Influences of advanced age in rheumatoid arthritis: A multicentre ultrasonography cohort study.

OBJECTIVES: We aimed to evaluate the effects of age on clinical characteristics and outcomes in biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD)-naïve patients with rheumatoid arthritis (RA). METHODS: We analysed the cases of 234 Japanese b/tsDMARD-naïve RA patients who underwent b/tsDMARD treatment in a multicentre ultrasound prospective observational cohort. We compared the clinical characteristics at baseline and outcomes at 12 months between those aged ≥60 years and those <60 years. RESULTS: Compared to the <60-year-old group (n = 78), the ≥60-year-old group (n = 156) had higher inflammatory marker values and ultrasound combined scores, especially wrist joints, at baseline. Age at baseline positively correlated significantly with the ultrasound scores at baseline; however, age was not a significant variable by the multiple regression analysis. The patients treated with different MOAs in the ≥60-year-old group had comparable outcomes and multiple regression analysis revealed that mechanism of action (MOA) was not a significant contributor to the Clinical Disease Activity Index at 12 months. CONCLUSIONS: RA patients with advanced age demonstrated distinctive clinical characteristics. The MOAs were not associated with clinical outcomes and ultrasound outcomes in RA patients with advanced age.

Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis.

OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.

Comparison of the quantitative measurement of 18F-FDG PET/CT and histopathological findings in IgG4-related disease.

OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised 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 (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-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.

Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.

BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.

Effectiveness and safety of non-tumor necrosis factor inhibitor therapy for anti-human T-cell leukemia virus type 1 antibody-positive rheumatoid arthritis.

OBJECTIVES: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. METHODS: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. RESULTS: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. CONCLUSION: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.

Diagnostic efficacy of ultrasound detection of enthesitis in peripheral spondyloarthritis.

Objective: We investigated the diagnostic efficacy of power Doppler ultrasound (PDUS) to detect enthesitis in Japanese patients with peripheral spondyloarthritis (SpA).Methods: This was a single-center cohort study of patients with peripheral symptoms suggestive of SpA. Articular synovia, tendons, and entheses were assessed by PDUS at baseline. Clinical, laboratory, and radiologic findings and classification criteria for SpA were also evaluated.Results: 136 patients were consecutively evaluated. A definite diagnosis was obtained in 111 patients, including 72 with SpA and 39 non-SpA. Among the patients with SpA, PDUS demonstrated articular synovitis in 40 of the 72 patients (56%), tenosynovitis or peritendinitis in 48 (67%), and enthesitis in 63 (88%). Considering PDUS alone, enthesitis in at least one site was the most useful means of differentiating SpA from non-SpA (sensitivity 87.5%; specificity 82.1%; accuracy 85.6%; positive likelihood ratio 4.88). Combining that finding along with fulfillment of Amor, European Spondyloarthropathy Study Group, or Assessment of SpondyloArthritis international Society criteria for peripheral SpA increased the specificity of the diagnosis (92.5%, 92.3%, and 97.4%, respectively).Conclusion: PDUS enthesitis is useful for the diagnosis of SpA with peripheral symptoms. Combining PDUS enthesitis with established SpA classification criteria is beneficial in diagnosing peripheral SpA.

[Comparison of Detectability for the New Image Processing and Conventional Image Processing by ROC Analysis: A Phantom Study of Chest Radiography].

The purpose of this study is to compare the detectability of diseases the new image processing and the conventional image processing by receiver operating characteristic (ROC) analysis and to show the usefulness of the new image processing. Radiographs with and without nodular cancer models in the chest phantom were used for observation samples. Totally 200 radiographs were evaluated by 10 radiological technologists (each readers had over 20 years or under 4 years of experience). The mean area under the curve (AUC) calculated from the over 20 years group was 0.754 for the new processing and 0.771 for the conventional processing (p value=0.651, 95% confidence interval=-0.084/0.049 (lower bound/upper bound)). On the other hand, the average AUC calculated from under 4 years group was 0.819 for the new processing and 0.678 for the conventional processing (p value= 0.041, 95% confidence interval=0.019/0.262 (lower bound/upper bound)). New image processing provides high detectability in less than 4 years group compared to conventional processing.

Podocyte foot process width is a prediction marker for complete renal response at 6 and 12 months after induction therapy in lupus nephritis.

Morphological change that includes diffuse effacement of podocyte foot processes is correlated with proteinuria in patients with lupus nephritis (LN). We collected the data of clinico-pathological parameters and assessed foot process width (FPW) as an index of podocyte effacement in 73 patients with LN who had undergone renal biopsy. The multivariate analysis revealed that female gender (OR: 5.288; 95%CI: 1.197-37.29; p = .0267) and FPW (OR = 0.999, 95%CI = 0.997-0.999, p = .0150) were significantly predictive of a complete renal response (CR) at 6 months, while lymphocyte counts (OR = 1.002; 95%CI = 1.001-1.003, p = .0028) and FPW (OR = 0.998, 95%CI = 0.996-0.999, p = .0027) were significantly predictive of CR at 12 months. The cut-off point determined by the Classification and Regression Trees algorithm showed that FPW <908.3 nm provides the best performance for predicting patients who achieve CR at 12 months. A smaller FPW appears to be a predictive factor for CR at 6 and 12 months after induction therapy.

A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease.

OBJECTIVE: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established. PATIENTS AND METHODS: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6 mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events. RESULTS: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed. CONCLUSIONS: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.

The Measurement of X-ray Fluoroscopy Input-output Characteristics in Angiography System.

PURPOSE: Determination of X-ray fluoroscopy radiation dose and contrast with angiographic system automatically depending on the objects, and to control setting manually, which is difficult for the measurement of characteristics. Therefore, we examined the method to adjust the conditions of fluoroscopy and measured the input-output characteristics. METHOD: To adjust and fix the condition of fluoroscopy, the exposure adjustment area at the center of the irradiation field was moved to the left side and attached the copper plates to regulate the exposure dose. The area to measure the digital value was selected at the center of the irradiation field, and the dosimeter was placed at the right side of the area, which was selected to measure the digital value. To regulate the entrance dose progressively, the acryl plates were inserted into the irradiation field except for the exposure adjustment area. We obtained a characteristic curve from the measured dose and the digital value. Difference of lookup table (LUT), dose dependency, and tube voltage dependency were checked by the digital characteristic curves. RESULT: Each LUT showed different curves, but they all saturated with 4095, which is the maximum value of 12 bits. Dose dependency was measured as an increase in the permitted dose level with an increase in the setting dose. Tube voltage dependency improved with the tube voltage rises. Each characteristic curve became same by converting the relative exposure dose. As a result, measuring the shape of LUT would be possible. CONCLUSION: The method is useful for measuring the characteristic curve with the X-ray fluoroscopy of angiographic system.

Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus.

INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. METHODS: We analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. RESULTS: Of the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143-2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227-452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six "minimum predictive markers:" IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). CONCLUSIONS: We have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.

Pluripotent stem cells derived from mouse primordial germ cells by small molecule compounds.

Primordial germ cells (PGCs) can give rise to pluripotent stem cells known as embryonic germ cells (EGCs) when cultured with basic fibroblast growth factor (bFGF), stem cell factor (SCF), and leukemia inhibitory factor. Somatic cells can give rise to induced pluripotent stem cells (iPSCs) by introduction of the reprogramming transcription factors Oct4, Sox2, and Klf4. The effects of Sox2 and Klf4 on somatic cell reprogramming can be reproduced using the small molecule compounds, transforming growth factor-ß receptor (TGFßR) inhibitor and Kempaullone, respectively. Here we examined the effects of TGFßR inhibitor and Kempaullone on EGC derivation from PGCs. Treatment of PGCs with TGFßR inhibitor and/or Kempaullone generated pluripotent stem cells under standard embryonic stem cell (ESC) culture conditions without bFGF and SCF, which we termed induced EGCs (iEGCs). The derivation efficiency of iEGCs was dependent on the differentiation stage and sex. DNA methylation levels of imprinted genes in iEGCs were reduced, with the exception of the H19 gene. The promoters of genes involved in germline development were generally hypomethylated in PGCs, but three germline genes showed comparable DNA methylation levels among iEGs, ESCs, and iPSCs. These results show that PGCs can be reprogrammed into pluripotent state using small molecule compounds, and that DNA methylation of these germline genes is not maintained in iEGCs.

Rapid improvement of Clinical Disease Activity Index (CDAI) at 3 months predicts a preferable CDAI outcome at 1 year in active rheumatoid arthritis patients treated with tocilizumab: results from an observational investigation of daily clinical practice.

OBJECTIVES: To investigate whether the Clinical Disease Activity Index (CDAI) at three months predicts a preferable CDAI outcome at one year in patients with active rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: Seventy-eight RA patients in the Nagasaki Prefecture, Japan, whose disease activities at baseline were moderate to high as estimated by the CDAI and who had received 8 mg/kg of TCZ every four weeks, were consecutively enrolled in this study from April 2008 to March 2011. The association of the CDAI at three months with that at one year was examined by the Cochran-Armitage test. The variables at baseline and at three months that were predictive of remission or low disease activity (LDA) according to the CDAI at one year were assessed by logistic regression analysis. RESULTS: Most of the patients (40 out of 44: 91%), whose CDAI at three months showed remission or LDA continued to show remission or LDA at one year. Disease activity at three months significantly correlated with the frequency of LDA or remission at one year (p<0.0001). Logistic regression analysis revealed that only remission or LDA at three months as determined by the CDAI was predictive of remission or LDA at one year as determined by the CDAI (odds ratio 33.2, p<0.0001). CONCLUSIONS: A preferable clinical outcome as estimated by the CDAI at one year in active RA patients treated with TCZ is predicted by the CDAI at three months, suggesting that the treat-to-target strategy carried out using the CDAI can be used in clinical practice in these patients.

Evaluation of switching from intravenous to subcutaneous formulation of tocilizumab in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response. METHODS: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC. RESULTS: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60 kg) as compared with the groups with body weight <60 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC. CONCLUSIONS: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV.

[The Time Sequence Noise Characteristics of the X- ray Fluoroscopic Image].

The role of the X-ray fluoroscopic image during interventional radiology (IVR) is not only the real-time dynamic image for the catheter operation but also to confirm the vascular anatomy using stored image, so that the importance increases more. For the purpose of measuring the time sequence characteristics of X-ray fluoroscopic image, we sampled the digital value of the same coordinate from each X-ray fluoroscopic image and calculated the frequency properties of the noise for the time sequence order as NPStime by performing Fourier transform on the digital value. The parameters, except k-factor which is the time sequence filter, did not influence NPStime. NPStime, which was examined in this study, showed that it is valuable for the method to analyze the time sequence noise characteristics. And, it also showed that it is possible to evaluate the time sequence image processing parameters of X-ray fluoroscopic image by NPStime. Nowadays, each manufacture of the X-ray angiographic system performs the original image processing to their own X-ray fluoroscopic images. The results of the discussion in this study could show the quantitative analysis on the frequency modulation. And it is possible to calculate NPStime by measuring the digital value of stored X-ray fluoroscopic image. The analysis by this method is also technically convenient for the time sequence noise characteristics of the X-ray fluoroscopic image.

Dysregulated mature IL-1ß production in familial Mediterranean fever.

OBJECTIVE: The aim of this study was to analyse the role of circulating cleaved IL-1ß in patients with FMF. METHODS: We enrolled 20 patients with FMF (5 males and 15 females), 22 patients with RA (4 males and 18 females) and 22 healthy controls (6 males and 16 females). Serum levels of serum amyloid A (SAA) were measured by ELISA. We also determined whether IL-1ß was present as the cleaved form (p17) in the sera of FMF patients by immunoblotting using anti-cleaved IL-1ß antibody. RESULTS: Although SAA concentrations were elevated in the sera, there was no significant difference in these concentrations between FMF patients and RA patients. Immunoblot analysis demonstrated that the cleaved form of IL-1ß (p17) was present in sera from FMF patients during febrile attack periods, but not in healthy controls. Bands representing the cleaved form of IL-1ß were not detected in serum from FMF patients at non-febrile attack periods or remission periods under colchicine treatment. The amounts of cleaved IL-1ß (p17) were significantly higher in patients with FMF compared with those in patients with RA in the inflammatory phase. CONCLUSION: The cleaved form of IL-1ß is a valuable biomarker for monitoring disease activity and response to colchicine treatment in patients with FMF. It might be useful to discriminate FMF from other non-IL-1ß-mediated inflammatory disorders.

Induction of primordial germ cell-like cells from mouse embryonic stem cells by ERK signal inhibition.

Primordial germ cells (PGCs) are embryonic germ cell precursors. Specification of PGCs occurs under the influence of mesodermal induction signaling during in vivo gastrulation. Although bone morphogenetic proteins and Wnt signaling play pivotal roles in both mesodermal and PGC specification, the signal regulating PGC specification remains unknown. Coculture of mouse embryonic stem cells (ESCs) with OP9 feeder cells induces mesodermal differentiation in vitro. Using this mesodermal differentiation system, we demonstrated that PGC-like cells were efficiently induced from mouse ESCs by extracellular signal-regulated kinase (ERK) signaling inhibition. Inhibition of ERK signaling by a MAPK/ERK kinase (MEK) inhibitor upregulated germ cell marker genes but downregulated mesodermal genes. In addition, the PGC-like cells showed downregulation of DNA methylation and formed pluripotent stem cell colonies upon treatment with retinoic acid. These results show that inhibition of ERK signaling suppresses mesodermal differentiation but activates germline differentiation program in this mesodermal differentiation system. Our findings provide a new insight into the signaling networks regulating PGC specification.

Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis.

OBJECTIVE: We have tried to clarify the clinical importance of the measurement of serum type-I interferon (IFN) in patients with anti-melanoma differentiation-associated gene 5 Ab (MDA5 Ab)-positive dermatomyositis (DM). METHODS: We studied 30 patients with DM: 10 were anti-MDA5 Ab-positive and 20 were anti-MDA5 Ab-negative. At each patient's initial visit, serum IFN-α, IFN-ß, interleukin 18 (IL-18), ferritin, and the titer of anti-MDA5 Ab were measured using enzyme-linked immunosorbent assays (ELISAs). The associations between the IFNs and with the other variables were examined. RESULTS: Rapidly progressive interstitial lung disease (RPILD) was confirmed in 10 patients, most of whom were complicated in the anti-MDA5 Ab-positive DM patients. The presence of clinically amyopathic dermatomyositis (CADM) as well as the serum concentrations of IFN-α and ferritin was significantly higher in the anti-MDA5 Ab-positive DM patients. Serum concentration of IL-18 did not differ between anti-MDA5 Ab-positive and anti-MDA5 Ab-negative groups; however, a positive correlation was found between IFN-α and IL-18 in the anti-MDA5 Ab-positive DM patients (r = 0.8139, p = 0.0146). CONCLUSION: Serum IFN-α can be used as a useful biomarker in patients with anti-MDA5 Ab-positive DM, which may reflect the presence of RPILD.

The impact of glucocorticoid use on the outcomes of rheumatoid arthritis in a multicenter ultrasound cohort study.

OBJECTIVE: Glucocorticoids are effective in treating rheumatoid arthritis (RA) when used appropriately considering the balance of the risks and benefits, especially at low doses. We aimed to evaluate the response of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients having already been treated with glucocorticoids. METHODS: We reviewed RA patients treated with b/tsDMARDs in a prospective multicenter ultrasound cohort study. We compared the differences in the clinical characteristics at baseline and outcomes at 12 months between the two groups having been treated with and without glucocorticoids at baseline. The differences in the clinical characteristics and the treatments were balanced by the inverse probability weighting (IPW) with the propensity score. RESULTS: Of 307 patients with RA, 160 patients were treated with glucocorticoids at baseline. The median dose of glucocorticoids was equivalent to 5.0 mg/day of prednisolone. Significant differences were in age and concomitant methotrexate use, composite measures for the disease activity, and the ultrasound grayscale score at baseline. Patients treated with glucocorticoids had less frequent remissions defined by composite measures and ultrasound findings than those treated without glucocorticoids. These significant differences in the achievement of remissions remained robust even after adjusting differences in the clinical characteristics and the treatments between the two groups by IPW. CONCLUSION: RA patients treated with glucocorticoids had a higher disease activity at baseline and a poorer response to treatments with b/tsDMARDs than those without glucocorticoids. The states of patients requiring glucocorticoids might be associated with the poor response to the b/tsDMARDs.

Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins.

OBJECTIVE: To identify the 140-kd autoantigen recognized by anti-155/140 autoantibodies that are associated with adult cancer-associated dermatomyositis (DM) and juvenile DM and to determine the clinical relevance of anti-155/140 antibodies in a large cohort. METHODS: Sera from 456 DM patients were assessed for the presence of anti-155/140 antibodies by immunoprecipitation using K562 cell extracts as substrate. Using immunoprecipitation and Western blotting, we then examined whether anti-155/140-positive sera recognized transcription intermediary factor 1α (TIF-1α), TIF-1ß, and TIF-1γ. The clinical associations of antigen reactivity were also evaluated. RESULTS: Anti-155/140-positive sera reacted with 140-kd TIF-1α in addition to 155-kd TIF-1γ. Among sera from 456 DM patients, 52 were reactive with both TIF-1α and TIF-1γ, while another 25 were reactive with TIF-1γ alone. Additionally, 7 were reactive with TIF-1ß. Malignancy was more frequently found in adult patients with both anti-TIF-1α and anti-TIF-1γ antibodies than in those with anti-TIF-1γ antibodies alone (73% versus 50%; P < 0.05). In addition to juvenile DM patients and middle-aged and older DM patients with high percentages of malignancy, 8 "young adult" DM patients without malignancy had these autoantibodies. CONCLUSION: Anti-155/140 antibodies target TIF-1 family proteins, TIF-1α and TIF-1ß, in addition to TIF-1γ. Since TIF-1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.