Clinical characteristics and treatment of elderly onset adult-onset Still's disease.

Adult-onset Still's disease (AOSD)-a systemic inflammatory disease-often occurs at a young age. Recently, elderly onset patient proportion has been increasing; however, data are limited. To evaluate the characteristics of elderly patients with AOSD in a multicenter cohort, we retrospectively analyzed 62 patients with AOSD at five hospitals during April 2008-December 2020.

Enhanced expression of mRNA for transforming growth factor β activated kinase 1 in CD34+ cells of the bone marrow in rheumatoid arthritis.

Objectives: Transforming growth factor β activated kinase 1 (TAK1) has been found to mediate maladaptive tumour necrosis factor (TNF) signalling, leading to hyperactive downstream nuclear factor Kappa β (NF-κB) signalling. We explored the expression of TAK1 mRNA in bone marrow CD34+ cells in rheumatoid arthritis (RA) to delineate the mechanism for their abnormal response to TNF-α and differentiate into fibroblast-like cells.

Methods: CD34+ cells were purified from bone marrow samples obtained from 47 RA patients and 27 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest.

Association of NCF1 polymorphism with systemic lupus erythematosus and systemic sclerosis but not with ANCA-associated vasculitis in a Japanese population.

Genome-wide association studies of systemic lupus erythematosus (SLE) in Chinese and Korean populations demonstrated strong association of single nucleotide polymorphisms (SNPs) located in the GTF2I-NCF1 region, rs73366469 (GTF2I), rs117026326 (GTF2I), rs80346167(GTF2IRD1) and rs201802880 (NCF1). This region has also been associated with susceptibility to Sjögren syndrome and rheumatoid arthritis; however, association studies with systemic sclerosis (SSc) and ANCA-associated vasculitis (AAV) have not been reported. Here we made an attempt to confirm their associations with SLE in the Japanese population, to find the primarily associated SNP, and to investigate whether these SNPs are also associated with susceptibility to SSc and AAV.

Synergistic enhancement of production of proinflammatory cytokines of human peripheral blood monocytes by anti-Sm and anti-RNP antibodies.

The present study was performed to elucidate the roles of serum anti-Sm antibodies in the pathogenesis of systemic lupus erythematosus (SLE). Highly purified peripheral blood monocytes obtained from healthy donors were cultured in the presence of monoclonal anti-Sm antibody (anti-Sm mAb), monoclonal anti-U1-RNP antibody (anti-RNP mAb) or control murine IgG1 or IgG3. After various periods of incubation, levels of IL-6 and TNF-α in the culture supernatants were measured by ELISA and the expression of mRNA for various molecules in monocytes was determined using RT-PCR.

Elevation of serum anti-glucose-regulated protein 78 antibodies in neuropsychiatric systemic lupus erythematosus.

Objective: Recent studies have demonstrated that autoantibodies directed against glucose-regulated protein 78 (GRP78) on endothelial cells promote blood-brain barrier (BBB) damages. The present study examined whether serum anti-GRP78 antibodies might be involved in the pathogenesis of neuropsychiatric SLE (NPSLE).

Methods: Serum samples were obtained from 129 patients with SLE (58 patients with diffuse psychiatric/neuropsychological syndromes of NPSLE (diffuse NPSLE), 30 with neurological syndromes (focal NPSLE), 21 with lupus nephritis (LN), 20 without NPSLE or LN (SLE alone)), from 35 patients with non-SLE rheumatic diseases (non-SLE RD) and from 24 healthy controls (HC).

Effects of CTLA4-Ig on human monocytes.

Background: Abatacept, a CTLA4-Ig fusion protein attenuates T cell activation by inhibiting the CD80/86-CD28 costimulatory pathway that is required for the proper T cell activation and thus displays beneficial effects in the treatment of rheumatoid arthritis (RA). Although some studies have disclosed the in vitro effects of this biological agent on the immune-competent cells, the precise mechanisms of action in RA still remain unclear. The current studies were therefore undertaken to explore the effects of abatacept on monocytes in detail.

The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD34+ cells in rheumatoid arthritis.

Objectives: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients.

Differential influences of Fc gamma receptor blocking on the effects of certolizumab pegol and infliximab on human monocytes.

Objectives: To compare the effects of certolizumab pegol (CZP) and infliximab (IFX) on human monocytes.

Methods: Highly purified monocytes from healthy donors were cultured with CZP, IFX, control IgG1, or polyethylene glycol (PEG) at pharmacological attainable concentrations in culture medium with 10% autologous normal human serum (NHS) or with fetal bovine serum (FBS) for 24 h, after which the supernatants were replaced by fresh culture medium containing LPS. After additional 24 h of incubation, the supernatants were assayed for TNF-α and IL-6.

Association of HLA-G 3' Untranslated Region Polymorphisms with Systemic Lupus Erythematosus in a Japanese Population: A Case-Control Association Study.

HLA-G plays a role in fetal-maternal tolerance as well as immunoregulation, and has been suggested to be involved in autoimmune diseases and cancers. HLA-G encodes two potentially functional polymorphisms in the 3' untranslated region, 14bp insertion/deletion (14bp indel, rs371194629) and a single nucleotide polymorphism rs1063320, previously reported to affect HLA-G expression level or splicing isoform and to be associated with susceptibility to systemic lupus erythematosus (SLE). However, the results of SLE association studies are inconsistent, probably due to the small sample size of each study and lack of consideration of linkage disequilibrium (LD) with HLA-class II haplotypes in each population.

Differential activation mechanisms of serum C5a in lupus nephritis and neuropsychiatric systemic lupus erythematosus.

Objective: To explore the role of C5a in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and lupus nephritis (LN).

Methods: Sera were obtained from 29 patients with NPSLE, 25 with LN, 26 without NPSLE or LN [SLE alone], and 21 healthy donors. Cerebrospinal fluid (CSF) was obtained from 29 NPSLE patients.

Human Leukocyte Antigen and Systemic Sclerosis in Japanese: The Sign of the Four Independent Protective Alleles, DRB1*13:02, DRB1*14:06, DQB1*03:01, and DPB1*02:01.

Objective: Several studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic sclerosis (SSc) have been reported. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are found in SSc patients. Here, we sought to identify HLA alleles associated with SSc in Japanese, and explored their associations with SSc phenotypes including the presence of autoantibodies.

Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors with neuropsychiatric systemic lupus erythematosus.

Objective: To determine epitope reactivity of autoantibodies to N-methyl-D-aspartate (NMDA) receptor NR1 subunit and their association with neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods: Paired serum and CSF specimens were obtained from 41 patients with NPSLE (22 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 19 with neurologic syndromes or polyneuropathy [focal NPSLE]), 21 patients with various rheumatic diseases other than SLE (non-SLERD). Sera were also obtained from 27 SLE patients without neuropsychiatric manifestations (non-CNS SLE).

Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus.

Background: Manifestations in neuropsychiatric systemic lupus erythematosus (NPSLE), especially active diffuse NPSLE syndromes, are some of the most difficult complications of the disease. For the evaluation and the diagnosis of central nervous system manifestations, including NPSLE, MRI is a very useful tool to detect the various abnormalities. However, the relationship between brain MRI findings and clinical variables has not yet been clarified in patients with diffuse NPSLE.

Association of functional polymorphisms in interferon regulatory factor 2 (IRF2) with susceptibility to systemic lupus erythematosus: a case-control association study.

Interferon regulatory factor 2 (IRF2) negatively regulates type I interferon (IFN) responses, while it plays a role in induction of Th1 differentiation. Previous linkage and association studies in European-American populations suggested genetic role of IRF2 in systemic lupus erythematosus (SLE); however, this observation has not yet been confirmed. No studies have been reported in the Asian populations.

Transverse myelitis extended to disseminated encephalitis in systemic lupus erythematosus: Histological evidence for vasculitis.

A 42-year-old woman was admitted due to systemic lupus erythematosus complicated with glomerulonephritis and pulmonary hypertension. During the treatment for these complications, she presented motor paresis and sensory loss caused by transverse myelitis. In spite of methyl prednisolone pulse therapy, she further developed acute confusional state due to disseminated encephalitis and fell into respiratory arrest.

Effects of anti-IL-6 receptor antibody on human monocytes.

Objective: To explore the effects of anti-IL-6 receptor antibody, tocilizumab on function of human monocytes.

Methods: Monocytes from healthy donors were cultured in the presence of staphylococcal enterotoxin B (SEB) with pharmacologically attainable concentrations of tocilizumab or control IgG. The expression of IL-6 mRNA was determined using quantitative RT-PCR.

Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03.

Many studies on associations between human leukocyte antigen (HLA) allele frequencies and susceptibility to systemic lupus erythematosus (SLE) have been performed. However, few protective associations with HLA-DRB1 alleles have been reported. Here, we sought protective, as well as predispositional, alleles of HLA-DRB1 in Japanese SLE patients.

[An adult case of acute pericarditis and glomerulonephritis associated with human parvovirus B19 infection].

We report herein on a 52-year-old Japanese woman with acute pericarditis and glomerulonephritis associated with human parvovirus B19 infection, who had no significant medical history. The patient was admitted for progressive edema and upper abdominal pain. On physical examination, she had hypertension, generalized edema and upper abdominal tenderness.

Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients.

Introduction: Autoantibodies to ribonucleoprotein are associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA). Many studies on associations between human leukocyte antigen (HLA) alleles and RA have been reported, but few have been validated in RA subpopulations with anti-La/SS-B or anti-Ro/SS-A antibodies. Here, we investigated associations of HLA class II alleles with the presence of anti-Ro/SS-A or anti-La/SS-B antibodies in RA.

Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation.

Objectives: We previously disclosed the enhanced expression of FK506 binding protein 5 (FKBP5) messenger RNA (mRNA) in bone marrow (BM) CD34(+) cells in rheumatoid arthritis (RA), in which systemic osteoporosis takes place. Since BM CD34(+) cells are precursors of osteoclasts, it is possible that FKBP5 overexpression might lead to osteoporosis by affecting osteoclastogenesis. We therefore explore the influences of FKBP5 in osteoclast differentiation.

Incidence and the risk factor of malignancy in Japanese patients with systemic sclerosis.

Objective: To evaluate the incidence and risk factors for malignancy in Japanese patients with systemic sclerosis (SSc).

Methods: A cohort of 405 Japanese patients with SSc who visited Kitasato University hospital between 1973 and 2008 was analyzed retrospectively until the end of 2009. The incidence of malignancy was compared with that of the general population, with calculation of the standardized incidence ratio (SIR) and 95% confidence interval (CI).

Induction of type B synoviocyte-like cells from plasmacytoid dendritic cells of the bone marrow in rheumatoid arthritis and osteoarthritis.

We examined the capacities of bone marrow (BM) plasmacytoid dendritic cells (pDC) to differentiate into type B synoviocyte-like cells. BM aspiration samples were obtained from 24 rheumatoid arthritis (RA) patients and 19 osteoarthritis (OA) patients during joint operations from the iliac crest. CD34+ cells and pDC purified from BM mononuclear cells were cultured with or without SCF, GM-CSF, and TNF-α for 2-4 weeks.

Anti-ribosomal P protein antibody induces Th1 responses by enhancing the production of IL-12 in activated monocytes.

Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of patients with systemic lupus erythematosus (SLE), and have been found to be associated with some manifestations, including lupus psychosis, nephritis and hepatitis. We have recently disclosed that anti-P react with activated human peripheral blood monocytes, and enhance their production of tumor necrosis factor-α and interleukin (IL)-6. It is also possible that anti-P might regulate other monocyte functions, including the regulation of T helper (Th) responses.

Impact of angiotensin-converting enzyme inhibition on renal cortical nitrotyrosine content during increased extracellular glucose concentration.

Objectives: Experiments evaluated the hypothesis that angiotensin-converting enzyme (ACE) inhibition suppresses hyperglycemia-induced nitrotyrosine (NT) production in the renal cortex.

Design And Methods: Rats were untreated (UNTR, n = 6) or received the ACE inhibitor enalapril (20 mg/kg/day; ENAL, n = 6) for 2 weeks. Renal cortical slices were incubated for 90 min in media containing 5 (normal) or 20 mmol/L (high) glucose.

Apoptosis and adhesion of hemocytes during molting stage of silkworm, Bombyx mori.

To clarify the regulatory mechanism of the rapid changes in the hemocyte density in the silkworm, Bombyx mori, during ecdysis, we evaluated the relationship between the hemocyte density and the incidence of apoptosis during this stage. We also evaluated the role of the sugar chains on the adhesion of hemocytes by analyzing the effects on the hemocyte density of the injection of enzymes that cut sugar chains and monosaccharides into the body cavity. The hemocyte density was increased in the molting stage and spinning, and then decreased after the ecdysis.