Abstract:
:Genome-wide association studies (GWAS) have revolutionized the search for genetic influences on complex disorders, such as primary biliary cirrhosis (PBC). Recent GWAS have identified many disease-associated genetic variants. These, overall, highlighted the remarkable contribution of key immunological pathways in PBC that may be involved in the initial mechanisms of loss of tolerance and the subsequent inflammatory response and chronic bile duct damage. Results from GWAS have the potential to be translated in biological knowledge and, hopefully, clinical application. There are a number of immune pathways highlighted in GWAS that may have therapeutic implications in PBC and in other autoimmune diseases, such as the anti-interleukin-12/interleukin-23, nuclear factor-kb, tumor necrosis factor, phosphatidylinositol signaling and hedgehog signaling pathways. Further areas in which GWAS findings are leading to clinical applications either in PBC or in other autoimmune conditions, include disease classification, risk prediction and drug development. In this review we outline the possible next steps that may help accelerate progress from genetic studies to the biological knowledge that would guide the development of predictive, preventive, or therapeutic measures in PBC.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Carbone M,Lleo A,Sandford RN,Invernizzi Pdoi
10.1002/eji.201344270subject
Has Abstractpub_date
2014-04-01 00:00:00pages
945-54issue
4eissn
0014-2980issn
1521-4141journal_volume
44pub_type
杂志文章,评审abstract::X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease in man, characterized by an arrest in B lymphocyte differentiation at the precursor B cell stage. The structure of expressed immunoglobulin (Ig) kappa light (L) chain rearrangements of nine B lymphoblastoid cell lines from one XLA patient was inve...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230306
更新日期:1993-03-01 00:00:00
abstract::Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. These proteins are encoded by mutated genes which may also give rise to truncated membrane immunoglobulins. The neoplastic cells proliferate in vivo although they can...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830211110
更新日期:1991-11-01 00:00:00
abstract::The present study tests whether the specific inhibition of helper T (Th) cell (and T hybridomas) by suppressor T (Ts) cells is a phenotypic trait of Th cells correlating with their acquired specificity for antigen/major histocompatibility complex or a genotypic trait not related to selection of the T cell repertoire f...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830180415
更新日期:1988-04-01 00:00:00
abstract::Chlamydia pneumoniae stimulates potently maturation of and cytokine secretion by bone marrow-derived dendritic cells (BMDDC). BMDDC responses depend mainly on Toll-like receptor (TLR)2 and to a minor extent on TLR4. We demonstrate here using C. pneumoniae in an infectious model with the replication-permissive epitheli...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200209)32:9<2460::AID-IMMU2460>3
更新日期:2002-09-01 00:00:00
abstract::T-cell death is a fundamental process that is intricately regulated at multiple phases during T-cell differentiation, tolerance induction and the decline of the immune response. Caspase 3 is a crucial molecule regulating both mitochondrial and death receptor apoptotic pathways and therefore we were interested in exami...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201040475
更新日期:2010-12-01 00:00:00
abstract::Majority of HIV-2-infected individuals meet the criteria of long-term non-progressors. This has been linked to superior qualitative HIV-2-specific cellular immune responses that correlate with viral control. However, it is unknown whether this is due to frequent targeting of immunodominant Gag epitopes in HIV-2 than H...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200838759
更新日期:2008-12-01 00:00:00
abstract::The effector function of activated CD4(+) T cells and secretion of cytokines are important in the establishment of productive immune responses and tolerance. We identified expression by CD4(+) T cells of Notch receptors and ligands and enhanced Notch signaling upon activation. Notch1 expression was up regulated and co...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425562
更新日期:2005-03-01 00:00:00
abstract::An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and lymphokine-activated killer (LAK) cells is secreted by CD8+CD57+ T lymphocytes, a subset expanded during infection with HIV and after bone marrow transplantation. We...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830241145
更新日期:1994-11-01 00:00:00
abstract::The role of monocytes, B cells, and adherent and nonadherent T cells in the response of purified protein derivative of tuberculin (PPD) as measured by [3H]thymidine uptake in vitro has been explored. The response to PPD was found to be highly dependent on monocytes, to approximately the same extent as previously found...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830090411
更新日期:1979-04-01 00:00:00
abstract::Btk is a member of the Tec family of protein tyrosine kinases expressed in B cells. It is stimulated following cross-linking of the B cell receptor which leads to the autophosphorylation of a specific residue in the SH3 domain, Y223. Previous work using Btk-derived fusion proteins has shown that the Btk SH3 domain bin...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199907)29:07<2269::AID-IMM
更新日期:1999-07-01 00:00:00
abstract::The lymph node cells (LNC) activated in vivo by liver regeneration following partial hepatectomy of mice (primed lymph node cells) respond to regenerating liver cells in vitro with typical secondary immune response characteristics (Miyahara, S. et al., Eur. J. Immunol. 1983. 13: 878). These LNC activated in vivo suppr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830131105
更新日期:1983-11-01 00:00:00
abstract::B cell development in organ cultures of fetal liver from mice at day 14 of gestation resembles in kinetics and cell numbers generated the one observed in vivo. This development in vitro can be blocked by an IL-7 receptor-specific monoclonal antibody. Monoclonal antibodies specific for the pre-B cell receptor, i. e. fo...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200003)30:3<759::AID-IMMU759>3.0
更新日期:2000-03-01 00:00:00
abstract::Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200838809
更新日期:2009-03-01 00:00:00
abstract::In the present study, we have investigated the anatomic distribution and the function of different populations of HIV-1- and cytomegalovirus (CMV)-specific memory CD8 T cells. The different populations of virus-specific memory CD8 T cells were distinguished on the basis of the expression of CD45RA and CCR7, and the co...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200212)32:12<3756::AID-IMMU3756>
更新日期:2002-12-01 00:00:00
abstract::Cycling lymphocytes may express the enzyme telomerase which is involved in maintenance of telomere length and cell proliferation potential. In CD8(+) T cells freshly isolated from peripheral blood, we found that in vivo cycling cells expressed HLA-DR. Furthermore, CD28-positive cells are known to have longer telomeres...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200102)31:2<459::aid-immu459>3.0
更新日期:2001-02-01 00:00:00
abstract::Cells in homeostasis metabolize glucose mainly through the tricarboxylic acid cycle and oxidative phosphorylation, while activated cells switch their basal metabolism to aerobic glycolysis. In this study, we examined whether metabolic reprogramming toward aerobic glycolysis is important for the host response to Mycoba...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201546259
更新日期:2016-11-01 00:00:00
abstract::Dendritic cells (DC) play the dual task of initiating cellular immunity against potentially harmful foreign antigens (Ag), while maintaining immunological tolerance to self-Ag and environmental Ag. As an approach to induce Ag-specific suppression, we and others introduced CD95 ligand (L) cDNA into DC. The resulting "k...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200204)32:4<1035::AID-IMMU1035>3
更新日期:2002-04-01 00:00:00
abstract::In vivo, T cells expressing low-affinity TCR predominate in primary, but not in secondary responses, a process referred to as T cell affinity maturation. Using CD4 dependence as a measure of the avidity of the interaction between the allospecific TCR and the alloantigen, we show that a similar process occurs in mixed ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200102)31:2<646::aid-immu646>3.0
更新日期:2001-02-01 00:00:00
abstract::Human T cell clones (TCC) are antigen-presenting cells (APC) able to present peptides and superantigens (SAg) and to process and present intact proteins. TCC express major histocompatibility complex (MHC) class II antigens and molecules involved in the accessory signal delivery, such as B7.1 and B7.2/B70. Notwithstand...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830260411
更新日期:1996-04-01 00:00:00
abstract::Analysis of mice transgenic for immunoglobulin genes should allow definition of the cis-acting DNA sequences required to target somatic mutation to antibody V genes. We have looked for mutations in a chimeric kappa transgene encoding a V region specific for the hapten 2-phenyloxazolone (phOx) linked to a rat C kappa g...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830200625
更新日期:1990-06-01 00:00:00
abstract::The thymus provides the microenvironment in which thymocytes develop into mature T cells, and interactions with thymic stromal cells are thought to provide the necessary signals for thymocyte maturation. Recognition of self-MHC by T cells is a basic requirement for mature T-cell functions, and those thymocytes that do...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.201142338
更新日期:2012-07-01 00:00:00
abstract::Polyclonal differentiation of unprimed B cells into IgM-producing cells induced by lipopolysaccharide (LPS) or T cell-derived lymphokine B151-TRF2 has been shown to contain a process of I-A-restricted B-B cell interaction, so that the B cell responses are inhibited by monoclonal antibodies (mAb) specific for I-A molec...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830191208
更新日期:1989-12-01 00:00:00
abstract::In a search for proteins involved in signal transduction through the T cell receptor (TcR/CD3 complex), a recently developed highly efficient method for labeling of nucleotide binding proteins in permeabilized cells was applied. Here, we report that human CD3-gamma could be labeled by periodate-oxidized [alpha-32P] GT...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230224
更新日期:1993-02-01 00:00:00
abstract::Cholera toxin (CT) can function as a potent adjuvant in the mucosal immune response. However, we have found that treatment of A20-HL murine B lymphoma cells with CT severely inhibits the presentation of ovalbumin (OVA) to cells of the T cell clone 42-6A specific for OVA(323-339)/I-Ad, whereas it does not affect the pr...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199905)29:05<1561::AID-IMM
更新日期:1999-05-01 00:00:00
abstract::PA28alpha/beta is a regulatory complex of the 20S proteasome which consists of two IFN-gamma inducible subunits. Both subunits, alpha and beta, contribute equally to the formation of hexa- or heptameric rings which can associate with the 20S proteasome. Previously, we have shown that overexpression of the PA28alpha su...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200012)30:12<3672::AID-IMMU3672>
更新日期:2000-12-01 00:00:00
abstract::Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after i...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201243084
更新日期:2013-08-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830221143
更新日期:1992-11-01 00:00:00
abstract::Natural killer (NK) cell activity can be stimulated by different surface receptors. 2B4 is a member of the signaling lymphocyte activation molecule (SLAM)-related receptor family and is important for stimulating human NK cell cytotoxicity and cytokine production. Here we show that stimulation of human NK cells by anti...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200636146
更新日期:2006-12-01 00:00:00
abstract::IL-23, a proximal regulator of IL-17, may be a major driving force in the induction of autoimmune inflammation. We have used a model of subdiabetogenic treatment with multiple low doses of streptozotocin (MLD-STZ; 4 x 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated beta cell ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200535325
更新日期:2006-01-01 00:00:00
abstract::As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C(+) NK cells reported in other infectious diseases is systematically associated with HCMV co-...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.201243117
更新日期:2013-05-01 00:00:00