqi XU ◽  
Liqi HUANG ◽  
Lian LIN ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cyclic Peptide ◽  
Interstitial Fibrosis ◽  
High Titer ◽  
High Resolution Computed Tomography ◽  
Respiratory Dysfunction ◽  
The Past ◽  
Pulmonary Interstitial Fibrosis ◽  
Function Test

Interstitial lung disease is often a serious complication of connective tissue disease（CTD）, representing the first cause of death in CTD. However, there are few reports of SSc-RA overlap-associated interstitial pneumonia. Respiratory dysfunction as the first clinical manifestation is even rarely reported. We herein described a case of a male patient who developed significant respiratory dysfunction as the principal clinical sign for the past 6 months, plus newly developed skin thickening in bilateral upper limbs and pain and swelling of multiple joints for the past 6 weeks. Extensive immunological screening showed high titer of antinuclear antibodies(ANA), rheumatoid factor(RF), anti-cyclic peptide containing citrulline (anti-CCP)，and positive anti-Scl-70 antibody. Chest high resolution computed tomography(HRCT) was performed and hence ILD was confirmed. Pulmonary function test (PFT) revealed obstructive ventilatory dysfunction rather than restrictive ventilatory dysfunction. So bronchodilation test was performed and asthma was considered. Finally, after a multidisciplinary team (MDT) discussion, the diagnosis of asthma and ILD associated with SSc-RA overlap was established. It is important to note that CTD associated pulmonary interstitial fibrosis must be considered as the differential diagnosis of any newly diagnosed interstitial pulmonary disease. In addition, if patient with dyspnea is highly suspicious of pulmonary interstitial fibrosis, bronchodilation test is still needed to exclude asthma in order to avoid misdiagnosis.

scholarly journals AB0605 CLINICAL PROFILE AND CHEST HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) FINDINGS IN PATIENTS WITH CONNECTIVE TISSUE DISEASES AND INTERSTITIAL LUNG DISEASE: EXPERIENCE OF A SINGLE REFERENCE RHEUMATOLOGY CENTER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1598.2-1599
Author(s):  
I. Rusu ◽  
L. Muntean ◽  
M. M. Tamas ◽  
I. Felea ◽  
L. Damian ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
High Resolution Computed Tomography ◽  
Hrct Patterns

Background:Interstitial lung disease (ILD) is a common manifestation of connective tissue diseases (CTDs), and is associated with significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) play an important role in the diagnosis of ILD and may provide prognostic information.Objectives:We aimed to characterize the clinical profile and chest HRCT abnormalities and patterns of patients diagnosed with CTDs and ILD.Methods:In this retrospective, observational study we included 80 consecutive patients with CTDs and ILD referred to a tertiary rheumatology center between 2015 and 2019. From hospital charts we collected clinical data, immunologic profile, chest HRCT findings. HRCT patterns were defined according to new international recommendations.Results:Out of 80 patients, 64 (80%) were women, with a mean age of 55 years old. The most common CTD associated with ILD was systemic sclerosis (38.8%), followed by polymyositis (22.5%) and rheumatoid arthritis (18.8%). The majority of patients had dyspnea on exertion (71.3%), bibasilar inspiratory crackles were present in 56.3% patients and 10% had clubbing fingers. Antinuclear antibodies (ANA) were present in 78.8% patients, and the most frequently detected autoantibodies against extractable nuclear antigen were anti-Scl 70 (28.8%), followed by anti-SSA (anti-Ro, 17.5%), anti-Ro52 (11.3%) and anti-Jo (7.5%). Intravenous cyclophosphamide therapy for 6-12 months was used in 35% of patients, while 5% of patients were treated with mycophenolate mofetil.The most frequent HRCT abnormalities were reticular abnormalities and ground glass opacity. Non-specific interstitial pneumonia (NSIP) was identified in 46.3% CTDs patients. A pattern suggestive of usual interstitial pneumonia (UIP) was present in 32.5% patients, mainly in patients with systemic sclerosis. In 21.3% patients the HRCT showed reticulo-nodular pattern, micronodules and other abnormalities, not diagnostic for UIP or NSIP pattern.Conclusion:Nonspecific interstitial pneumonia (NSIP) is the most common HRCT pattern associated with CTDs. Further prospective longitudinal studies are needed in order to determine the clinical and prognostic significance of various HRCT patterns encountered in CTD-associated ILD and for better patient management.References:[1]Ohno Y, Koyama H, Yoshikaua T, Seki S. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD). Curr Rheumatol Rep. 2015;17(12):69.[2]Walsh SLF, Devaraj A, Enghelmeyer JI, Kishi K, Silva RS, Patel N, et al. Role of imaging in progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150)Disclosure of Interests:None declared

scholarly journals Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association

2021 ◽  
Vol 10 (12) ◽  
pp. 2548
Author(s):  
Marco Sebastiani ◽  
Fabrizio Luppi ◽  
Gianluca Sambataro ◽  
Diego Castillo Villegas ◽  
Stefania Cerri ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Rheumatic Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Usual Interstitial Pneumonia ◽  
Clinical History ◽  
High Resolution Computed Tomography ◽  
Function Testing ◽  
And Diffusion

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

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

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