BACKGROUND.: The goal of this study was to determine whether antidonor antibodies directed against human leukocyte antigen (HLA) or endothelial cells (ECs) expressed antigens, including major histocompatibility complex class I chain-related antigens A (MICA) are associated with the diagnosis of antibody-mediated rejection (AMR) in heart transplant recipients. METHODS.: We studied ...

HLA alloimmunization induced by pregnancy, multiple transfusions or transplantation is responsible for some of the serious complications seen in patients receiving blood and blood products. These complications are primarily the result of antibody and antigen triggering an acute immunological reaction, which in some cases can be fatal e.g. TRALI. Some ...

Malignant transformation of cells is often associated with changes in classical and non-classical HLA class I antigen, HLA class II antigen as well as NK cell activating ligand (NKCAL) expression. These changes are believed to play a role in the clinical course of the disease since these molecules are critical ...

BACKGROUND: HLA-G in biological fluids has been proposed to be useful as a tumor marker as both a diagnostic and prognostic factor. Most HLA-G measurement procedures are based on ELISA methods using highly specific antibodies. However, results of published studies are in conflict regarding the clinical utility and even the ...

BACKGROUND.: ABO and human leukocyte antigen (HLA) alloantibodies provide major immunologic barriers to successful transplantation; however, there is increasing recognition for the role of anti-endothelial cell antibodies (AECAs) in allograft rejection. We investigated the relationship between AECAs identified using donor-derived endothelial cell precursors (ECPs) and kidney allograft rejection and function. ...

OBJECTIVE: Recent data suggest that a gene-environment interaction exists between smoking and the HLA SE alleles in shaping the autoimmune reaction towards specific citrullinated antigens. Here, we determined the effects of HLA SE alleles and TE (Tobacco Exposure) on the immune response against various citrullinated antigens. These associations were analyzed ...

Interferons-β (IFN-β) are the most widely used immunomodulatory drugs for treatment of multiple sclerosis (MS). The development of neutralizing antibodies (NABs) against IFN-β is one of the main reasons for treatment failure. While formulation of the drug has a proven impact on the development of NABs, the genetic predisposition to ...

Histocompatibility testing has been used in support of solid organ and hematopoietic stem cell transplantation for over fifty years and transplantation has clearly served as a major stimulus for interest in the human major histocompatibility complex, the HLA system. Until the 1990s, typing and definition of antibodies to HLA antigens ...

Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all ...

Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most important factors influencing graft survival after renal transplantation. PRA is generally analyzed with enzyme-linked immunosorbent assay or flow cytometry (FC), which identify the HLA antigen specific for the preformed antibody. We tested 66 patients for FC crossmatch (FCXM) ...

BACKGROUND: We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI. STUDY DESIGN AND METHODS: In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of ...

Antibodies against allogeneic human leukocyte antigen (HLA) molecules are important impediments to the success of different clinical procedures including transplantation and platelet transfusion. In these settings, characterization of the repertoire of immunogenic epitopes is important for permissible mismatch determination and the identification of acceptable mismatches for sensitized patients. HLAMatchmaker is ...

Pre-transplant screening of a female with ESRD showed no anti-HLA alloantibodies by AHG-CDC (Class I) or ELISA (Class II). Following a negative AHG-CDC crossmatch, an HLA*01:01+ DD kidney was transplanted in 09/05. Subsequent screening of pre-txplt serum by LABScreen® Single Antigen (SA) array showed strong reactivity vs. A*01:01. Despite that ...

The purpose of the study was to compare three different methods defining donor-specific antibodies (DSA): complement-dependent cytotoxicity (CDC), the flow cytometry method (FCM), and a special for that purpose commercially available Luminex-based solid phase assay (SPA). A panel of human monoclonal antibodies (HuMabs) with well-defined human leukocyte antigen (HLA) specificities ...

Mostly indirect evidence suggests an important pathogenic role for non-HLA anti-endothelial cell antibodies (AECAs) in both acute and chronic rejection. The lack of standardized screening assays for AECAs unfortunately hampers the systematic collection of data in multicenter trials. Diagnostic tests based on commercially available platforms could pave the way for ...

The downregulation of human leukocyte antigen class I (HLA-I) has been proposed to contribute to the immune evasion of cancer cells in some cancers. Meanwhile, transcriptional silencing by means of promoter methylation is now believed to be an important mechanism of carcinogenesis. The aim of this study was (1) to ...

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related deaths. Donor HLA antibodies have been implicated in TRALI cases. Blood centers are implementing TRALI risk reduction strategies based on HLA antibody screening of some subpopulations of ever-pregnant apheresis platelet (PLT) donors. However, if screening assay cutoffs are ...

It has been confirmed that defective expression of human leukocyte antigen class I (HLA-I) molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class I antigen and the antigen-processing machinery (APM) components ...

The risk for developing celiac disease is associated with the major histocompatibility complex class II human leukocyte antigen DQ2 and DQ8. We retrospectively reviewed the medical records of 127 consecutive cases of adult-onset celiac disease evaluated at a single United States center to determine the distribution of the associated human ...

The new alleles human leukocyte antigen (HLA)-B*40:122 and HLA-B*40:127 differs from B*40:02:01 and B*40:06:01:01 by a single nucleotide, respectively.

We have shown previously that human leukocyte antigen (HLA) class I immunogenicity can be predicted by the number, position, and physiochemical differences of polymorphic amino acids (AAs). We have now modeled the structural and physiochemical polymorphisms of HLA class II alloantigens and correlated these with humoral alloimmunity in sensitized patients ...

Flow cytometric analysis of leukocyte surface antigens has been used to characterize infectious and septic processes in patients. We wanted to investigate how the sampling and processing temperature, the anticoagulant used, and the storage of the sample influence leukocyte immunophenotyping. Four blood samples, two using acid citrate dextrose and two ...

We reviewed HLA antibody testing results using an enzyme-linked immunosorbent assay (ELISA) for all male blood donors at our institution during a 3.5-month period to look for HLA immunization. Confirmatory testing of 33 blood samples positive for HLA class I and/or II antibodies was performed using the fluorescent bead method. ...

Kidney transplant recipients exhibiting antibodies (Ab) against either HLA or non-HLA antigens undergo frequent episodes of rejection and exhibit decreased long-term graft survival. The novel flow cytometry crossmatch kit XM-ONE, detects Abs to HLA antigens plus those directed to Tie-2-positive precursor endothelial cells (anti-endothelial cell antibodies, AECA). We studied the ...

BACKGROUND: Although HLA-C matching is not considered in kidney transplantation, several reports have shown that anti-HLA-C antibodies are associated with rejection and graft failure. DNA-based typing methods can now accurately determine HLA-C compatibility and sensitive assays such as Luminex with single alleles can identify HLA-C antibodies. HLA-C displays considerable amino ...

PURPOSE: To investigate variations in expression of the monocyte antigen presentation molecule HLA-DR in cirrhosis. METHODS: HLA-DR expression was measured by flow cytometry in 100 patients within 48 h of admission and repeated a week later in 21 patients admitted to ICU. IL-10, TNF-α and IFN-γ secretion in response to lipopolysaccharide ...

A pilot study of anti-human leukocyte antigen (HLA)-DR monoclonal antibody (mAb) in dogs with lymphoma was undertaken to verify the suitability of a canine model to address therapeutically relevant endpoints prior to a full trial in dogs, and ultimately human investigation. In vitro studies demonstrated that L243, a murine IgG1 ...

In pregnant women, circulating alloantibodies, triggered by exposure to paternal HLA antigens, are frequently detectable. The finding of lower alloantibody levels in women who experience spontaneous abortion (miscarriage) has led to the speculation that antipaternal antibodies could favor maintenance of pregnancy, whereas their lack poses a risk of miscarriage. Postulating ...

Etiologies of Renal Cell Carcinoma (RCC) are not clear despite of the fact that many risk factors have been suggested. Especially in high stages RCC can affect the immune system in various ways. Human Leukocyte Antigens (HLA) may play a complementary role in the activation between the tumor and immunity. ...

Previous population-based, genetic studies have shown that human leukocyte antigen (HLA) class II loci such as HLA-DR4 (DRB1*04) and HLA-DR14 (DRB1*14) alleles are consistently associated with the occurrence of pemphigus vulgaris (PV) in Japanese as well as other ethnic populations. Among PV-related HLA-DRB1 alleles (*0406, *1401, *1405, *1406) in Japan, ...

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are of special interest in immunology because of their potent inhibitory function. Many fundamental aspects of Tregs, including their antigenic profile, development and peripheral homeostasis, remain highly controversial. Here, we propose a Treg-centered antigen-non-specific immunoregulation model focused on the T-cell system, particularly on CD4(+) T ...

Systemic immune tolerance is induced for orally administered antigen, and this phenomenon is called oral tolerance. However, the mechanism of oral tolerance has not been completely elucidated. It has been suggested that antigen presentation and generation of regulatory T cells in Peyer's patches (PPs) are important for induction of oral ...

Ultrafine nanoparticles of zinc oxide (ZnO) recently became available as a substitute for larger-size fine ZnO particles. However, the biological activity of ultrafine ZnO currently remains undefined. In the present study, we investigated the effect of ultrafine ZnO on oral tolerance that plays an important role in the prevention of ...

Allergic asthma is a chronic lung disease resulting from an inappropriate T helper (Th)-2 response to environmental antigens. Early tolerance induction is an attractive approach for primary prevention of asthma. Here, we found that breastfeeding by antigen-sensitized mothers exposed to antigen aerosols during lactation induced a robust and long-lasting antigen-specific ...

Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the "two-signal" model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for ...

We previously showed that incorporating target sequences for the hematopoietic-specific microRNA miR-142 into an antigen-encoding transgene prevents antigen expression in antigen-presenting cells (APCs). To determine whether this approach induces immunologic tolerance, we treated mice with a miR-142-regulated lentiviral vector encoding green fluorescent protein (GFP), and subsequently vaccinated the mice against ...

BACKGROUND: Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction ...

Exposure to noninherited maternal antigens (NIMAs) in fetal and neonatal life has life-long immunological consequences. Although there is a plethora of evidence of effects of mother on the immune responses of her offspring, there is very little knowledge available on how exposure to NIMA can result in either tolerance or ...

Successful factor (F) VIII replacement therapy in hemophilia A patients is confounded by the generation of inhibitory anti-FVIII antibodies (Ab) in 25-30% of treated patients. These antibodies, termed 'inhibitors', significantly increase morbidity within the hemophilia population and lower the quality of life for these patients. For the past 30 years, ...

For more than 2 centuries active immunotherapy has been at the forefront of efforts to prevent infectious disease [Waldmann TA (2003) Nat Med 9:269-277]. However, the decreased ability of the immune system to mount a robust immune response to self-antigens has made it more difficult to generate therapeutic vaccines against ...

BACKGROUND: The purpose of this work was to investigate the effects of early low-level exposure to either antigen or antibody alone on subsequent immune responses in entirely immunologically naïve animals. This is impossible in species with a permeable placenta such as rodents or humans, where both antigen and antibody can ...

Pretreatment of Lewis rats with soluble mycobacterial Hsp65 affords protection against subsequent adjuvant-induced arthritis (AIA). This study was aimed at unraveling the mechanisms underlying mycobacterial Hsp65-induced protection against arthritis, using contemporary parameters of immunity. Lewis rats were given 3 intraperitoneal injections of mycobacterial Hsp65 in solution prior to the initiation ...

Oral tolerance inhibits T-cell dependent reactions to antigens previously contacted by oral route. Parenteral re-exposure to orally-tolerated antigens inhibits immune responses to unrelated antigens, a phenomenon we have called "indirect effects" of oral tolerance. We examined the requirements of previous irradiation of C57BL/6 and BALB/c recipients to successful transfer of ...

To study B-cell tolerance against non-lymphoid tissue autoantigens, we generated transgenic rat insulin promoter (RIP)-OVA/hen egg lysozyme (HEL) mice expressing the model antigens, OVA and HEL, in pancreatic islets. Their vaccination with OVA or HEL induced far less auto-Ab titers compared with non-transgenic controls. Depletion of CD25(+) cells during immunization ...

Regulatory T lymphocytes (Tregs) are specialized for immune suppression and are important regulators of the immune response in various settings. Tregs actively suppress enteroantigen-reactive cells and contribute to the maintenance of intestinal immune homeostasis. Distinct Treg subsets coexist in the intestinal mucosa and mesenteric lymph nodes. Disturbances in Treg number ...

Rubella virus (RV) is an enveloped, positive sense, single stranded RNA virus in the family Togaviridae. The virus consists of a host derived lipid bilayer membrane, two trans-membrane proteins E1 and E2, and the C protein which together with viral RNA forms the icosahedral nucleocapsid. RV causes natural infections in ...

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC-E2) leads to an anti-mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our ...

PROBLEM: Alterations in RCAS1 (a receptor-binding cancer antigen expressed on SiSo cells) expression in the placenta and decidua may be related to the regulation of the process of maternal immune tolerance against fetal antigens. Moreover, it has been demonstrated that the occurrence of the spontaneous beginning of stillbirth is related ...

An effective adaptive immune response requires the prior induction of the regulatory effector T-helper (eTh). There are two competing models of how this cell is induced to effectors. Under the Associative Recognition of Antigen (ARA) or "two signal" model, the T-helper requires eTh in order to be induced to eTh, ...

Mechanisms involved in the induction of oral tolerance (OT) or systemic immunization through the oral rout are still poorly understood. In our previous studies, we have shown that when normal mice eat peanuts they become tolerant, with no gut alterations. Conversely, if immunized with peanut proteins prior to a challenge ...