Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody

Successful Use of Pembrolizumab to Treat Refractory Thymic Carcinoma with High PD-L1 Expression

Thymic carcinoma is a relatively rare and aggressive thymic epithelial tumor. Herein, we report successful treatment of thymic carcinoma with pembrolizumab. A 68-year-old woman was admitted to our hospital for evaluation of chest pain. Chest computed tomography showed a mass in the anterior mediastinum and lymphadenopathy in the left cervical lymph node. Analysis of biopsy specimens detected squamous cell carcinoma in the left cervical lymph node, and immunohistochemical analysis showed 100% expression of programmed death-ligand 1 (PD-L1). Masaoka-Koga stage IVb thymic carcinoma was ultimately diagnosed. Since 3 cycles of first-line chemotherapy did not result in improvement, pembrolizumab was administered as second-line treatment every 3 weeks at a dosage of 200 mg. After 3 cycles of pembrolizumab treatment, the size of the anterior mediastinal tumor and metastatic lesions had notably decreased. Pembrolizumab may prove to be an effective therapy for thymic carcinoma with high PD-L1 expression

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF

Serum autotaxin levels in chronic disease and acute exacerbation of fibrosing interstitial lung disease

Background Autotaxin (ATX) is an ecto-enzyme that catalyses the hydrolysis of lysophospholipids to the lipid mediator lysophosphatidic acid (LPA). LPA/ATX signalling has emerged as a new therapeutic target for pulmonary fibrosis; however, the serum levels and dynamics of ATX during the clinical course of fibrosing interstitial lung disease (ILD) remain unknown. This study sought to examine the serum ATX levels in fibrosing ILD in the chronic phase and in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). We aimed to elucidate the association between serum ATX level and clinical characteristics including disease progression and prognosis. Methods In total, 119 patients with fibrosing ILD and 38 healthy volunteers as controls were enrolled in the study and their serum ATX activity was analysed. We also included six male patients with AE-IPF in order to analyse the changes in serum ATX at the onset of AE-IPF. Results Patients with fibrosing ILD showed significantly higher serum ATX levels compared with healthy controls in both sexes. Per cent change in forced vital capacity after 1 year correlated with serum ATX levels in female patients. High serum ATX levels (>0.721 mg· L−1) were associated with worse outcome in survival curve and multivariate analysis of male patients. Serum ATX activity decreased after the onset of AE-IPF. Conclusion Serum ATX levels were significantly higher in patients with fibrosing ILD compared with healthy controls, and this was associated with disease progression and outcome. This suggests the potential of serum ATX as a promising biomarker for the treatment of fibrosing ILD

Association of serum high-mobility group box protein 1 level with outcomes of acute exacerbation of idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia

<div><p>Background and objective</p><p>High-mobility group box 1 (HMGB1) protein is important in acute lung injury. However, the role of HMGB-1 in acute exacerbation of fibrosing interstitial pneumonia (AE-FIP) has not been adequately studied.</p><p>Methods</p><p>We prospectively measured serum HMGB1 level from disease onset to day 7 in 36 patients with AE-FIP6 patients had missing data because of early death (within 7 days). We then examined the association of HMGB1 level and outcome, and the associations of rhTM with HMGB1 level and outcome in 19 patients who were treated with rhTM (rhTM group) and 11 patients who were not (control group).</p><p>Results</p><p>Data from 36 AE-FIP patients (mean age, 73.5±6.7years) were analyzed. Serum HMGB1 level was significantly higher in patients with AE-FIP than in those with stable idiopathic pulmonary fibrosis (16.4±13.5 vs 5.7±2.6 ng/ml, respectively; p = 0.003). HMGB1 was significantly lower on day 7 than at AE-FIP onset in survivors (6.5±4.8 vs 14.7±12.9 ng/ml, respectively; p = 0.02) but not in nonsurvivors (14.6±10.5 vs 9.2±4.8 ng/ml, respectively; p = 0.08). Although HMGB1 level at day 7 was significantly lower after rhTM treatment than at AE-FIP onset (8.4±6.1 vs 15.2±12.5 ng/ml, respectively; p = 0.02), it did not significantly decrease in patients receiving treatments other than rhTM (11.3±11.3 vs 8.3±5.3 ng/ml, respectively; p = 0.37). Three-month survival was 60.0% in the rhTM group and 36.4% in the control group (p = 0.449). In multivariate analysis, a decrease in HMGB1 was a significant independent predictor of 3-month survival (Odds ratio, 12.4; p = 0.007).</p><p>Conclusion</p><p>rhTM lowers serum HMGB1 level and may improve survival after AE-FIP. HMGB1 may be a promising therapeutic target for AE-FIP.</p></div

Serum high-mobility group box 1 protein (HMGB1) levels in patients with AE-FIP, stable IPF, and other acute lung injury, and in healthy controls.

<p>Whiskers show the minimum and maximum data values. Bars show median HMGB1 levels and the “x” indicates mean HMGB1 level. Serum HMGB-1 level was significantly higher in AE-FIP patients than in stable IPF patients and healthy controls.</p