The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial.

Background: Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients.

Reduced induction of anti-PF4/heparin antibody in RA patients after total knee arthroplasty.

Background: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty.

Methods: The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis.

Familial Mediterranean fever is no longer a rare disease in Japan.

Background: The aim of this study was to evaluate the clinical manifestations and prevalence of familial Mediterranean fever (FMF) in Japanese patients with unexplained fever and rheumatic manifestations.

Methods: We enrolled 601 patients with unexplained fever or suspected FMF throughout Japan between 2009 and 2015. Patients were divided into three groups according to Tel Hashomer criteria: sure FMF, probable FMF, and non-FMF patients, including definitive rheumatic diseases.

Effects of a Foot Pump on the Incidence of Deep Vein Thrombosis After Total Knee Arthroplasty in Patients Given Edoxaban: A Randomized Controlled Study.

We conducted a randomized clinical trial to compare the effectiveness of the A-V Impulse System foot pump for reducing the incidence of deep-vein thrombosis (DVT) after total knee arthroplasty (TKA) in patients under edoxaban thromboprophylaxis. Patients undergoing primary TKA at our institution between September 2013 and March 2015 were enrolled after obtaining informed consent. The patients were randomized to use the foot pump (n = 58) and not to use the foot pump (n = 62).

Opsonic and Antibody Responses to Pneumococcal Polysaccharide in Rheumatoid Arthritis Patients Receiving Golimumab Plus Methotrexate.

Vaccination against Streptococcus pneumoniae is recommended for rheumatoid arthritis (RA) patients receiving immunosuppressive treatments. The objective of this study was to evaluate the humoral response to 23-valent pneumococcal polysaccharide vaccination (PPSV23) in RA patients receiving methotrexate (MTX) alone or in combination with a tumor necrosis factor inhibitor, golimumab (GOM).PPSV23 was given to 114 RA patients, who were classified into three groups: RA control (n = 35), MTX alone (n = 55), and GOM + MTX (n = 24).

Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population.

Background: Previous genome-wide association studies have evaluated the impact of common genetic variants and identified several non-HLA risk loci associated with autoimmune liver diseases. More recent genome-wide association studies and replication analyses reported an association between variants of the CARD10 polymorphism rs6000782 and risk of type 1 autoimmune hepatitis (AIH). In this case-control study, we genotyped 326 Japanese AIH patients and 214 control subjects.

Circulating microRNA Profiles in Patients with Type-1 Autoimmune Hepatitis.

Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database.

Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy.

Few data are available regarding vertebral fracture risk in patients treated with corticosteroids including patients with interstitial lung disease (ILD). The aim of the present study was to identify risk factors for symptomatic vertebral fracture analyzed in patients with newly diagnosed autoimmune diseases.This was an observational cohort study conducted in the National Hospital Organization-EBM study group from 2006 to 2008.

Risk of venous thromboembolism after total knee arthroplasty in patients with rheumatoid arthritis.

Objective: To compare the incidence of venous thromboembolism (VTE) following total knee arthroplasty (TKA) between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA).

Methods: The subjects were composed of 1084 Japanese patients with OA and 204 with RA. Primary effectiveness outcomes were any deep vein thrombosis (DVT) as detected by bilateral ultrasonography up to postoperative Day 10 (POD10) and pulmonary embolism (PE) up to POD28.

Predictors of mortality in patients with interstitial lung disease treated with corticosteroids: results from a cohort study.

Interstitial lung disease (ILD) has a heterogeneous clinical presentation and establishing prognosis for these patients is challenging. We investigated the clinical characteristics and outcome of patients with idiopathic interstitial pneumonias (IIPs) and patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). We conducted a multicenter prospective study on 104 patients diagnosed with IIPs and 29 patients diagnosed with CTD-ILD, which were newly diagnosed and treated with corticosteroids initially.

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

Objective: The aim of this study was to analyse the role of circulating cleaved IL-1β 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.

Serum amyloid A induces NLRP-3-mediated IL-1β secretion in neutrophils.

Background/aims: Serum amyloid A (SAA) is an acute phase reactant with significant immunological activities, including effects on cytokine synthesis and neutrophil chemotaxis. Neutrophils can also release cytokines with proinflammatory properties. IL-1β is a key proinflammatory cytokine, the secretion of which is controlled by inflammasome.

Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV) mutations. In Japan, patients with FMF have been previously reported, including a mild or incomplete form. Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF.

[An usual case of vasculo- and neuro-Behçet's disease with MEFV mutations].

  A 35-year-old man had a 2-year history of uveitis and arterial wall thickening of an aortic branching artery detected by magnetic resonance imaging. He was admitted to our hospital because of mental exaltation. He had been treated with a moderate dose of prednisolone (30 mg/ml) plus methotrexate (6 mg/week) under the diagnosis of Takayasu arteritis for 2 years.

Coexistence of familial Mediterranean fever and rheumatoid arthritis.

Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent febrile polyserositis and arthritis. Although accompanying seronegative spondyloarthropathy has been reported in FMF, coexistence with rheumatoid arthritis (RA) is very rare. This case report describes a Japanese female RA patient who presented with periodic fever.

IgG4-related epididymo-orchitis associated with bladder cancer: possible involvement of BAFF/BAFF-R interaction in IgG4-related urogenital disease.

We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues.

Rates of serious intracellular infections in autoimmune disease patients receiving initial glucocorticoid therapy.

Background/aims: The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs.

Methodology/principal Findings: A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009.

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

Background/aims: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.

Methodology/principal Findings: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694).

The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.

Background/aims: Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors.

Methodology/principal Findings: In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1β) gene polymorphisms may affect the susceptibility of Japanese patients with FMF.

Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts.

Background: Monosodium urate (MSU) has been shown to promote inflammasome activation and interleukin-1β (IL-1β) secretion in monocyte/macrophages, but the cellular pathway and nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in synovial tissues, remain elusive. In this study, we investigated the effects of MSU on synovial fibroblasts to elucidate the process of MSU-mediated synovial inflammation.

Methods: Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA).

Coexistence of polymyositis and familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting populations surrounding the Mediterranean area. In this case report, we report a Japanese female patient with polymyositis (PM) who presented with periodic fever. Genetic analysis revealed that she had compound heterozygous mutations in exon 2 of the MEFV gene (L110P/E148Q/R202Q).

Serum amyloid A (SAA) induces pentraxin 3 (PTX3) production in rheumatoid synoviocytes.

Objective: Pentraxin 3 (PTX3) is an acute-phase reactant that is involved in amplification of the inflammatory response and innate immunity. In the present study, we evaluated the relationship between PTX3 and serum amyloid A (SAA), another acute-phase reactant, in rheumatoid synoviocytes.

Methods: PTX3 mRNA expression was examined by reverse transcription polymerase chain reaction, and PTX3 protein was measured by enzyme-linked immunosorbent assay.

Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization-autoimmune hepatitis prospective study).

Background/aims: Although the outcome of autoimmune hepatitis (AIH) is generally good, the natural course and likelihood of progression to cirrhosis or hepatocellular carcinoma (HCC) remain undefined, and may vary by region and population structure. Our aims were to evaluate risk factors that contribute to poor outcome and particularly development of HCC in a prospective multicentric cohort study of AIH.

Methods: The study group comprised 193 Japanese patients with AIH who were prospectively followed up at annual intervals between 1995 and 2008.