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Background Although there is increasing use of 18F-FDG PET/CT in the diagnostic procedure for IgG4-related disease (IgG4-RD), little is known about the quantification of 18F-FDG PET/CT. We aimed to evaluate the utility of the quantification of 18F-FDG PET/CT in the diagnosis of IgG4-RD by analyzing the relation between 18F-FDG PET/CT findings and histopathologic findings. Methods Twenty-one patients with IgG4-RD, in whom 18F-FDG PET/CT was performed at the time of diagnosis between November 2011 and July 2018, were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardized uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. Results The mean age at diagnosis was 64.6 ± 11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue than those in the histopathology-negative tissue (4.98 and 3.54, respectively P mean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively P mean to determine which of multiple lesions should be biopsied, a receiver operating characteristic (ROC) curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver = 1.66 as a cut-off value that could discriminate IgG4-RD-related lesions. Conclusions Our present study suggested that quantitative analysis of 18FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.

This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments.This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups.All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders.Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.

Introduction The low frequency of ectopic germinal center in labial salivary glands of patients with human T‐cell leukemia virus type 1 (HTLV‐1) antibody‐positive Sjögren's syndrome (SS) suggests that HTLV‐1 has some effects on follicular dendritic cells (FDCs). Methods We used flow cytometry, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) to investigate the direct effect of HTLV‐1 on B‐cell activating factors produced by established FDC like cells obtained from excised human tonsils. We then measured the serum B‐cell activating factor (BAFF) and C‐X‐C motif ligand (CXCL) 13 concentrations of the HTLV‐1‐seropositive SS patients and the HTLV‐1‐seronegative SS patients by ELISA. Results Among the 31 isolated specimens, 22 showed morphological characteristics of FDCs. Day 2‐cultured specimens showed expressions of CD14, CD23, CD40, intracellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1. After 2 weeks, 12 of these specimens expressed ICAM‐1, FDC, and fibroblast cell marker. Intracellular BAFF and CXCL13 were constitutively expressed regardless of stimulation. After direct coculture with the HTLV‐1‐infected T‐cell line HCT‐5 or MT‐2, the BAFF and CXCL13 expressions on the FDC‐like cells were decreased in accord with the increased number of HCT‐5 and MT‐2 cells with styliform change and without HTLV‐1 Gag protein expression. Interferons upregulated the concentration of BAFF (but not CXCL13) in the culture supernatant, which showed a declining trend under the presence of HCT‐5 or MT‐2. The serum concentrations of BAFF and CXCL13 in the HTLV‐1‐seropositive SS patients were lower than those of the HTLV‐1 seronegative SS patients. Conclusions HTLV‐1 partially inhibited the BAFF and CXCL13 expressions of established FDC‐like cells., Graphical abstract Expression of B‐cell activating factor (BAFF) was upregulated by addition of interferons. Although BAFF expression was inhibited by addition of human T‐cell leukemia virus type 1 infected cell line, HCT‐5 and MT‐2, the level was not inhibited by addition of control cell line, MOLT‐4.

The aim of our study was to analyze the expressions of nuclear factor of activated T cells (NFAT)-related substances including long noncoding RNA NRON which participates in pathophysiology of Sjögren’s syndrome (SS), and to assess the histologic findings in individuals with SS. In this study, the expressions of NRON, NFATc1, CD3/CD4, and proviral integration site for Moloney murine leukemia virus (PIM)-1 were examined by in situ hybridization, immunohistochemical analysis, and immunofluorescence in labial salivary glands (LSGs) obtained from 16 patients with SS and five controls. The microcell count method has been applied to calculate the NFATc1-positive area/infiltrating cell area in LSGs, and we compared those results to the infiltrating cell area, focus score, serum immunoglobulin G, and the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index. The NRON expression in the nuclei of cell-infiltration lesions of the SS patients were prominent. The NFATc1 expression was strong in the cytoplasm of infiltrating mononuclear cells and weak in ducts of both SS and controls. In SS, the NFATc1-positive area/infiltrating cell area was positively correlated with the infiltrating cell area and focus score. CD3/CD4 was expressed in infiltrating mononuclear cells, and PIM-1 colocalized with NFATc1 in the cytoplasm. These results suggest NRON along with NFATc1/PIM-1 in SS LSGs might participate in SS pathophysiology., Applied immunohistochemistry & molecular morphology, 29(10), pp. 734-740; 2021

Background: The relationship between anti-Ro52/SS-A antibody (anti-Ro52) and the clinical manifestations of Sjögren's syndrome (SS) has not been fully clarified. We determined the clinical factors relevant to SS patients with anti-Ro52. Methods: We conducted a retrospective study of 149 subjects suspicious for SS and 50 healthy control subjects. We analyzed items of the American-European Consensus Group (AECG) criteria and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results: SS was documented in 115 subjects. Anti-Ro52 was observed in 70 SS patients. Anti-Ro52 positivity showed a significantly higher association with anti-Ro60 positivity than with anti-centromere antibody (ACA) positivity (p < 0.05). Regarding the difference in the anti-Ro52 concentration, we observed six significantly relevant components: two AECG components and four non-AECG components. The anti-Ro52 concentration well-discriminated three clinical factors (ROC AUC >0.75), i.e., ACA seropositivity, ESSDAI score ≥1, and RF, and it moderately discriminated high serum IgG, focus score ≥1, and anti-La/SS-B antibody seropositivity (ROC AUC >0.7). A linear relationship between the ESSDAI score and the anti-Ro52 concentration was observed. Conclusion: A significant association between clinical factors (including the ESSDAI) and the anti-Ro52 concentration were revealed. Anti-Ro52 was more highly associated with anti-Ro60 positivity than with ACA positivity.

Rationale: Eosinophilic granulomatosis with polyangiitis (EGPA) is belongs to the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) subgroups. EGPA, unlike other subgroups of AAV, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis, has the unique feature that both ANCA and eosinophilic inflammation are involved in its pathogenesis. Although AAV often relapses, there are currently no reports of EGPA developing during other subgroups of AAV. Herein, we document a case of EGPA that developed during the clinical course of MPA. Patient concerns: A 61-year-old Japanese woman was diagnosed with MPA based on interstitial lung disease and myeloperoxidase-ANCA positivity. After starting immunosuppression therapy, including prednisolone and tacrolimus, she was expected to achieve clinical remission. Nonetheless, she occasionally experienced MPA relapse, which required an increased prednisolone dose, rituximab, intravenous cyclophosphamide, and plasma exchange. Three years after MPA onset, she developed renal amyloidosis; thus, subcutaneous tocilizumab was added to her regimen. Following clinical remission, the administration interval of her subcutaneous tocilizumab therapy was extended and immunosuppressants were discontinued. She then developed bronchial asthma and mild eosinophilia (eosinophilic count: ~1000/μL). Further, a year later, she underwent total hip replacement using a titanium implant. Subsequently, she developed abnormal sensation in both hands, numbness, and muscle weakness, as well as palpable purpura and massive eosinophilia (eosinophilic count: ~8500/μL). Diagnosis: We diagnosed the patient with EGPA based on 5 items (asthma, multiple mononeuropathies, sinus abnormality, and extravascular eosinophils) of the 1990 American College of Rheumatology classification criteria. Interventions: We administered 400 mg/kg intravenous immunoglobulin for 5 consecutive days, 300 mg mepolizumab subcutaneously every 4 weeks, and 40 mg/day prednisolone following pulsed methylprednisolone therapy (1000 mg/day for 3 consecutive days). Outcomes: After these treatments, the patient’s symptoms improved, and eosinophilic count and inflammatory markers declined. Lessons: The present case suggests that EGPA can be induced by the development of eosinophilic inflammation in other subgroups of AAV. Abbreviations: AAV = ANCA-associated vasculitis, ANCA = antineutrophil cytoplasmic autoantibody, CCL = chemokine (C–C motif) ligands, CRP = C-reactive protein, EGPA = eosinophilic granulomatosis with polyangiitis, IL = interleukin, ILC2 = group 2 innate lymphoid cells, ILD = interstitial lung disease, MPA = microscopic polyangiitis, MPO = myeloperoxidase, mPSL = methylprednisolone, PSL = prednisolone, TAC = tacrolimus, TCZ = tocilizumab, Th2 = T helper 2., Medicine, 101(44), art. no. e31401; 2022

Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. Methods: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. Results: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings., Arthritis Research and Therapy, 23, art. no. 197; 2021

Background: Relationship between anti-Ro52/SS-A antibody (anti-Ro52) and clinical manifestation of Sjögren's syndrome (SS) was sporadically described regarding involvement of internal organs.Objectives: To determine the clinical factors relevant to anti-Ro52 with SS.Methods: We conducted a retrospective study of subjects with suspected SS (n=149), patients with rheumatoid arthritis (RA) (n=62), and healthy subjects (n=50). We analyzed components of the American-European Consensus Group (AECG) criteria, Raynaud's phenomenon (RP), anti-centromere antibody (ACA), serum IgG, rheumatoid factor, and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).Results: Among the 149 suspected SS subjects, 115 subjects were classified as having SS. Anti-Ro52 was observed in 70 SS patients (60.9%), of whom 31 patients had markedly elevated anti-Ro52 (>500 U/ml). In the SS group, three patients with anti-Ro60−/anti-Ro52+ and 17 patients without anti-Ro were observed. Compared to ACA, the relevance of positive anti-Ro52 toward positive anti-Ro60 was significantly higher (p0.75) for ACA seropositivity, ESSDAI score ≥1, and RF or moderately high serum IgG, focus score ≥1, and anti-La/SS-B antibody seropositivity (ROC AUC >0.7). A linear relationship between the ESSDAI score and anti-Ro52 was observed.Conclusion: Significant relevance between anti-Ro52 and anti-Ro60 as well as significant items including the ESSDAI regarding the anti-Ro52 concentration was revealed. Regarding relevance toward anti-Ro60, anti-Ro52 had a higher association than ACA.(246/250 words)

Background:Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, which results in reduced secretory functions and oral and ocular dryness (1). In addition, patients often have extraglandular manifestations, such as interstitial pneumonia and interstitial nephritis, and the appearance of autoantibodies such as anti-Ro/SS-A and La/SS-B antibodies. Salivary gland ultrasonography (SGUS) is typically used to evaluate the findings of salivary glands; thus, we can evaluate the severity of salivary gland disorders due to SS using SGUS in real time (2).Objectives:To identify clinical indices, including disease activity, associated with glandular involvement evaluated using SGUS in patients with SS.Methods:We enrolled patients with SS (n=115) and non-SS sicca subjects (n=90) who visited Nagasaki University Hospital between 1995 and 2019. The patients’ SS classifications were based on the 2002 American–European Consensus Group (AECG) SS classification criteria (3). The non-SS sicca subjects exhibited sicca symptoms but did not fulfill the AECG SS classification criteria. SGUS and clinical indices such as age, sex, the focus score (FS), sicca symptoms, the Saxon test results, Schirmer’s test results, anti-SS-A/Ro antibody positivity, anti-SS-B/La antibody positivity, anti-centromere antibody (ACA) positivity, serum immunoglobulin G levels, and the clinical European League Against Rheumatism SS disease activity index were examined. The ultrasonography (US) score was calculated based on SGUS imaging (hypoechoic area, hyperechoic band, and irregular border) (4).Results:The US score was significantly higher in patients with SS than that in non-SS sicca subjects. In addition, we found significant correlations between the US score and FS in patients with SS. Multivariate analysis revealed the FS, Saxon test positivity, and ACA positivity as the variables independently associated with the US score in patients with SS. These results were the same in the primary SS patient group (n=96). Patients with ACA positivity had significantly higher US scores compared to those in patients with ACA negativity, whereas the FS was not significantly high. In addition, patients with ACA positivity had significantly greater positivity of hyperechoic bands than that in patients with ACA negativity.Conclusion:This study indicated that ACA positivity, which is not reflected in sialadenitis of SS, is associated with the US score in patients with SS. These results suggest that US findings of patients with ACA positivity might show specific changes in salivary glands, such as fibrosis, and not only sialadenitis (5).References:[1]Ramos-Casals M, Tzioufas AG, Font J. Primary Sjogren’s syndrome: new clinical and therapeutic concepts. Ann Rheum Dis. 2005;64(3):347-54.[2]van Ginkel MS, Glaudemans A, van der Vegt B, Mossel E, Kroese FGM, Bootsma H, et al. Imaging in Primary Sjogren’s Syndrome. J Clin Med. 2020;9(8).[3]Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554-8.[4]Takagi Y, Nakamura H, Sumi M, Shimizu T, Hirai Y, Horai Y, et al. Combined classification system based on ACR/EULAR and ultrasonographic scores for improving the diagnosis of Sjogren’s syndrome. PLoS One. 2018;13(4):e0195113.[5]Nakamura H, Kawakami A, Hayashi T, Iwamoto N, Okada A, Tamai M, et al. Anti-centromere antibody-seropositive Sjögren’s syndrome differs from conventional subgroup in clinical and pathological study. BMC Musculoskelet Disord. 2010;11:140.Disclosure of Interests:None declared