Abstract:
:Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive nontargeted metabolomics approach combining capillary electrophoresis time-of-flight mass-spectrometry (TOFMS) and liquid chromatography TOFMS. We constructed metabolomics profiling of 286 plasma samples of the Japanese population. (92 RA patients, 13 systemic lupus erythematosus (SLE) patients, and 181 healthy controls). RA case-control association tests showed that seven metabolites exhibited significantly increased levels in RA samples than in controls [P & 1.0×10 -4; UTP, ethanolamine phosphate, ATP, GDP, ADP, 6-aminohexanoic acid, and taurine], whereas one exhibited a decreased level (xanthine). The plasma levels of these eight metabolites were not significantly different between seropositive and seronegative RA patients (P > 0.05; n = 68 and 24, respectively). The four nucleotide levels (UTP, ATP, GDP, and ADP) were significantly higher in the non-treatment patients in comparison between patients with and without treatment (P & 0.014; n = 57 and 35, respectively). Furthermore, we found that none of the four nucleotides levels showed significant differences in SLE case-control association tests (P > 0.2; 13 patients with SLE and the 181 shared controls) and psoriatic arthritis (PsA) case-control association tests (P > 0.11; 42 patients with PsA and 38 healthy controls), indicating disease specificity in RA. In conclusion, our large-scale metabolome analysis demonstrated the increased plasma nucleotides levels in RA patients, which could be used as potential clinical biomarkers of RA, especially for seronegative RA.
journal_name
Int Immunoljournal_title
International immunologyauthors
Kishikawa T,Maeda Y,Nii T,Arase N,Hirata J,Suzuki K,Yamamoto K,Masuda T,Ogawa K,Tsuji S,Matsushita M,Matsuoka H,Yoshimura M,Tsunoda S,Ohshima S,Narazaki M,Ogata A,Saeki Y,Inohara H,Kumanogoh A,Takeda K,Okada Ydoi
10.1093/intimm/dxaa059subject
Has Abstractpub_date
2020-08-31 00:00:00eissn
0953-8178issn
1460-2377pii
5899786pub_type
杂志文章abstract::Dendritic cells (DCs) are specialized antigen-presenting cells that play pivotal roles in initiating immune responses. However, DC maturation is usually strongly restricted by the stromal microenvironment, especially in non-lymphoid tissues, such as skin and mucosa. Although suppression of DC maturation by stromal cel...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn078
更新日期:2008-09-01 00:00:00
abstract::Virus-like particles are a highly effective type of subunit vaccine that mimics the overall structure of virus particles without containing infectious genetic material. In this work, a particulate form of the recombinant capsid protein from dengue-2 was evaluated in mice to determine the level of protection against vi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxp082
更新日期:2009-10-01 00:00:00
abstract::The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by anti...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg049
更新日期:2003-04-01 00:00:00
abstract::Deletion of alpha i2 subunit of heterotrimeric G proteins induces a 2-4-fold increase in the proportions of CD4 and CD8 single-positive (SP) thymocytes as compared with wild-type littermates, but how G alpha i2 is involved in thymocyte development is unknown. To determine a role for G alpha i2 in a specific developmen...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxh204
更新日期:2005-03-01 00:00:00
abstract::Naturally occurring CD4(+)CD25(+) regulatory T cells (nT(R)) comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. Here we demonstrate that the level of phosphorylation of the TCR zeta-chain is approximately 1.5- to 4-fold higher in nT(R) as compared with CD4(+)CD25...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxm021
更新日期:2007-04-01 00:00:00
abstract::In the final analysis, the self (S)-non-self (NS) discrimination is regulated by the sufficiency or insufficiency of effector T(h) (eT(h)) specific for the given antigen. We have described a model (Th genesis) for the origin of eT(h) based on an antigen-independent pathway from initial state T(h) (iT(h)) to eT(h), and...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg059
更新日期:2003-05-01 00:00:00
abstract::Organs of transgenic pigs that express human complement regulatory proteins are under assessment as an alternative to transplantation. A major barrier to the transplantation of pig organs is the hyperacute rejection caused by pre-existing antibodies and complement. Pig cells are very susceptible to human complement, p...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/9.6.869
更新日期:1997-06-01 00:00:00
abstract::T-cell immune responses are critical for protection of the host and for disease pathogenesis during infection with Plasmodium species. We examined the regulation of CD4(+) T-cell cytokine responses during infection with Plasmodium berghei ANKA (PbA). CD4(+) T cells from PbA-infected mice produced IFN-γ, IL-4 and IL-10...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq448
更新日期:2010-12-01 00:00:00
abstract::Experiments in transgenic mice have demonstrated that thymocyte differentiation into the mature CD4+ helper or CD8+ cytotoxic T cell lineage is ultimately dependent upon the specificity of the TCR for class II or class I MHC molecules respectively. However, the initial mechanistic events involved in this process remai...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.4.541
更新日期:1995-04-01 00:00:00
abstract::At birth, virtually all peripheral CD8(+) T cells express the CD28 co-stimulatory molecule, but healthy human adults accumulate CD28(-)CD8(+) T cells that often express the CD57 marker. While these CD28(-) subpopulations are known to exert effector-type functions, the generation, maintenance and regulation of CD28(-) ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.8.1327
更新日期:1999-08-01 00:00:00
abstract::The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/7.9.1425
更新日期:1995-09-01 00:00:00
abstract::Secretory IgA (sIgA) antibodies in human tears and milk were found to recognize protein disulfide isomerase (PDI) on a Toxoplasma gondii lysate immunoblot (IB). These antibodies were already detectable in tears of infants. To determine the epitope containing-regions on PDI, we generated truncated versions of recombina...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxf091
更新日期:2002-11-01 00:00:00
abstract::It is now generally recognized that bone marrow is the survival niche for antigen-specific plasma cells with long-term immunological memory. These cells release antibodies into the circulation, needed to prime effector cells in the secondary immune response. These antibodies participate in the surveillance for antigen...
journal_title:International immunology
pub_type: 杂志文章,评审
doi:10.1093/intimm/dxy048
更新日期:2018-08-30 00:00:00
abstract::Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A bot...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxv014
更新日期:2015-09-01 00:00:00
abstract::Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/8.6.905
更新日期:1996-06-01 00:00:00
abstract::Long-term side effects may represent a relevant burden of antiretroviral treatment (ART) in HIV-infected patients with good CD4 immune reconstitution over extended time spans. CD4-guided treatment interruption (TI) has been evaluated to address this point and may result in a wide spectrum of time off ART in different ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxq462
更新日期:2011-02-01 00:00:00
abstract::Dendritic cells (DC) are potent antigen-presenting cells and understanding their mechanisms of antigen uptake is important for loading DC with antigen for immunotherapy. The multilectin receptors, DEC-205 and macrophage mannose receptor (MMR), are potential antigen-uptake receptors; therefore, we examined their expres...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.11.1511
更新日期:2000-11-01 00:00:00
abstract::CD4 T cells are not thought to play a significant role in generating an effective primary CD8 T cell response to most viral infections. We have challenged this view by demonstrating that antigen-specific CD4 T cells can indeed suppress the proliferation of antigen-specific naive CD8 T cells in response to low doses of...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxl061
更新日期:2006-08-01 00:00:00
abstract::Oral administration of large doses of protein antigen generally induces a state of systemic unresponsiveness currently termed mucosally induced tolerance. In this study, we used human milk protein (HMP) without casein as a multi-protein antigen for the study of mucosally induced tolerance. The HMP utilized in this stu...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.4.537
更新日期:1998-04-01 00:00:00
abstract::Soluble recombinant (r) P-selectin and rP-selectin immobilized on plastic surfaces were tested for their capacity to activate neutrophils to produce superoxide anion. Soluble rP-selectin was incapable of activating leukocytes, whereas immobilized rP-selectin was able to induce leukocyte activation. When neutrophils we...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/12.4.487
更新日期:2000-04-01 00:00:00
abstract::CT1 is a carbohydrate moiety of CD45 that is expressed on fetal thymocytes in vivo. Examination of CT1 expression on thymocyte subsets revealed that primarily pro-T cells (CD44+ CD25+) and pre-T cells (CD44- CD25+) expressed CT1. Interestingly, non-T-lineage committed lymphoid progenitors (CD44+ CD25-) lacked CT1 indi...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.4.445
更新日期:1998-04-01 00:00:00
abstract::NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing beta cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice i...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.6.957
更新日期:1999-06-01 00:00:00
abstract::HLA-B*0702 transgenic mice (expressing a chimeric heavy chain with a murine alpha 3 domain: HLA-B7(m alpha 3)) in which the H-2K(b) and H-2D(b) class I-a (Cl I-a(-/-)) genes have been inactivated were compared with H-2K(b)D(b) Cl I-a(+/+) positive controls. Expression of the HLA-B7(m alpha 3) molecules resulted in a 3...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxg073
更新日期:2003-06-01 00:00:00
abstract::The two-signal model states that activation of naive T cells requires a signal 1 stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1 alone is sufficient for pre-activated T cells. Recently, however, it has been shown that under certain conditions T cells can bypass the requirement for co-stim...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.5.619
更新日期:1998-05-01 00:00:00
abstract::J11d is expressed on a variety of hemopoietic cells, including B cells. In previous studies, we have shown that B cells are heterogeneous with respect to their levels of J11d expression and that memory B cells are contained within the J11dlo B cell population. In this report, we have further examined the relationship ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/4.6.691
更新日期:1992-06-01 00:00:00
abstract::The TCR complex transduces the antigen recognition signal through common activation motifs present in both CD3 gamma delta epsilon chains and zeta dimers within the complex. We have investigated functional roles of the cytoplasmic domain in zeta and CD3 gamma delta epsilon for T cell activation in early and late respo...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/6.11.1671
更新日期:1994-11-01 00:00:00
abstract::Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ T cells expressing TCR alphabeta. In the present study, we compared characteristics between CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/11.1.21
更新日期:1999-01-01 00:00:00
abstract::Natural killer (NK) cells are a major FcγRIIIA-expressing lymphocyte population that mediate antibody-dependent cellular cytotoxicity. Although NK cells are critical for immunity against viruses and tumors, they are also activated in the joints of patients with rheumatoid arthritis (RA) and may be involved in disease ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxz010
更新日期:2019-04-26 00:00:00
abstract::The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase ...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/dxn009
更新日期:2008-04-01 00:00:00
abstract::Dendritic cells (DC) are highly potent activators of the immune response. The precise mechanisms that give rise to the DC phenotype are not known. To investigate the mechanisms that contribute to the generation of the DC phenotype, precursor DC were freshly isolated from human blood and allowed to mature in vitro. The...
journal_title:International immunology
pub_type: 杂志文章
doi:10.1093/intimm/10.11.1713
更新日期:1998-11-01 00:00:00