Reconstruction of Sjögren's syndrome-like sialadenitis by a defined disease specific gut-reactive single TCR and an autoantibody.

Lymphocytes such as CD4+ T cells and B cells mainly infiltrate the salivary glands; however, the precise roles and targets of autoreactive T cells and autoantibodies in the pathogenesis of Sjögren's Syndrome (SS) remain unclear. This study was designed to clarify the role of autoreactive T cells and autoantibodies at the single-cell level involved in the development of sialadenitis. Infiltrated CD4+ T and B cells in the salivary glands of a mouse model resembling SS were single-cell-sorted, and their T cell receptor (TCR) and B cell receptor (BCR) sequences were analyzed. The predominant TCR and BCR clonotypes were reconstituted in vitro, and their pathogenicity was evaluated by transferring reconstituted TCR-expressing CD4+ T cells into Rag2-/- mice and administering recombinant IgG in vivo. The reconstitution of Th17 cells expressing TCR (#G) in Rag2-/- mice resulted in the infiltration of T cells into the salivary glands and development of sialadenitis, while an autoantibody (IgGr22) was observed to promote the proliferation of pathogenic T cells. IgGr22 specifically recognizes double-stranded RNA (dsRNA) and induces the activation of dendritic cells, thereby enhancing the expression of IFN signature and inflammatory genes. TCR#G recognizes antigens related to the gut microbiota. Antibiotic treatment severely reduces the activation of TCR#G-expressing Th17 cells and suppresses sialadenitis development. These data suggest that the anti-dsRNA antibodies and, TCR recognizing the gut microbiota involved in the development of sialadenitis like SS. Thus, our model provides a novel strategy for defining the roles of autoreactive TCR and autoantibodies in the development and pathogenesis of SS.

Combining dynamics of serum inflammatory and nutritional indicators as novel biomarkers in immune checkpoint inhibitor treatment of non-small-cell lung cancer with bone metastases.

OBJECTIVES: We aimed to investigate the association of the dynamics of serum inflammatory and nutritional indicators with immune checkpoint inhibitor (ICI) response in non-small-cell lung cancer (NSCLC) with bone metastases, and to develop a novel predictive scoring system based on these indicators. METHODS: Patients with NSCLC having bone metastases treated with ICIs were categorized as: the development cohort (January 2016 to March 2021, n = 60) and the validation cohort (April 2021 to June 2023, n = 40). Serum indicators of inflammation and nutrition such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), albumin, prognostic nutritional index (PNI) were investigated before and six weeks after ICI initiation. The correlations of these dynamics with bone metastasis response rate (BoMRR) and overall survival (OS) were analyzed. A scoring system consisting of independent predictors was developed (IMMUNO-SCORE) and correlations with clinical outcomes were validated using the validation cohort. RESULTS: In the development cohort, multivariable analysis showed that NLR and PNI dynamics and CRP, NLR, and PNI dynamics were independent predictors of BoMRR and OS, respectively. The IMMUNO-SCORE consisting of NLR and PNI dynamics, which were the common predictors of the clinical outcomes, was significantly correlated with BoMRR (p < 0.01) and OS (p < 0.001) in cross-validation. The area under the curve of the score (0.786) was higher than individual NLR and PNI dynamics (0.72 and 0.684). CONCLUSION: Dynamics in NLR and PNI were demonstrated as biomarkers of treatment response and prognosis in ICI treatment of NSCLC with bone metastases, and the score combining these biomarkers was significantly correlated with clinical outcomes.

Clinical importance of anti-Ro52 antibody for polymyositis and dermatomyositis.

OBJECTIVES: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM). PATIENTS AND METHODS: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups. RESULTS: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups. CONCLUSION: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM.

The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma.

Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo-not reached; n = 39) and 23.7 months (95% CI: 14.5-43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29-0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Genomic evolutional analysis of surgical resected specimen to assess osimertinib as a first-line therapy in two patients with lung cancer harboring EGFR mutation: Case series.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is crucial for patients with lung cancer harboring EGFR mutations. However, almost all patients experience disease progression, regardless of their response to the targeted therapy, necessitating the development of additional treatment options. Two patients with lung cancer harboring EGFR-L858R mutations in exon 21 were treated by surgical resection during successful osimertinib treatment. Because the pathological diagnosis was suspected to be pleural metastasis, osimertinib treatment was continued until disease progression. We analyzed the evolution of genomic alterations and the levels of AXL using tumor specimens obtained by repeated biopsies during the course of treatment: initial diagnosis, operation, and disease progression. Genetic alterations detected at the three time points were dramatically changed and showed reductions in numbers, while EGFR-L858R mutations were detected in all samples tested in both patients. Immunohistochemical expression of AXL remained positive from the beginning of analysis to disease progression. Clonal evolution under oncogenesis is related to gradual accumulation of genomic alterations during tumor growth. However, our case series revealed that volume reduction procedures may cause this phenomenon. Therefore, identification of intrinsic drug-resistant cells in tumors may be as important as detection of acquired genetic alterations.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

Role of inter-alpha-trypsin inhibitor heavy chain 4 and its citrullinated form in experimental arthritis murine models.

Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) is a major protein in serum and reported to be upregulated at the onset of rheumatoid arthritis (RA). Its citrullinated form, cit-ITIH4, is specifically found in the serum and synovial fluid of patients with RA. However, the detailed function of ITIH4 in arthritis remains unknown. The aim of this study was to clarify the role of ITIH4 and cit-ITIH4 using experimental arthritis models. ITIH4 and cit-ITIH4 expression was examined in steady-state mice and two different arthritis models, and their pathological effects were examined in Itih4-deficient mice. In naïve C57BL/6 (WT) mice, ITIH4 was expressed as mRNA in the liver and the lung and was expressed as protein in serum and hepatocytes. In K/BxN serum transferred arthritis (K/BxN-STA) and collagen-induced arthritis (CIA), ITIH4 and cit-ITIH4 in sera were increased before the onset of arthritis, and cit-ITIH4 was further increased at the peak of arthritis. In Itih4-deficient mice, citrullinated proteins in serum and joints, especially 120 kDa protein, were clearly diminished; however, there was no significant difference in arthritis severity between WT and itih-/- mice either in the K/BxN-STA or CIA model. CIA mice also exhibited pulmonary lesions and itih4-/- mice tended to show enhanced inflammatory cell aggregation compared to WT mice. Neutrophils in the lungs of itih4-/- mice were significantly increased compared to WT mice. In summary, ITIH4 itself did not alter the severity of arthritis but may inhibit autoimmune inflammation via suppression of neutrophil recruitment.

Multidrug-resistant IgA Vasculitis with Gastrointestinal Symptoms Successfully Treated with Intravenous Cyclophosphamide and Maintained with Mycophenolate Mofetil.

We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.

Benign endobronchial lipoma causing repeated pneumonia.

Endobronchial lipomas are rare; nonetheless, physicians should consider them as a differential diagnosis in patients with repeated pneumonia. Computed tomography and bronchoscopy are recommended for diagnosis. In this case, the patient's cough was ameliorated after undergoing a right basal segmentectomy.

Long-term outcome of patients with peripheral ground-glass opacity-dominant lung cancer after sublobar resections.

OBJECTIVE: This study aimed to evaluate the long-term prognosis of patients with peripheral small ground-glass opacity-dominant lung cancer after sublobar resection. We have already reported the 5-year safety and efficacy of sublobar resection and report the long-term outcomes after a 10-year follow-up period. METHODS: Between May 2009 and April 2011, 333 patients with radiologically noninvasive peripheral lung cancer were enrolled from 51 institutions (median age, 62 years at registration) and followed up until May 6, 2021. Of these patients, sublobar resections with wedge resection as the first choice were performed in 314 patients (258 wedge resections and 56 segmentectomies), conversion lobectomies were performed in 11 patients, and 8 patients were ineligible. RESULTS: The 10-year relapse-free survival and overall survival for the 314 patients with sublobar resections were 98.6% (95% confidence interval, 96.2-99.5) and 98.5% (95% confidence interval, 96.1-99.4), respectively. There was 1 local recurrence at the resection margin. Among the patients, second cancers were observed in 43 patients (13.4%; 95% confidence interval, 9.8-17.6), of which 18 were second lung cancers (5.8%; 95% confidence interval, 3.5-8.9). CONCLUSIONS: Peripheral ground-glass opacity-dominant lung cancer is cured by sublobar resection, with wedge resection as the first choice, and the indications for other treatment options should be further investigated. The incidence of second cancer is similar to that in the general Japanese population.

[Left Metastatic Lung Tumor for a Patient with Scimitar Syndrome:Report of a Case].

Scimitar syndrome is a subtype of partial anomalous pulmonary venous connection, a rare congenital disorder associated with hypoplasia of the right lung. In addition to the difficulty of isolated lung ventilation, resection of the left lung is associated with the risk of developing right heart failure due to increased right-to-left shunts. We report a case of a left lung metastasis of a patient with scimitar syndrome. The patient, a 58-year-old male, was diagnosed with scimitar syndrome at the age of 26 but had never experienced any symptoms. He underwent chemoradiotherapy for mid-pharynx carcinoma and achieved complete response. During follow-up, a nodule appeared in the lower lobe of the left lung. Since right heart catheterization revealed a pulmonary blood flow/systemic blood flow ratio (Qp/Qs) ratio of 2.6, intra-cardiac blood flow was diverted prior to pulmonary resection. Stanford type A acute aortic dissection occurred intra-operatively, and total aortic arch replacement was performed. Three months later, partial pulmonary resection was performed with extracorporeal membrane oxygenation (ECMO) on standby. As oxygenation was maintained by placing a blocker in the left lower lobe bronchus and ventilating the left upper lobe with high frequency jet ventilation, the operation was completed without using ECMO. The nodule was pathologically diagnosed as metastasis of mid-pharynx carcinoma. He did not develop heart failure and was discharged on post operated day 15.

Genetic dissection of HLA-DRB1*15:01 and XL9 region variants in Japanese patients with systemic lupus erythematosus: primary role for HLA-DRB1*15:01.

OBJECTIVE: Major histocompatibility complex strongly contributes to susceptibility to systemic lupus erythematosus (SLE). In the European populations, HLA-DRB1*03:01 and DRB1*15:01 are susceptibility alleles, but C4 locus was reported to account for the association of DRB1*03:01. With respect to DRB1*15:01, strong linkage disequilibrium with a variant rs2105898T in the XL9 region, located between DRB1 and DQA1 and regulates HLA-class II expression levels, was reported; however, the causative allele remains to be determined. Leveraging the genetic background of the Japanese population, where DRB1*15:01 and DRB1*15:02 are commonly present and only DRB1*15:01 is associated with SLE, this study aimed to distinguish the genetic contribution of DRB1*15:01 and XL9 variants. METHODS: Among the XL9 variants, two (rs2105898 and rs9271593) previously associated variants in the European populations and two (rs9271375 and rs9271378) which showed a trend towards association in a Japanese Genome-Wide Association Study were selected. Associations of the XL9 variants and HLA-DRB1 were examined in 442 Japanese SLE patients and 779 controls. Genotyping of the XL9 variants was performed by TaqMan SNP Genotyping Assay and direct sequencing. HLA-DRB1 alleles were determined by PCR-reverse sequence-specific oligonucleotide probes. RESULTS: Among the XL9 variants, associations of rs2105898T and rs9271593C were replicated in the Japanese population. However, these associations became no longer significant when conditioned on DRB1*15:01. In contrast, the association of DRB1*15:01 remained significant after conditioning on the XL9 variants. CONCLUSION: In the Japanese population, HLA-DRB1*15:01 was found to be primarily associated with SLE, and to account for the apparent association of XL9 region.

Preoperative assessment of pleural adhesions in patients with lung cancer based on quantitative motion analysis with dynamic chest radiography: A retrospective study.

PURPOSE: Preoperative assessment of pleural adhesion is crucial for appropriate surgical planning. This study aimed to quantitatively evaluate the usefulness of motion analysis using dynamic chest radiography (DCR) for assessing pleural adhesions. METHODS: Sequential chest radiographs of 146 lung cancer patients with or without pleural adhesions (n = 25/121) were obtained using a DCR system during respiration (registration number: 1729). The local motion vector was measured, and the percentage of poor motion area to the maximum expiration lung area (%lung area with poor motion) was calculated. Subsequently, percentage values ≥49.0% were considered to indicate pleural adhesions. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the prediction performance. The percentage of lung area with poor motion was compared between patients with and without pleural adhesions (p < 0.05). RESULTS: DCR-based motion analysis correctly predicted pleural adhesions in 21 out of 25 patients, with 47 false-positive results (sensitivity, 84.0%; specificity, 61.2%; PPV, 30.9%; NPV, 94.9%). The lung with pleural adhesions showed a significantly greater %lung area with poor motion than the opposite lung in the same patient, similar to the cancerous lung in patients without pleural adhesions. CONCLUSION: On DCR-based motion analysis, pleural adhesions could be indicated by an increase in the percentage of lung area with poor motion. Although the proposed method cannot identify the exact location of pleural adhesions, information regarding the presence or absence of pleural adhesions provided by DCR would help surgeons prepare for challenging surgeries and obtain informed consent from patients.

Investigation of time profile of FEV1 across the onset of potential COPD: a retrospective cohort study using medical checkup data in Japan.

This study compared the time profile of FEV1 after COPD diagnosis among rapid decliners, slow decliners, and sustainers in the year of COPD diagnosis. COPD subjects were identified from the annual medical checkup records of Hitachi, Ltd., employees in Japan (April 1998-March 2019). Subjects were categorized into 3 groups (rapid decliner [decrease of FEV1 ≥ 63 mL/year], slow decliner [< 63 and ≥ 31 mL/year], and sustainer [< 31 mL/year]) for 5 years. The time profile of FEV1 was compared using mixed-effects model for 5 years after diagnosis; risk factors of rapid decliner were detected using logistic model/gradient boosting decision tree. Of 1294 eligible subjects, 18.6%, 25.7%, and 55.7% were classified as rapid decliners, slow decliners, and sustainers, respectively. The annual rates of FEV1 decline were similar 3 years before and until COPD diagnosis. The mean FEV1 in rapid decliners was 2.82 ± 0.04 L in year 0 and 2.41 ± 0.05 L in year 5, and in sustainers, it was 2.67 ± 0.02 L and 2.72 ± 0.02 L (year 0, p = 0.0004). In conclusion, FEV1 declined yearly before diagnosis and the time profiles of FEV1 were different in the 3 groups after COPD diagnosis. Therefore, appropriate treatment of the 3 groups with regular lung function tests is necessary to follow FEV1 decline after COPD onset.

Novel predictors of immune checkpoint inhibitor response and prognosis in advanced non-small-cell lung cancer with bone metastasis.

BACKGROUNDS: Immune checkpoint inhibitors (ICIs) can significantly prolong the survival of patients with advanced non-small-cell lung cancer (NSCLC); however, few studies on the therapeutic effects of ICIs on bone metastases were performed. METHODS: This retrospective study aimed to investigate the therapeutic effects of ICIs and determine predictors of favorable ICI response and prognosis in 55 advanced NSCLC patients with bone metastases who initiated ICI treatment between 2016 and 2019, with a mean follow-up period of 23.2 months. Patients were classified into responders (complete or partial response) and non-responders (stable or progressive disease) according to the MD Anderson Cancer Center (MDA) criteria, and the predictors of therapeutic response were identified using multivariate logistic regression analysis. Furthermore, overall survival from the time of ICI administration to the final follow-up or death was evaluated, and prognostic predictors were identified using Cox proportional hazards regression analysis. RESULTS: ICI response rate was 30.9% (complete in three cases, partial in 14). Median survival time was 9.3 months, with 1-year and 2-year survival rates of 40.6% and 19.3%, respectively. Responders survived significantly longer than non-responders (p = 0.03). Based on the receiver operating characteristic curve, the predictive cutoff value of the pretreatment neutrophil-to-lymphocyte ratio (NLR) was 2.1. Multivariate analysis identified female sex (p = 0.03), use of ICIs as first-line therapy (p < 0.01), and NLR <2.1 (p = 0.03) as significant predictors of therapeutic response, whereas concomitant use of a bone-modifying agent (p < 0.01), Katagiri score ≤6 points (p < 0.01), and NLR <2.1 (p = 0.02) were identified as significant predictors of good prognosis. CONCLUSIONS: This study identified some novel predictors for favorable therapeutic response and prognosis in advanced NSCLC patients with bone metastases undergoing ICI treatment. Pretreatment NLR less than 2.1 can be considered the most important predictor.

Diagnostic approach for mediastinal masses with radiopathological correlation.

PURPOSE: Mediastinal masses have various histopathological and radiological findings. Although lymphoma is the most common type of tumor, thymic epithelial and neurogenic tumors are common in adults and children, respectively, but several other types are difficult to distinguish. No previous review has simply and clearly shown how to differentiate mediastinal masses. METHOD: We conducted a review of the latest mediastinal classifications and mass differentiation methods, with a focus on neoplastic lesions. Both older and recent studies were searched, and imaging and histopathological findings of mediastinal masses were reviewed. Original simple-to-use differentiation flowcharts are presented. RESULTS: Assessing localizations and internal characteristics is very important for mediastinal mass differentiation. The mass location and affected organ/tissue should be accurately assessed first, followed by more qualitative diagnosis, and optimization of the treatment strategy. In 2014, the International Thymic Malignancy Interest Group presented a new mediastinal clinical classification. In this classification, mediastinal masses are categorized into three groups according to location: prevascular (anterior)-, visceral (middle)-, and paravertebral (posterior)-compartment masses. Then, the internal characteristics and functional images are evaluated. CONCLUSIONS: Differentiation of mediastinal masses is very difficult. However, if typical imaging findings and clinical characteristics are combined, reasonable differentiation is possible. In each patient, proper differential diagnosis may contribute to better treatment selection.

[Ingenuity for the Uniportal Video-assisted Thoracic Surgery as a Minimally Invasive Procedure].

Uniportal video-assisted thoracic surgery (VATS) is a minimally invasive, wound-reducing approach performed mainly in Europe and Asia. This approach is rapidly gaining popularity in Japan. We performed a technique with layer awareness, grasping and dissection of tissue membrane even in uniport VATS as for open thoracotomy or multiport VATS. Interference is a problem with uniport VATS because surgical instruments are inserted and removed through a small incision of 4 cm or less;there-fore, instrument selection is critical. The use of curved forceps ensures more working space and reduced interference. The incision should be placed between the 4th or 5th intercostal space and should be 3.5 cm in size at our institution. For vascular manipulation, ligation and transection can be used when it is difficult to divide vessels with a stapler. During mediastinal lymph node dissection, a precise view can be achieved with the use of a custom-made spatula. Uniport VATS was performed in 51 cases from January 2019 to June 2022. Although recurrence was observed in two cases, no serious perioperative complications were observed, and the procedures were performed safely.

Effect of climatic environment on immunological features of rheumatoid arthritis.

The aim of this study was to clarify the effect of climatic environment on the immunological features of rheumatoid arthritis (RA). Blood samples were collected from patients with RA and healthy controls (HCs), matched by age and sex, living in two locations, Tsukuba and Karuizawa, which differ in their altitude and average air temperature and atmospheric pressure. Analysis of peripheral blood mononuclear cells (PBMCs) revealed that the proportion of T and B cell subpopulations in HCs and RA patients were significantly different between two sites. Inverse probability weighting adjustment with propensity scores was used to control for potential confounding factors. The results revealed that, in comparison with RA patients in Tsukuba, those in Karuizawa showed a significant increase in cTh1, cTfh1, and Tph cells, and significant decrease in cTh17, cTh17.1, and CD8+ Treg in T cell subpopulations, and a significant increase in DNB, DN1, DN2, and class-switched memory B cells, and a significant decrease in unswitched memory B, naïve B cells, and ABCs in B cell subpopulations. Our results suggest the possibility that climatic environment might have an effect on immune cell proportion and function, and be related to the pathogenic mechanism of RA.

Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren's syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren's Syndrome Endocrinopathy) and ROSE II trials.

OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

OBJECTIVES: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). METHODS: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. RESULTS: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. CONCLUSIONS: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.