Physician approval for pregnancy in patients with systemic lupus erythematosus showing only serological activity: A vignette survey study.

OBJECTIVE: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity. METHODS: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios. RESULTS: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months. CONCLUSIONS: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses.

Prognostic analysis of pulmonary hypertension with lung parenchymal lesion: Comparison of mortality with and without connective tissue disease.

BACKGROUND: The prognosis of pulmonary hypertension (PH) associated with connective tissue diseases related to interstitial pneumonia (CTD-IP PH) is relatively good among patients with PH and lung disease. However, the impact of pulmonary vasodilator treatment on the prognosis of CTD-IP PH compared with that of PH-induced chronic lung disease (group-3 PH) remains unclear. METHODS: From 2012 to 2022, 50 patients with lung parenchymal lesions diagnosed with PH (mean pulmonary arterial pressure >20 mmHg) at Juntendo University Hospital were divided into two groups: CTD-IP PH (30 patients) and group 3-PH (20 patients). The impact of pulmonary vasodilator treatment and the use of long-term oxygen therapy (LTOT) on the prognosis of each group was examined retrospectively. RESULTS: The prognosis of CTD-IP PH was significantly better compared to group-3 PH. While the treatment with pulmonary vasodilators did not affect the prognosis in group 3-PH, the prognosis of the patients treated with vasodilators in the CTD-IP PH group was significantly better than that of the non-treated patients. Treatment with multi-pulmonary vasodilators did not affect the prognosis in CTD-IP PH. Although the prognosis for the patients with LTOT was poor in all registered patients in the present study, treatment with pulmonary vasodilators improved the prognosis even under the use of LTOT in CTD-IP PH (P = 0.002). In a multivariate analysis of the CTD-IP PH group, pulmonary vasodilator treatment was an independent factor for better prognosis. CONCLUSION: Treatment with a pulmonary vasodilator for CTD-IP PH may improve the prognosis, even in patients requiring LTOT.

Critical role of lectin pathway mediated by MBL-associated serine proteases in complement activation for the pathogenesis in systemic lupus erythematosus.

In complement activation system, although the classical pathway has shown to play a critical role for the pathogenesis of SLE, the role of lectin pathway has remained unknown in the pathogenesis of SLE. As Mannose-binding lectin-associated serine proteases (MASPs) are associated with activation of the lectin pathway, we conducted this study to clarify MASPs associations in the pathogenesis of SLE. We evaluated the serum level of MASPs (MASP-1 and MASP-2) in total 68 SLE patients consisting of 15 patients with biopsy-confirmed membranous lupus nephritis (M-LN), 35 patients with biopsy-confirmed proliferative lupus nephritis (P-LN), and 18 SLE patients without LN (non-LN). Our data showed that the serum levels of MASPs were reduced in both P-LN and non-LN although those of M-LN were not reduced. Our data show that the lectin pathway mediated by MASPs plays a critical role for the pathogenesis of SLE except for M-LN.

Promoting awareness of terminology related to unmet medical needs in context of rheumatic diseases in Japan: a systematic review for evaluating unmet medical needs.

To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes.

Transitions in vascular ultrasonography findings of temporal arteritis in a GCA case with progressive temporal headache and visual impairment.

The European League Against Rheumatism and the American College of Rheumatology have stated that the halo sign on vascular ultrasonography (v-US) is relevant in diagnosing giant cell arteritis (GCA) and is equivalent to temporal artery biopsy. However, there are only a few reports about transitions in v-US findings after glucocorticoid (GC) therapy. We report the transitions in the v-US findings in a case of GCA after GC therapy. The patient had rapidly progressive symptoms, and there were concerns about blindness. After GC therapy, we first observed improvement in headache and visual impairment symptoms within 1 week, followed by rapid improvement in laboratory findings within 2 weeks. Subsequently, there were improvements in v-US findings after more than 2 months. In conclusion, these findings showed a dissociation between improvements in clinical symptoms and v-US findings of the temporal artery. Additionally, this case suggests that regular examination of v-US findings is useful in evaluating GCA with evident vascular wall thickness before GC therapy.

Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.

OBJECTIVE: Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. METHODS: Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin-sequencing. RESULTS: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRAhigh synovial fibroblasts, autoimmune-associated B cells, GZMK+ GZMB+ CD8+ T cells, interleukin (IL)1-ß+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)-α, interferons (IFNs), and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively. CONCLUSION: This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.

Autoantibodies in lupus nephritis useful in distinguishing proliferative nephritis from membranous nephritis.

OBJECTIVES: This study was conducted to determine autoantibodies associated with lupus nephritis (LN), especially those useful in diagnosing proliferative and membranous nephritis. METHODS: A total of 106 patients with LN and 63 patients with systemic lupus erythematosus but no nephritis were enrolled; then, 55 patients were selected from the LN group and were divided into two groups: proliferative nephritis patients (n = 36) and membranous nephritis patients (n = 19). The autoantibody profiles of patients' sera were evaluated using the EUROLINE ANA Profile 3 (IgG) kit. RESULTS: A higher positivity rate of anti-double-stranded DNA antibody and anti-histone antibody was seen in LN patients compared to nonrenal systemic lupus erythematosus patients. In comparing between proliferative and membranous nephritis, the positivity of anti-nucleosome antibody was higher in proliferative nephritis, although it was not statistically significant. However, anti-nucleosome antibody-positive patients with LN had a higher prevalence of haematuria and pyuria, which are strong indications of proliferative nephritis. Also, a significantly higher positivity rate of anti-RNP70 antibody was seen in membranous nephritis compared to proliferative nephritis. CONCLUSIONS: Our results showed that anti-nucleosome and anti-RNP70 antibodies may be predictive nonhistological factors for discriminating between proliferative and membranous LN.

Effect of Prophylactic Dose of Trimethoprim-Sulfamethoxazole on Serum Creatinine in Japanese Patients With Connective Tissue Diseases.

Objectives: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. Methods: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. Results: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (-0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. Conclusions: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL.

Periostin-related progression of different types of experimental pulmonary hypertension: A role for M2 macrophage and FGF-2 signalling.

BACKGROUND AND OBJECTIVE: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH. METHODS: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline-pyrrole (MCT-P) in wild-type (WT) and periostin-/- mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)-2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH-induced WT and periostin-/- mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated. RESULTS: In PH induced by SuHx and MCT-P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin-/- mice. PA remodelling post-SuHx treatment was also mild in periostin-/- mice compared to WT mice. Expression of macrophage-associated chemokines and FGF-2 in lung tissue, and accumulation of CD68-positive cells in the RV were less in SuHx periostin-/- than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor-ß. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls. CONCLUSION: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH.

Seroprevalence of anti-SARS-CoV-2 antibodies in Japanese COVID-19 patients.

OBJECTIVES: To determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients. METHODS: Serum samples (n = 114) from 34 COVID-19 patients with mild to critical clinical manifestations were examined. The presence and titers of IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were determined by a chemiluminescent microparticle immunoassay (CMIA) using Alinity i SARS-CoV-2 IgG and by an immunochromatographic (IC) IgM/IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test. RESULTS: IgG was detected by the CMIA in 40%, 88%, and 100% of samples collected within 1 week, 1-2 weeks, and 2 weeks after symptom onset in severe and critical cases, and 0%, 38%, and 100% in mild/moderate cases, respectively. In severe and critical cases, the positive IgG detection rate with the IC assay was 60% within one week and 63% between one and two weeks. In mild/moderate cases, the positive IgG rate was 17% within one week and 63% between one and two weeks; IgM was positive in 80% and 75% of severe and critical cases, and 42% and 88% of mild/moderate cases, respectively. On the CMIA, no anti-SARS-CoV-2 IgG antibodies were detected in COVID-19 outpatients with mild symptoms within 10 days from onset, whereas 50% of samples from severe inpatients were IgG-positive in the same period. The IC assay detected higher IgM positivity earlier from symptom onset in severe and critical cases than in mild/moderate cases. CONCLUSIONS: A serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.

Application of gamma radiation for disinfection of fungi in a large volume of historical archives damaged by flood following Typhoon Hagibis 2019, Japan: A case report.

A large volume of historical archives was extensively damaged by flood water, following Typhoon Hagibis in Fukushima, Japan, in October 2019. They were rescued from the stricken area within a week, however, the prolonged exposure of paper documents to water caused severe biodegradation by fungal growth. To disinfect fungi, the paper documents were exposed to gamma radiations emitted by a source of Cobalt 60 by the industrial irradiation service. The wet paper documents were mainly contaminated with hydrophilic and cellulolytic fungi, including Trichoderma, Stachybotrys, and Fusarium; no fungi grew after irradiation. These results indicated that the average absorbed dosage from 13.1 kGy to 16.1 kGy were sufficient to disinfect paper documents heavily contaminated with fungi. In the present study, we demonstrated the successful practical use of irradiation in fungi-damaged paper documents using a commercial gamma-irradiation facility.

Long-term treatment of pulmonary arterial hypertension with macitentan in Japanese patients.

Objective: Macitentan, a novel dual endothelin receptor antagonist, was approved for the treatment of pulmonary arterial hypertension (PAH) in Japan. However, long-term effects in Japanese patients of macitentan are currently unavailable. This study sought to assess the long-term efficacy and safety of macitentan in Japanese patients with PAH.Methods: In this multicenter, open-label, clinical extension study (JapicCTI-121986), efficacy was evaluated based on the change from baseline at 24, 48, 72, 96 and 120-week in the 6-minute walk distance (6MWD), World Health Organization (WHO) functional class, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. In addition, the time to a hospitalization related to PAH and a morbidity/mortality event was determined. As for safety, the incidence of adverse events and changes in laboratory data and vital signs were assessed.Results: Macitentan was administered at a once-daily dose of 10 mg in 30 PAH patients with a median treatment period of 2.4 years (range, 229-1037 days). The improvements in 6MWD, WHO functional class and NT-pro-BNP at week 24 were maintained throughout the long-term follow-up. Hospitalization related to PAH occurred in 2 patients. Levels of liver enzyme and hemoglobin remained unchanged throughout the study period.Conclusions: This study suggests that the long-term use of macitentan is well tolerated and effective in Japanese patients with PAH. We concluded that macitentan can be a possible approach to reduce morbidity/mortality in Japanese PAH patients.

Diagnosis of giant cell arteritis by head-contrast three-dimensional computed tomography angiography: two case reports.

INTRODUCTION: Temporal artery biopsy is essential for the diagnosis of giant cell arteritis. It has been shown that 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance angiography, and ultrasonography are useful for the diagnosis of giant cell arteritis. However, there are only a few reports on the usefulness of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. We describe two cases in which giant cell arteritis was difficult to diagnose using positron emission tomography-computed tomography and magnetic resonance angiography but was diagnosed using three-dimensional computed tomography angiography, thus showing the importance of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. CASE PRESENTATION: Case 1: An 81-year-old Japanese man. Laboratory investigations revealed normocytic anemia and raised inflammatory marker levels. Slight bleeding in the right posterior pole of his eyeball and leukoma of his left cornea were observed on fundus examination. Stenosis and stoppage of the temporal artery were detected on three-dimensional computed tomography angiography. A diagnosis of giant cell arteritis was made, and he was started on orally administered prednisolone. His headache and C-reactive protein levels improved. Four weeks after glucocorticoid steroid treatment, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery. Case 2: A 74-year-old Japanese woman. A dose of 20 mg of prednisolone was administered and her polymyalgia and polyarthritis improved; however, her headache and ear occlusion persisted. Although vasculitis was not detected on positron emission tomography-computed tomography, stenosis and stoppage of the temporal artery were detected on computed tomography angiography. She was diagnosed as having giant cell arteritis and started on orally administered prednisolone treatment (60 mg daily). Her headache and C-reactive protein levels improved. Four weeks after glucocorticoid treatment, three-dimensional computed tomography angiography showed improvement in stenosis and stoppage of temporal artery. CONCLUSIONS: In both patients with giant cell arteritis, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery after glucocorticoid treatment. We conclude that computed tomography angiography along with magnetic resonance angiography, positron emission tomography-computed tomography, and ultrasonography are important for the diagnosis of giant cell arteritis.

The Association of Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibodies in Patients With Rheumatoid Arthritis and Interstitial Lung Disease.

OBJECTIVES: This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. PATIENTS AND METHODS: We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. RESULTS: Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p<0.05). Levels of anti-threonyl-tRNA-synthetase (anti-PL-7) and anti-alanyl-tRNA-synthetase (anti-PL-12), two anti-ARS antibodies, were higher in RA patients with concurrent ILD (both p<0.05). Myositis and ILD worsening were not observed in three anti-ARS antibody- positive patients despite biological disease modifying antirheumatic drug administration. There was no difference in anti-cyclic citrullinated peptide and rheumatoid factor specificities between patients with or without ARS antibodies. CONCLUSION: Anti-ARS antibodies were detected in RA patients, with higher prevalence in patients with concurrent ILD. RA patients, specifically those with ILD complications, should be tested for anti-ARS antibodies.

A case of ankylosing spondylitis with concurrent Takayasu arteritis.

We herein report a case involving a 56-year-old man who had experienced neck and lower back pain since the age of 23 years. Ankylosing spondylitis (AS) was diagnosed at 41 years of age, and treatment with sulfasalazine was initiated. At 44 years of age, the patient developed respiratory distress on exertion and chest pain. Aortic regurgitation (AR) was diagnosed via echocardiography, and the patient presented to our hospital for close examination and treatment. Coronary computed tomography angiography revealed no lesions in the coronary artery; however, magnetic resonance angiography revealed stenotic lesions in the left common carotid artery and left subclavian artery. Based on the findings of a physical examination, fundus examination, and blood tests, the patient was diagnosed with AS with concurrent Takayasu arteritis (TA). Upon administration of steroids to alleviate inflammation caused by an autoimmune mechanism, the patient's chest symptoms and inflammatory findings improved. AR was treated with aortic valve replacement and prosthetic blood vessel replacement, after which the patient progressed well. Intraoperative aortic biopsy revealed findings pathologically consistent with TA. Although AS with concurrent AR is well described, AS with concurrent TA, as in the present case, is rare.

Predictive markers and prenatal management of isolated fetal complete atrioventricular block: A retrospective review at a single institution.

AIM: The study was conducted to determine an effective method for identifying patients at high risk of developing isolated complete atrioventricular block (CAVB) and to review the efficacy of prenatal anti-inflammatory treatment. METHODS: Fourteen CAVB cases and 76 anti-Ro-positive cases without CAVB were included in the study. Anti-Ro/La titers by double immunodiffusion and the prevalence of anti-52 kDa/60 kDa-Ro/48 kDa-La by Western blotting were compared between anti-Ro-positive women with and without CAVB. Outcomes of anti-Ro-positive CAVB cases were compared based on active prenatal anti-inflammatory treatment (plasma exchange or transplacental betamethasone). We evaluated the outcomes of five pregnancies from three women who had an affected child and underwent prophylactic plasma exchange (PEX) during subsequent pregnancy. RESULTS: Ten out of 14 patients with CAVB were positive for anti-Ro. Anti-Ro titers were significantly higher in patients with CAVB (CAVB median 64; without CAVB median 16; P < 0.01). All cases with CAVB showed high titers of anti-Ro (≥ 32×), whereas only 42% of cases without CAVB showed high titers (≥ 32×) (P < 0.001). The survival rate at one year was 80% in anti-Ro-positive CAVB cases with active prenatal anti-inflammatory treatment, but only 40% in cases that did not receive treatment. Recurrence was not observed in cases treated with prophylactic PEX. CONCLUSIONS: An anti-Ro level of 32× could be the threshold value for CAVB development. Prenatal anti-inflammatory treatment in patients with CAVB and prophylactic PEX in patients who had an affected child may have the potential to improve pregnancy outcomes.

Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody-positive inflammatory myositis.

Objective: The aim of this study was to evaluate the clinical characteristics of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive inflammatory myositis, and the change in anti-MDA5 antibody titres before and after onset. Method: For 105 PM/DM patients, newly diagnosed in our hospital within the period 2008-2016, serum anti-MDA5 antibody levels were measured at diagnosis and after treatment by ELISA using the MESACUP anti-MDA5 test. The relationships between anti-MDA5 antibody levels and clinical manifestations, laboratory data, and mortality were examined. Result: Compared with patients who were anti-MDA5 antibody negative, those who were antibody positive demonstrated more frequent dermatitis, clinically amyopathic DM, interstitial lung disease and rapid-progressive interstitial lung disease, as well as significantly higher serum ferritin, significantly lower creatine kinase and aldolase, and significantly less frequent ANA (⩾1:160) and anti-cytoplasmic pattern of ANA staining positivity. Anti-MDA5 antibody titres were examined before disease onset in two patients; one showed antibody positivity with low titres 2 years earlier, while both exhibited increased titres at onset. Anti-MDA5 antibody titres declined significantly less in survivors than in non-survivors after treatment; however, there was no significant difference between the two groups when the rate was compared at 2 months after treatment. Conclusion: An initial decrease in anti-MDA5 antibody titre after commencement of treatment was observed in most of the patients, including in fatal cases, suggesting that this may not necessarily be a useful marker for treatment of patients with DM.

Elevated serum levels of soluble CD146 in patients with systemic sclerosis.

CD146, a transmembrane glycoprotein member of the immunoglobulin superfamily, acts as an adhesion molecule that helps maintain the cell monolayer. Human endothelial cells expressing CD146 are involved in angiogenesis and inflammation. Recently, we developed a sandwich ELISA for detecting soluble CD146 (sCD146) in human serum specimens. The aim of this study is to determine serum levels of sCD146 in patients with systemic sclerosis (SSc) and to examine the relationship between sCD146 levels and clinical manifestations. We quantified serum sCD146 levels in 47 serum samples from patients fulfilling criteria for SSc, 23 serum samples from patients fulfilling criteria for rheumatoid arthritis (RA), and 25 healthy controls. We also investigated the relationship between sCD146 levels and various clinical characteristics with SSc patients. Levels of sCD146 were significantly higher in the 47 patients with SSc than in the 25 healthy controls and 23 patients with RA (12.50 vs. 6.91 vs. 9.95 ng/ml; p < 0.001). Serum sCD146 levels in SSc patients with pulmonary arterial hypertension (PAH) were lower than in SSc patients without PAH (10.12 vs.13.17 ng/ml; p < 0.01). The serum levels of sCD146 were elevated in patients with SSc. However, decreased sCD146 levels were observed in SSc patients with PAH. Further studies are necessary to elucidate the sources and the mechanisms.