Genetic architecture underlying IgG-RF production is distinct from that of IgM-RF.

Objective: HLA-DRB1 alleles, particularly the shared epitope (SE) alleles, are strongly associated with RA. Different genetic structures underlie the production of the various autoantibodies in RA. While extensive genetic analyses have been conducted to generate a detailed profile of ACPA, a representative autoantibody in RA, the genetic architecture underlying subfractions of RF other than IgM-RF, namely IgG-RF, known to be associated with rheumatoid vasculitis, is not well understood.

A Novel CD135 Subset of Mouse Monocytes with a Distinct Differentiation Pathway and Antigen-Presenting Properties.

The mononuclear phagocyte system (MPS), composed of monocytes/macrophages and dendritic cells (DCs), plays a critical role at the interface of the innate and adaptive immune systems. However, the simplicity of MPS has been challenged recently by discoveries of novel cellular components. In the current study, we identified the CD135 subset of monocytes as a novel class of APCs in mice.

Co-occurrence of relapsing polychondritis and autoimmune thyroid diseases.

Background: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves' disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD.

Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs.

Two gray γ-irradiation is a widely employed basic module for total body irradiation (TBI) in allogeneic hematopoietic cell transplantation (HCT). The effects of γ-irradiation on hematopoietic and immune cells have been well investigated, but its effects on the bone marrow microenvironment (BMM) are unknown. Given the crucial contribution of mesenchymal/stromal stem cells (MSCs) in the BMM to hematopoiesis and osteogenesis, we investigated whether γ-irradiation affects the hallmark characteristics of human bone marrow-derived MSCs (BM-MSCs).

Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency.

Background: The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD.

Correction to: Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells.

In the original publication of the article, the Figs. 4 C, F and 5 B, C were published with unexpected appearance of dots.

C/EBPβ isoforms sequentially regulate regenerating mouse hematopoietic stem/progenitor cells.

The transcription factor CCAAT enhancer-binding protein β (C/EBPβ) is required for stress-induced granulopoiesis at the level of hematopoietic stem/progenitor cells (HSPCs); however, its role and mechanisms of action in HSPCs are unknown. In this study, we assessed the regulation and functions of C/EBPβ in HSPCs, especially under stress conditions. After 5-fluorouracil treatment or bone marrow transplantation, Cebpb-/- HSPCs exhibited impaired cell-cycle activation and myeloid differentiation at the early and late phases of regeneration, respectively, whereas at steady state, Cebpb deficiency did not affect HSPCs.

Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells.

Vitamin K2 in the form of menatetrenone has clinical benefits for osteoporosis and cytopenia. Given the dominant role of mesenchymal-osteolineage cells in the regulation of hematopoiesis, we investigated whether menatetrenone alters the hematopoiesis-supportive capability of human bone marrow mesenchymal stromal/stem cells (BM-MSCs). Menatetrenone up-regulated fibronectin protein expression in BM-MSCs without affecting their proliferation and differentiation capabilities.

Successful granulocyte apheresis using medium molecular weight hydroxyethyl starch.

Granulocyte transfusion (GTX) is a therapeutic option for severe bacterial or fungal infection in patients with sustained neutropenia after chemotherapy or stem cell transplantation. However, high molecular weight hydroxyethyl starch (HES), which has been used for selective sedimentation of red blood cells during apheresis, is not easily available in many countries including Japan. In this study, we evaluated the efficiency of granulocyte collection using medium molecular weight HES (130 kDa) in combination with the Spectra Optia apheresis system.

C/EBPβ is a critical mediator of IFN-α-induced exhaustion of chronic myeloid leukemia stem cells.

Even in the era of ABL tyrosine kinase inhibitors, eradication of chronic myeloid leukemia (CML) stem cells is necessary for complete cure of the disease. Interferon-α (IFN-α) has long been used for the treatment of chronic-phase CML, but its mechanisms of action against CML stem cells remain unclear. We found that IFN-α upregulated CCAAT/enhancer binding protein β (C/EBPβ) in BCR-ABL-expressing mouse cells by activating STAT1 and STAT5, which were recruited to a newly identified 3' distal enhancer of that contains tandemly aligned IFN-γ-activated site elements.

Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

Objective: is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF.

Methods: A total of 2873 patients with RA and 2008 healthy controls were recruited.

Multiple myeloma cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation.

The emergence of new molecular targeting agents has improved the prognosis of patients with multiple myeloma (MM). However, MM remains incurable because MM stem cells are likely resistant to these agents. Thus, it is important to further investigate the biology of MM stem cells, which reside in the hypoxic bone marrow niche.

Effects of acute exposure to low-dose radiation on the characteristics of human bone marrow mesenchymal stromal/stem cells.

Background: In recent years, increasing attention has been paid to the effects of low-dose irradiation on human health. We examined whether low-dose irradiation affected the functions of mesenchymal stromal/stem cells (MSCs), which are tissue/organ-supportive stem cells, derived from bone marrow (BM).

Methods: Normal human BM-MSCs from five healthy individuals were used in this study.

Pharmacological targeting of bone marrow mesenchymal stromal/stem cells for the treatment of hematological disorders.

The therapeutic effects of mesenchymal stromal/stem cells (MSCs) are mainly based on three characteristics: immunomodulation, tissue regeneration, and hematopoietic support. Cell therapy using culture-expanded MSCs is effective in some intractable bone and hemato-immune disorders; however, its efficacy is limited. In this article, we review the previous efforts to improve the clinical outcomes of cell therapy using MSCs for such disorders.

C/EBPβ is required for survival of Ly6C monocytes.

The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis.

A Rare Case of Adult Autoimmune Neutropenia Successfully Treated with Prednisolone.

Autoimmune neutropenia (AIN) is a rare disorder that may cause life-threatening infections. In adults, most cases are secondary to other pathological conditions, and primary AIN is extremely rare. We herein report a case involving a 57-year-old woman diagnosed with AIN.

Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells.

Umbilical cord blood (UCB) has advantages over other tissues because it can be obtained without an invasive procedure and complex processing. We explored the availability of cryopreserved UCB cells as a source of mesenchymal stromal/stem cells (MSCs). MSCs were successfully isolated from six of 30 UCB units (median volume, 34.

Impact of Antibodies That React With Liver Tissue and Donor-Specific Anti-HLA Antibodies in Pediatric Idiopathic Posttransplantation Hepatitis.

Background: The cause of late graft dysfunction has not been elucidated. Although an antibody-mediated reaction is suspected as a potential mechanism, the target antigens have not been clarified.

Methods: To clarify the etiology of idiopathic posttransplantation hepatitis (IPTH), we simultaneously examined the presence of antibodies that react with liver tissue (ARLT) by means of indirect immunofluorescence staining, as well as the presence of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA).

[Ethics for clinical research].

In order to translate research results obtained with technical innovations into the novel therapeutic approaches expeditiously, it is mandatory that both researchers and clinicians collaborate with pharmaceutical companies. In other words, investigators, pharmaceutical companies, and patients should work together to make newly innovative drugs more patient-friendly and more effective, with fewer adverse side effects. Patient cooperation is also indispensable for carrying out investigator-initiated clinical trials providing informative evidence for the development of clinical practice guidelines.

Genotyping of relapsing polychondritis identified novel susceptibility HLA alleles and distinct genetic characteristics from other rheumatic diseases.

Objective: To uncover the genetic background of relapsing polychondritis (RPC), a rare autoimmune disease with unknown mechanisms characterized by systemic inflammation of the cartilage, to deepen our understanding of the pathophysiology of RPC and show its distinct genetic characteristics from other rheumatic diseases.

Methods: A total of 102 patients with RPC and 1000 healthy subjects were recruited for a two-staged genetic association study and genotyped for six HLA classical loci. Haplotype association tests were also performed.

Combination of panobinostat with ponatinib synergistically overcomes imatinib-resistant CML cells.

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR-ABL gene amplification or mutation. We investigated the cytotoxicity of a pan-ABL tyrosine kinase inhibitor, ponatinib, and a pan-histone deacetylase inhibitor, panobinostat, against IM-resistant CML cells in vitro. Two different IM-resistant cell lines, K562/IM-R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3.