Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Major Histocompatibility Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed1986

Ia+ murine epidermal Langerhans cells are deficient in surface expression of the class I major histocompatibility complex.

Murine epidermal Langerhans cells were analyzed with fluorescence microscopy and multicolor flow cytometry for the surface expression of major histocompatibility complex (MHC) class I and class II antigens. Langerhans cells of H-2k haplotype were identified in situ or in epidermal-cell suspensions by their surface expression of the MHC class II determinants I-Ak and I-Ek. More than 90% of class II-positive Langerhans cells in epidermal-cell suspensions expressed no or barely detectable amounts of MHC class I antigens. Quantitation by flow cytometry revealed that H-2k Langerhans cells expressed only 1.6-3.3% as much H-2Kk as did class II-negative keratinocytes in the same epidermal-cell suspensions. By fluorescence microscopy, class I MHC antigens were not detectable on Langerhans cells in situ when analyzed on sheets of intact epidermis. The deficient expression of class I MHC permitted highly purified Langerhans cell populations to be isolated from epidermal cell suspensions by treatment with anti-class I MHC monoclonal antibody and complement. It is likely that the uniquely low cell-surface expression of class I MHC antigen by Langerhans cells has relevance to both immune responses in the skin as well as to mechanisms of skin allograft rejection. In addition, it is conceivable that regulation of class I MHC expression on antigen-presenting cells in general is an important but hitherto unrecognized mechanism of immune regulation.

Animals↗
PubMed1988

Morphologic studies of acute rat cardiac allograft rejection across an isolated major histocompatibility complex class I (RT1A) disparity.

To define the morphologic correlates of acute rat cardiac allograft rejection across an isolated major histocompatibility complex (MHC) class I disparity, rejecting PVG.R1 cardiac allografts transplanted to (PVG x WF)F1 recipients were studied from days 4-8 posttransplantation. Documented ultrastructural tracer techniques as well as immunohistologic and immunoelectron microscopic methods were employed for morphologic analysis. Using intravenously administered horseradish peroxidase as a tracer probe for cell membrane permeability dysfunction, it was shown that severe diffuse loss of integrity of the microvascular endothelium preceded functional rejection, providing strong evidence that the allograft microcirculation is a central target of graft destruction. Also, rejection was associated with localized cardiac myofiber alterations prior to development of significant endothelial changes, indicating that cardiac muscle cells are additional cellular targets of immunologic injury. The ultrastructural features of progressive endothelial and myofiber injury, the predominance of MRC OX8+ lymphocytes and MRC OX6+ macrophages sequestered within the grafts, and the pattern of donor class I expression by allograft endothelium and cardiac myofibers were similar to those observed in rejecting allografts in full MHC-disparate combinations. Since it has been previously shown that MRC OX8+ class I-reactive T cells are absolutely required for rejection in this isolated class I-disparate model, the morphologic data raise the possibility that the OX8+ T lymphocyte subpopulation may also play a highly significant role in rat cardiac allograft rejection across a full MHC disparity.

Animals↗
PubMed1991

Expression of CD4 in transgenic mice alters the specificity of CD8 cells for allogeneic major histocompatibility complex.

We have generated a transgenic mouse line in which a CD4 transgene is expressed on a significant fraction of the mature CD8+ lymphocytes but is not expressed in the thymus. This provides an opportunity to examine the functional consequences of CD4 expression in a population of class I-selected CD8+ lymphocytes. CD8+ lymphocytes expressing the CD4 transgene proliferate in response to allogeneic class I and class II major histocompatibility complex, whereas CD8+ cells from control animals proliferate only to allogeneic class I gene products. These observations suggest that the ability of a T-cell population to react with class II allogeneic major histocompatibility complex is determined by the presence of CD4.

Animals↗
PubMed1993

Activation with superantigens induces programmed death in antigen-primed CD4+ class II+ major histocompatibility complex T lymphocytes via a CD11a/CD18-dependent mechanism.

Staphylococcal enterotoxin superantigens (SAg) bind class II major histocompatibility complex (MHC) molecules on antigen-presenting cells (APC) and upon cell-to-cell contact stimulate proliferation of T cells expressing appropriate V beta gene products. In addition, SAg can also deliver negative signals to Ag-specific T cells resulting in a state of unresponsiveness or a loss of viability. The present study examines the functional consequences of a direct interaction of SAg with alloAg-specific class II MHC+ CD4+ T cell lines (TCL). Our results demonstrate that SAg induce programmed death (apoptosis) in a majority of Ag-specific CD4+ T cells accompanied by genomic DNA fragmentation. SAg binding to Ag-specific TCL resulted in a rapid mobilization of intracellular free calcium ([Ca2+]i) and transcription of a number of cytokine genes including interleukin-2(IL-2), IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granzyme B indicating the activation of primed T cells. Both SAg-induced cytokine gene expression as well as subsequent death were significantly inhibited by a tyrosine kinase inhibitor herbimycin A and also by cyclosporin A. SAg-induced death of primed T cells was also inhibited by monoclonal antibodies (mAb) directed at the CD11a/CD18 molecule but not those reactive with other T cell surface molecules such as CD2, CD7, CD28, CD29 or CD49d. None of these mAb, including anti-CD11a/CD18, had any effect on SAg-induced expression of IL-2 and IL-4 genes or SAg-induced [Ca2+]i response. Addition of cytokines such as IL-1 alpha, IL-2, IL-4, IL-6, GM-CSF, IFN-gamma, tumor necrosis factor (TNF-alpha, or TNF-beta), or neutralizing Ab to these cytokines had no effect on SAg-induced death of Ag-specific TCL. The T cells which survived the death-inducing effects of SAg showed down-regulation of the CD3/T cell receptor and up-regulation of CD2 and HLA-DR expression, and upon re-exposure to the same SAg upregulated expression of mRNA for IL-2 and IFN-gamma. Presentation of SAg by B7+ ICAM-1+ LFA-3+ DR+ professional APC was also able to induce the death of Ag-specific TCL. Together these results suggest that the activation with SAg causes programmed death of Ag-specific TCL cells via a mechanism that requires late participation of the CD11a/CD18 molecule.

Antigens, Bacterial↗
PubMed1989

[Molecular analysis of mouse major histocompatibility complex class I gene expression of tumors growing in the brain].

The authors have investigated the regulation of mouse major histocompatibility complex (MHC, H-2) class I gene expression of tumors growing in the brain, by using T-cell lymphoma (Moloney leukemia virus-induced YAC-1 of A/Sn mouse origin) and its cell surface H-2 negative variants, A. H-2- and beta 2m-. FACS analysis showed that low H-2 expressing YAC-1 markedly increased H-2 Kk, Dd and beta-2 microglobulin (beta 2m) induction on the cell surface after intracerebral (i.c.) passage, while there was no change in phenotypical expression of both A. H-2- and beta 2m-. Southern and Northern blot analyses revealed that the enhancement of H-2 class I expression in YAC-1 was due to transcriptional control of H-2 DNA genes. beta 2m- was confirmed to lack beta 2m- gene, causing cell surface H-2 negative expression. Immunoprecipitation method showed that, despite increase in mRNA of the H-2 gene, A. H-2- disclosed no class I H-2 expression because of the incapability of intracellular association of polypeptides between H-2 and beta 2m in the post-translational level. The H-2 class I expression on YAC-1 cells could also be induced by interferon gamma (IFN) in a dose-dependent manner in the range of 1 to 100 U/ml. At 100 U/ml, the H-2 inducing effect, regulated at the transcriptional level, was comparable to that observed after i.c. passage. In contrast, the A. H-2- and beta 2m- remained completely negative after IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

The genomic sequence and comparative analysis of the rat major histocompatibility complex.

We have determined the sequence of a 4-Mb interval on rat chromosome 20p12 that encompasses the rat major histocompatibility complex (MHC). This is the first report of a finished sequence for a segment of the rat genome and constitutes one of the largest contiguous sequences thus far for rodent genomes in general. The rat MHC is, next to the human MHC, the second mammalian MHC sequenced to completion. Our analysis has resulted in the identification of at least 220 genes located within the sequenced interval. Although gene content and order are well conserved in the class II and class III gene intervals as well as the framework gene regions, profound rat-specific features were encountered within the class I gene regions, in comparison to human and mouse. Class I region-associated differences were found both at the structural level, the number, and organization of class I genes and gene families, and, in a more global context, in the way that evolution worked to shape the present-day rat MHC.

Animals↗
PubMed1988

Allorecognition of purified major histocompatibility complex glycoproteins by cytotoxic T lymphocytes.

To investigate how T cells recognize allogeneic class I proteins encoded by the major histocompatibility complex (MHC), we examined the human cytotoxic T lymphocytes (CTL) elicited in a mixed lymphocyte reaction against a lymphoblastoid B-cell line (JY) whose MHC-class I proteins are HLA-A2 and -B7. By panning the responding T cells on plates that were coated with purified HLA-A2, an essentially pure population of CD8+ anti-HLA-A2 CTL was isolated in a single step and established as a cell line designated A2p. In addition to lysing HLA-A2+ target cells, the A2p cells lysed HLA-A2- cells, including mouse cells (P815), when purified native HLA-A2 was attached to them, but not when denatured HLA-A2 was attached. Thus, contrary to the general rule that T cells recognize sequential antigenic determinants in denatured protein antigens, the alloreactive CTLs appear to recognize determinants that depend upon the native configuration of HLA-A2; however, the possibility that these T cells recognize a peptide adduct persistently associated with purified, soluble HLA-A2 has not been ruled out.

Animals↗
PubMedDate not supplied

Infectious diseases and immunity: special reference to major histocompatibility complex.

Human leukocyte antigens (HLAs) are an inherent system of alloantigens, which are the products of genes of the major histocompatibility complex (MHC). These genes span a region of approximately 4 centimorgans on the short arm of human chromosome 6 at band p 21.3 and encode the HLA class I and class II antigens, which play a central role in cell-to-cell interaction in the immune system. These antigens interact with the antigen-specific cell surface receptors of T lymphocytes (TCR) thus causing activation of the lymphocytes and the resulting immune response. Class I antigens restrict cytotoxic T-cell (CD8+) function thus killing viral infected targets, while class II antigens are involved in presentation of exogenous antigens to T-helper cells (CD4+) by antigen presenting cells (APC). The APC processes the antigens, and the immunogenic peptide is then presented at the cell surface along with the MHC molecule for recognition by the TCR. Since the MHC molecules play a central role in regulating the immune response, they may have an important role in controlling resistance and susceptibility to diseases. In this review we have highlighted studies conducted to look for an association between HLA and infectious diseases; such studies have had a variable degree of success because the pathogenesis of different diseases varies widely, and most diseases have a polygenic etiology.

Alleles↗
PubMed1997

The major histocompatability complex (MHC) contains conserved polymorphic genomic sequences that are shuffled by recombination to form ethnic-specific haplotypes.

The major histocompatibility complex (MHC) consists of polymorphic frozen blocks (PFBs) that are linked to form megabase haplotypes. These blocks consist of polymorphic sequences and define regions where recombination appears to be inhibited. We have been able to show, using a highly polymorphic sequence centromeric of HLA-B (within the beta block), that PFBs are conserved and contain specific insertions/deletions and substitutions that are the same for individuals with the same MHC haplotype but that differ between at least most different haplotypes. A sequence comparison between ethnic-specific haplotypes shows that these sequences have remained stable and predate the formation of these haplotypes. To determine whether the same conserved block has been involved in the generation of multiple haplotypes, we compared the block typing profiles of different ethnic specific haplotypes. Block typing profiles have previously been shown to be identical in individuals with the same MHC haplotype but, generally, to differ between different haplotypes. It was found that some PFBs are common to more than one haplotype, implying a common ancestry. Subsequently, haplotypes have been generated by the shuffling and exchange of these PFBs. The regions between these PFBs appear to permit the recombination sites and therefore could be expected to exhibit either low polymorphism or a localized "hotspot."

Asian People↗
PubMed1990

Immunopathological factors in peripheral nerve allograft rejection: quantification of lymphocyte invasion and major histocompatibility complex expression.

The numbers of helper T and cytotoxic T lymphocytes and macrophages were quantified, and the expression of major histocompatibility complex (MHC) class I and class II molecules was examined in rat peripheral nerve allografts from 1 to 14 days after implantation, using the indirect immunoperoxidase method for light and electron microscopy. Two centimetre segments of peripheral nerve freshly obtained from inbred Dark Agouti strain rats were inserted in a gap created in n. fibularis or n. tibialis of young adult inbred Wistar strain rats, using fascicular nerve repair techniques under general anaesthesia. There was a gradual increase in the number of helper T and cytotoxic/suppressor T cells from day 2 with peak numbers of both types of T cells observed around day 7. The results suggest that the critical time for T cell proliferation is between day 6 and day 7 post-operatively. The number of macrophages increased over 10 days, with peak numbers being observed at day 10 post-operatively. This is in accord with the pattern of rejection observed in allografts of other tissue. Schwann cells were found to express MHC class I and class II molecules by day 2 post-operatively, which is well before there is any substantial T cell and macrophage infiltration. It may be that the donor Schwann cells act as antigen presenting cells, triggering the immune response and finally becoming a target of the rejection process.

Animals↗
PubMed1998

Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE.

OBJECTIVE: To investigate the predisposing role of major histocompatibility complex (MHC) genes to autoantibody production and clinical manifestations comparing French Canadian and Non-French Canadian Caucasians with systemic lupus erythematosus (SLE) METHODS: Ninety-one Caucasian patients with SLE were studied. Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing) were determined. RESULTS: Photosensitivity was present in all SLE subjects with anti-Ro antibodies (P=0.001, RR=13.1, CI=1.8, 564). Photosensitivity was further associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A gene deletion was associated with anti-Ro (P=0.008, RR=4.6, CI=1.4, 16.2) and anti-La (P=0.02, RR=11.7, CI=1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P=0.01, RR=21.3, CI=1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P=0.02, RR=0.3, CI=0.07, 0.8) and correlated with HLA-DR15 (P=0.006, RR=4.2, CI=1.5, 12.8) and Dw2 (P=0.009, RR=3.9, CI=1.4, 11.9). CONCLUSION: C4A gene deletion has a previously unrecognized powerful association with anti-Ro and anti-La autoantibodies. These results support the concept of divergent MHC gene associations with autoantibody expression and emphasize the influence of ethnicity on the immunogenetic study of SLE.

Adult↗
PubMed1996

Excess admixture proportion of extended major histocompatability complex haplotypes of Caucasian origin among rheumatoid arthritis associated haplotypes in African Americans and Afro-Caribbeans.

Several extended major histocompatability complex (MHC) haplotypes are associated with susceptibility to autoimmune disease in Caucasian populations. It is known that African Americans and Afro-Caribbeans are ethnic groups descended from west, central and southern black African populations which are admixed with Caucasians. To examine the possible association of some marker of Caucasian MHC genes and susceptibility to rheumatoid arthritis (RA) in African Americans, we studied extended MHC haplotypes (HLA-B, complement and DR) in a sample of 18 African American and Afro-Caribbean probands with RA, their first degree relatives and in 15 non-RA families. We defined 36 disease-associated RA haplotypes among the probands and 96 normal haplotypes in normal individuals. To obtain the most conservative estimate, we excluded recognized Caucasian, DR4-bearing, extended MHC haplotypes from the analysis. Admixture proportions for non-HLA-DR4 extended MHC haplotypes of known Caucasian origin among RA-associated and normal haplotypes were computed (0.40 versus 0.163 respectively). When we compared the difference in proportions between RA and normal haplotypes, the proportion of extended MHC haplotypes of known Caucasian origin was significantly increased among RA-associated haplotypes (Z = 3.16, p (one sided) < 0.001, p (adjusted) < 0.008). Our results suggest that racial admixture with Caucasian MHC genes may augment RA susceptibility and thus may be one mechanism to explain the higher prevalence of RA in African Americans and Afro-Caribbeans than in black African populations.

Arthritis, Rheumatoid↗
PubMed1989

A monoclonal antibody to LFA-3, the CD2 ligand, specifically immobilizes major histocompatibility complex proteins.

T cells are activated when the antigen-specific T cell receptor recognizes antigen in association with major histocompatibility complex (MHC) proteins. The T cell surface protein CD2 (T11, LFA-2, the T erythrocyte receptor) and its target or stimulator cell ligand, lymphocyte function-associated antigen-3 (LFA-3), are also involved in T cell adhesion and activation. The molecular mechanisms by which the CD2/LFA-3 interaction affects T cell adhesion and activation are unclear. The CD2/LFA-3 interaction may be modeled by the interaction between LFA-3 and anti-LFA-3 monoclonal antibody (mAb). We used the fluorescence photobleaching recovery technique to investigate the effect of anti-LFA-3 mAb on the lateral mobility of MHC proteins in plasma membranes of JY, a human Epstein-Barr virus-transformed B cell line. Anti-LFA-3 mAb induced immobilization of class I MHC proteins labeled with bivalent but not monovalent fluorescein-conjugated W6/32 mAb. Anti-LFA-3 mAb also caused immobilization of class II MHC proteins labeled with bivalent fluoresceinated LB3.1 mAb. In contrast, anti-LFA-3 mAb did not affect the mobilities of either a B cell membrane protein labeled with bivalent fluoresceinated anti-CD45 (human leukocyte antigen) mAb or a membrane lipid analogue. Unlike anti-LFA-3 mAb, anti-LFA-1 mAb did not affect class I MHC protein mobility. These results suggest that CD2 binding to LFA-3 may trigger a physiological response in which target cell MHC proteins, cross-linked by receptors on the T cell surface, are immobilized at and thereby localized to the T cell-target cell interface.

Antibodies, Monoclonal↗
PubMed1993

The major histocompatibility complex influences myelin basic protein 63-88-induced T cell cytokine profile and experimental autoimmune encephalomyelitis.

Polymorphism of the major histocompatibility complex (MHC) influences susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP) in rats. Current concepts relate such influences to the capacity of class II molecules to present relevant peptides to autoreactive T cells. We have here analyzed the MHC influence on the immune response and the development of EAE after immunization with the immunodominant peptide MBP-63-88. Analysis of MHC-congenic LEWIS strains showed that RT1a, RT1c and RT1(1) haplotypes are permissive for disease induction, whereas RT1d and RT1u are resistant. All EAE responding strains showed peptide-specific proliferation and interferon (IFN)-gamma secretion, but no early significant tendency to express interleukin (IL-4) or transforming growth factor (TGF)-beta mRNA in lymphocytes in response to the MBP 63-88, 7 days post immunization (p.i.). Later, 14 days p.i., peptide-specific induction of IL-4 and TGF-beta occurred in RT1(1) rats. Among the EAE non-responders strains, only the RT1u rats showed an immune response to MBP 63-88. This response, however, was qualitatively different from the immune response in the EAE-susceptible strains. Thus, there was no proliferation and only moderate IFN-gamma production in response to peptide, but in contrast, a significant and early peptide-induced IL-4 and TGF-beta response was observed. The data suggest that the MHC-associated susceptibility to EAE is partly related to the ability to mount a TH1-like immune response while the MHC-associated EAE resistance may either be related to MBP peptide non-responsiveness or to peptide recognition and induction of a qualitatively different and disease down-regulatory immune response.

Amino Acid Sequence↗
PubMed1993

Faulty major histocompatibility complex class II I-E expression is associated with autoimmunity in diverse strains of mice. Autoantibodies, insulitis, and sialadenitis.

Many regions and loci of the murine genome contribute to the pancreatic and salivary gland autoimmunity observed in the diabetic NOD mouse. Examination of the major histocompatibility complex region of the NOD mouse has revealed a defect in the expression of the major histocompatibility complex class II gene, I-E. To determine the isolated role of faulty I-E expression in abnormal self-recognition, we examined six commonly used inbred strains of mice on diverse genetic backgrounds that also do not express I-E, i.e., C57BL/10, SJL, ACA, DBA/1, NOD, and 129. Autoimmunity was assessed by the presence of inflammatory cell infiltrates (0,+/-,+,++, , +) within and among the pancreatic islets and salivary glands, and autoantibodies to self determinants. At 6 mo of age, inflammatory infiltrates in the pancreas (0, 3 mice; +/-, 3 mice; +, 7 mice; ++, 6 mice; , 1 mouse; +, 5 mice) and/or salivary glands (0, 0 mice; +/-, 3 mice; +, 1 mouse; ++, 4 mice; , 6 mice; +, 10 mice) were detected as well as autoantibodies in all 24 mice of all I-E- mouse strains on diverse genetic backgrounds. This indicates that defective expression of this single locus, in isolation, is sufficient for the spontaneous development of autoreactivity. In contrast, the simultaneous examination of 19 I-E+ mice on five commonly used inbred strains of mice (BALB/c, C67/KsJ, B10.BR, B10.A [2R], and B10.A [5R]) demonstrated no signs of humoral or cellular autoimmunity with target gland destruction or lymphocytic invasion. Our data suggest that many commonly used inbred strains of mice represent models of autoimmunity attributable to this single defective gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The major histocompatibility complex and diseases in farm animals.

Breeding for genetic resistance to disease and development of veterinary vaccines are major stimuli for research of the major histocompatibility complex (MHC) in farm animals. Genetically determined resistance is an attractive preventive measure because it precludes veterinary services, and is consistent over generations. Also many infectious diseases in farm animals cannot be prevented by vaccination. In a recent seminar sponsored by the European Community, the MHC of farm animals was discussed, its association with diseases was assessed, and other means of selection for disease resistance were evaluated.

Animal Diseases↗
PubMed1999

A new liquid chromatography/tandem mass spectrometric approach for the identification of class I major histocompatibility complex associated peptides that eliminates the need for bioassays.

Cell-surface class I major histocompatibility complex (MHC) molecules present processed self- and nonself-peptides to thymus-derived (T) lymphocytes, allowing the intracellular compartment of cells to be sampled in order to detect infection. Since the class I MHC-peptide complex plays a critical role in cell-mediated immunity, it is important to obtain sequence information on the MHC-associated peptides unique to infected cells as a prelude to the development of vaccines. Here, we outline and test an alternative strategy for identifying the proteins that are processed through the MHC pathway. This new strategy eliminates the necessity of developing and maintaining cytotoxic T lymphocyte (CTL) lines for peptide identification. In this new approach genome sequences from the infecting agent are scanned for stretches of amino acids that match a particular MHC binding motif. Molecular masses from these putative MHC-binding peptide sequences are calculated and compared to those found for peptides isolated from pathogen-infected host cells using liquid chromatography/mass spectrometry (LC/MS). Peptides with masses matching those in the database are then analyzed by tandem mass spectrometry (MS/MS) to determine their identity. Using this approach we were able to confirm the processing and presentation of two Trypanosoma cruzi proteins by the MHC class I pathway. These data suggest that a rigorous approach employing two-dimensional separations in conjunction with MS/MS and bioinformatics is a feasible means of identifying pathogen gene products of immunological interest when a CTL assay is unavailable or unsuccessful.

Animals↗
PubMed2004

Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients.

OBJECTIVE: To determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA). METHODS: Seventy-eight infliximab-treated patients with RA were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, MHC class I chain-related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA-B-associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi-square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers. RESULTS: Among responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status. CONCLUSION: The data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.

Adult↗