Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

BackgroundMeasurement of serum MMP-3 levels has been considered useful to estimate the disease activity of rheumatoid arthritis (RA). We have shown that serum MMP-3 was significantly correlated with DAS28 (CRP) and could be a useful marker in predicting joint destruction1,2. CXCL13 attracts CXCR5-expressing B and helper T cells to the follicle and probably has central roles of ongoing immune activation in RA development3. Serum MMP-3 and CXCL13 have been reported as biomarkers for detecting the disease activity and predicting the therapeutic outcomes of RA4.ObjectivesThe aim of this study is to confirm the clinical significance of serum MMP-3 and CXCL13 measurement in the evaluation of disease activity and prediction of therapeutic outcome in RA patients treated with biologics.MethodsSerum MMP-3 was serially measured by MMP-3 Latex kit (Sekisui Medical Co.) for 146 RA patients before and after treatment with biologics. Number of patients treated with each biologic were 39, 28, 19, 17, 26, and 17 patients treated with abatacept, adalimumab (ADA), etanercept, golimumab, infliximab (IFX), and tocilizumab, respectively. CXCL13 was measured by ELISA kit (Quantikine human CXCL13, R&D systems) for patients treated with ADA and IFX before and 24 weeks after treatment. The patients were classified into 61 responders (good) and 85 non-responders (moderate and none) by ACR/EULAR definition of remission criteria weeks after treatment.ResultsSerum MMP-3 before the treatment was significantly increased in 146 RA patients as compared with 196 healthy subjects (196.0± 197.4 vs 58.6±27.4 ng/ml, p<0.001), and showed significant positive correlation with DAS28 (Rs=0.3842, p<0.001), but no significant difference was found between 61 responders (210.6±213 ng/ml) and 85 non-responders (185.6±186.3 ng/ml). As shown in Figure 1 (left), the MMP-3 levels gradually decreased 4, 12, and 24 weeks after successful treatment with biologics (p=0.04, p<0.001, and p<0.0001, respectively), and extent of the decrease were significantly bigger in responders than non-responders 12 and 24 weeks after treatment. Serum CXCL13 level before the treatment significantly correlated with MMP-3 levels (Rs =0.4648, p<0.001) as well as DAS28 (Rs =0.5182, p<0.001). After treatment with ADA, serum CXCL13 was significantly decreased after 24 weeks in responders as compared with non-responders (Figure 1 right, p<0.05). However, such difference was not found in patients treated with IFX. Patients with lower serum CXCL13 levels (<82.7 pg/ml) before the treatment were shown to become non-responders (p<0.07), especially their serum MMP-3 levels were low (<69.1 ng/ml).ConclusionsSerum MMP-3 and CXCL13 was shown to be useful as disease activity markers, and serial measurement were helpful to evaluate the effect of treatments with biologics. CXCL13 may be useful in evaluating and predicting the therapeutic outcome of some kinds of biologics.ReferencesMamehara A, et al: Kobe J Med Sci. 2010, 56(3): E98–107.Uemura Y, et al: Rinsho Byori. 2015, 63(12): 1357–1364 (Japanese).Mee...

Background: Although 2018 revised ISN/RPS classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between 2018 revised ISN/RPS classification and 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.Methods: We retrospectively collected medical records of 170 LN patients from the database of renal biopsy in Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as 30% decline of estimated glomerular filtration rate (eGFR). Results: A total 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). Mean age was 42 years, 88% were female, and median observation period was 50.5 months. Renal prognosis was significantly different among the classes, and significantly poor in the patients with higher modified National Institute of Health (mNIH) Chronicity index (C index, ≥4) by a log-rank test (p=0.05, p=0.02 respectively). By Cox proportional hazard models, only C index was significantly associated with renal outcome (Hazard Ratio; 1.32, 95% CI; 1.11-1.56, p≤0.01), while the classes, the 2003 activity and chronicity subdivision, and mNIH activity index had no significant association with renal outcome. Each component of C index was significantly associated with renal outcome in different models. Conclusion: This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification

This report concerns a case of granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis (WG)) with bronchus narrowing. Although nasal biopsy had been performed three times, no positive histology for GPA (WG) could be obtained. Flexible bronchoscopy revealed diffuse erythema, edema of the mucosa and stenosis of the right mainstem bronchus. Transbronchial biopsy identified granuloma with giant cells. These findings led to a diagnosis of GPA (WG). This case suggests that biopsy from the bronchus is useful for diagnosis of GPA (WG).

Background Efficacy and toxicity of methotrexate (MTX) differs among individual patients, suggesting the influence of genetic variations in enzymes associated with MTX metabolism and folate metabolic pathway. Recent advances in pharmacogenetics (PGx) may permit the prediction of an individual patient’s response to MTX. Objectives In order to create a prediction model for adverse events of MTX, we investigated the polymorphisms relevant to the hepatotoxicity using the DMET microarray and direct-sequencing (DS) method for detection of 1,971 variants in enzymes concerned in drug-metabolism. Methods: Study subjects A total of 200 RA patients treated with MTX were retrospectively recruited from the Center for Rheumatic Diseases, Shinko Hospital, and 33 patients with hepatotoxicity (AST or ALT > 40 IU/L with MTX ≤ 8mg/week) were sorted. Roughly age- and sex-matched 38 patients without hepatotoxicity (AST and ALT ≤ 40 IU/L with MTX ≥ 8mg/week) were also selected. Genotyping DNA samples were extracted from whole blood samples. We used DMET Plus array (Affymetrix, Inc.) for genotyping 1,934 variants in 231 genes related to pharmacokinetics. Additionally, the other 37 variants in 17 genes, formerly reported to be associated with MTX efficacy or toxicity, were genotyped by DS method1, 2). Statistical analysis We firstly compared frequencies of genotypes in the two groups by Fisher’s exact test, and the variants with p<0.1 were included in construction of hepatotoxicity prediction model. Multiple logistic regression analysis was used to construct the model, which performance was evaluated by ROC analysis. Results Among 37 variants in 17 genes reported formerly to be associated with MTX efficacy/toxicity, only 2 SNPs in 2 enzymes (MTRR and ADORA2A) were shown to be significantly associated with hepatotoxicity (p<0.05). Next, frequency of genotypes in 1,971 variants of 246 genes for patients with and without hepatotoxicity was compared by Fisher’s exact test. 49 SNPs were extracted from a total of 1,971 variants with a significance level of p<0.1. Finally, multiple logistic regression analysis was used to construct the prediction model for hepatotoxicity. By stepwise selection procedure, we obtained a prediction model in whicha combination of 12 SNPs could discriminate patients between with and without hepatotoxicity. The ROC analysis showed an AUC of 0.9857 with 97.0% sensitivity and 89.5% specificity. Conclusions We found a combination of 12 SNPs in genes related to drug metabolism/transport that could predict hepatotoxicity of MTX with high sensitivity and specificity. After validation in other cohort, this model may lead to appropriate usage of MTX with PGx. References Ranganathan P, McLeod HL: Methotrexate Pharmacogenetics. The Fist Step toward Individualized Therapy in Rheumatoid Arthritis. Arthritis Rheum. 54:1366-1377, 2006. Wessels JAM, et al: A Clinical Pharmacogenetic Model to Predict the Efficacy of Methotrexate Monotherapy in Recent-Onset Rheumatoid Arthritis. Arthritis Rheum. 56:1765-1775, 2007. ...