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Minoo Battiwalla - One of the best experts on this subject based on the ideXlab platform.
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Human leukocyte antigen DR4 is associated with inferior progression-free survival following allogeneic hematopoietic stem cell transplantation for lymphoid malignancies
Leukemia & lymphoma, 2008Co-Authors: Charu Aggarwal, Sameer Gupta, Theresa Hahn, Shannon Smiley, Padmanabhan, Philip L. Mccarthy, Minoo BattiwallaAbstract:The Class II human leukocyte antigen (HLA) DRB1 antigen DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-lymphoproliferative disorders. We retrospectively reviewed the role of HLA DR4 on outcomes in 77 related and 22 unrelated consecutive first HLA-matched alloHSCT patients with lymphoid malignancies treated between 1992 and 2003. HLA DRB1 typing was determined by molecular (n = 69) or serologic (n = 30) methods. The proportion of patients with one HLA DR4 antigen was 18% (18/99). At a median follow-up of 5.6 years, there were no significant differences in aGvHD, cGvHD and OS between the HLA DR4 positive versus negative patients in any disease or donor subgroups. Nine of 18 (50%) DR4 positive patients and 20 of 81 (25%) DR4 negative patients had disease progression post HSCT (p = 0.033). Progression-free survival (PFS) at 3 years was 29% in the DR4 positive group and 70% in the DR4 negative group (p = 0.004). In univariate and multivariate analyses, DR4 posit...
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Human leukocyte antigen (HLA) DR4 is associated with inferior progression free survival (PFS) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for lymphoid malignancies
Journal of Clinical Oncology, 2006Co-Authors: Charu Aggarwal, Sameer Gupta, Theresa Hahn, Philip L. Mccarthy, Swaminathan Padmanabhan, Minoo BattiwallaAbstract:6543 Background: HLA DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We investigated the HLA DR4 role on graft-versus-host disease (GVHD) and graft-versus-leukemia effect in HLA-matched HSCT performed for lymphoid malignancies. Methods: We retrospectively reviewed 77 related and 22 unrelated consecutive allo HSCT patients (pts) treated between 1992 and 2003 at RPCI to investigate the influence of HLA DR4 on overall survival (OS), PFS and grade 2–4 acute and chronic GVHD (cGVHD) incidence. HLA DR B1 typing was determined by molecular (n=69) or serologic (n=30) methods. The pt proportion with one or two HLA DR4 antigens was 18% (18/99), similar to the general Caucasian population. Pt characteristics included: ALL (n=41), CLL (n=4), HD (n=7) and NHL (n=47); median age 36 y (range 6–64); Male (n=65), Female (n=34); Caucasian (>95%); Total Body Irradiation (TBI) conditioning regimens (n=79); Busu...
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Human leukocyte antigen (HLA) DR4 is not associated with differences in overall survival (OS), progression free survival (PFS), or graft-vs-host-disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for myeloid malig
Journal of Clinical Oncology, 2006Co-Authors: Sameer Gupta, Charu Aggarwal, Theresa Hahn, Philip L. Mccarthy, Swaminathan Padmanabhan, Minoo BattiwallaAbstract:6552 Background: HLA DR4 is associated with autoimmune disorders and with response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We have earlier reported association of DR 15 positivity with decreased acute GVHD (aGVHD) in patients undergoing allo HSCT for myeloid malignancies (Blood, 2005 Nov 10;Epub). Therefore we investigated the role of HLA DR4 on graft-versus-leukemia effect and GVHD in HLA-matched allo HSCT performed for myeloid malignancies. Methods: A retrospective review of 119 consecutive related and 48 consecutive unrelated allo HSCT patients (pts) treated between 1992 and 2003 at RPCI was performed to investigate the influence of HLA DR4 on OS, PFS and the incidence of grade 2–4 aGVHD and chronic GVHD (cGVHD). HLA DR B1 locus typing was determined by either molecular (n=108) or serologic (n=59) methods. The proportion of patients with one or two HLA DR4 antigens was 26% (43/167) which is similar to the range seen in general Caucasian...
Thomas G. Forsthuber - One of the best experts on this subject based on the ideXlab platform.
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A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice
Vaccine, 2013Co-Authors: Ashlesh K Murthy, Thomas G. Forsthuber, James P Chambers, M. Neal Guentzel, Guangming Zhong, Gopala Krishna Koundinya Lanka, Senthilnath Lakshmana Chetty, Bernard P ArulanandamAbstract:Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has been shown to provide robust protection against genital Chlamydia infection. Adoptive transfer of IFN-γ competent CPAF-specific CD4⁺ T cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient IFN-γ-deficient mice indicating the importance of IFN-γ secreting CD4⁺ T cells in host defense against Chlamydia. In this study, we identify CD4⁺ T cell reactive CPAF epitopes and characterize the activation of epitope-specific CD4⁺ T cells following antigen immunization or Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for screening overlapping peptides that induced T cell IFN-γ production, we identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex. Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing these 5 epitopes induced a robust cell-mediated immune response and significantly accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep vaccination induced CPAF-specific CD4⁺ T cells in the spleen were detected using HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4⁺ clones could be detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia trachomatis strain challenge using these novel tetramers. These results provide the first direct evidence that a novel CPAF epitope vaccine can provide protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope-specific CD4⁺ T cells in HLA-DR4 mice following C. muridarum or C. trachomatis infection. Such tetramers could be a useful tool for monitoring CD4⁺ T cells in immunity to Chlamydia infection and in developing epitope-based human vaccines using the murine model.
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francisella tularensis t cell antigen identification using humanized hla dr4 transgenic mice
Clinical and Vaccine Immunology, 2010Co-Authors: Tatareddy Goluguri, Thomas G. Forsthuber, Neal M Guentzel, James P Chambers, Ashlesh K Murthy, Karl E Klose, Bernard P ArulanandamAbstract:There is no licensed vaccine against the intracellular pathogen Francisella tularensis. The use of conventional mouse strains to screen protective vaccine antigens may be problematic, given the differences in the major histocompatibility complex (MHC) binding properties between murine and human antigen-presenting cells. We used engineered humanized mice that lack endogenous MHC class II alleles but that express a human HLA allele (HLA-DR4 transgenic [tg] mice) to identify potential subunit vaccine candidates. Specifically, we applied a biochemical and immunological screening approach with bioinformatics to select putative F. tularensis subsp. novicida T-cell-reactive antigens using humanized HLA-DR4 tg mice. Cell wall- and membrane-associated proteins were extracted with Triton X-114 detergent and were separated by fractionation with a Rotofor apparatus and whole-gel elution. A series of proteins were identified from fractions that stimulated antigen-specific gamma interferon (IFN-gamma) production, and these were further downselected by the use of bioinformatics and HLA-DR4 binding algorithms. We further examined the validity of this combinatorial approach with one of the identified proteins, a 19-kDa Francisella tularensis outer membrane protein (designated Francisella outer membrane protein B [FopB]; FTN_0119). FopB was shown to be a T-cell antigen by a specific IFN-gamma recall assay with purified CD4(+) T cells from F. tularensis subsp. novicida DeltaiglC-primed HLA-DR4 tg mice and cells of a human B-cell line expressing HLA-DR4 (DRB1*0401) functioning as antigen-presenting cells. Intranasal immunization of HLA-DR4 tg mice with the single antigen FopB conferred significant protection against lethal pulmonary challenge with an F. tularensis subsp. holarctica live vaccine strain. These results demonstrate the value of combining functional biochemical and immunological screening with humanized HLA-DR4 tg mice to map HLA-DR4-restricted Francisella CD4(+) T-cell epitopes.
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Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele.
Infection and immunity, 2006Co-Authors: Ashlesh K Murthy, Thomas G. Forsthuber, Yu Cong, Cathi Murphey, M. Neal Guentzel, Guangming Zhong, Bernard P ArulanandamAbstract:There is no licensed vaccine available against Chlamydia trachomatis, the leading cause of bacterial sexually transmitted disease. We have found that intranasal immunization with recombinant chlamydial protease-like activity factor (CPAF) induces CD4+ T-cell- and gamma interferon (IFN-γ)-dependent protective immunity against murine genital chlamydial infection, thus making CPAF a viable vaccine candidate for further characterization. HLA-DR4 is the predominant allele involved in chlamydial antigen presentation to CD4+ T cells in humans. We used engineered mice that lack endogenous major histocompatibility complex class II (MHC-II) alleles but express a human HLA allele (HLA-DR4 transgenic [tg] mice) to examine primary immune and CPAF-mediated responses against genital Chlamydia muridarum challenge. Upon primary bacterial exposure, HLA-DR4 tg mice developed Chlamydia-specific IFN-γ and antibody production and resolved the infection within 30 days, similar to challenged conventional C57BL/6 animals. Moreover, C. muridarum-challenged HLA-DR4 tg mice exhibited CPAF-specific antibody and IFN-γ production. Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg animals exhibited robust CPAF-specific IFN-γ production and elevated titers of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of IgG2b and IgG1 antibodies. HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus IL-12 resolved the primary genital chlamydial infection significantly earlier than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient mice displayed minimal antigen-specific immune responses and failed to resolve the infection even at 30 days postchallenge. Together, these results demonstrate the importance of human HLA-DR4 molecules in the recognition and presentation of CPAF epitopes, leading to the generation of protective antichlamydial immunity and making these mice a valuable model for mapping HLA-DR4-restricted chlamydial epitopes.
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T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis.
Clinical immunology (Orlando Fla.), 2004Co-Authors: Juliane Klehmet, Carey L. Shive, Edward G. Spack, Robert Weissert, Rocio Guardia-wolff, Ines Petersen, Bernhard O. Boehm, Thomas G. ForsthuberAbstract:Abstract Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97–108 (MOG 97–108 ; TCFFRDHSYQEE), the T cell response diversifies over time to MOG 181–200 (core: MOG 183–191 ; FVIVPVLGP) and MBP. The spreading epitope MOG 181–200 binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in “humanized” HLA-DR4 transgenic mice.
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T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells
Journal of immunology (Baltimore Md. : 1950), 2001Co-Authors: Thomas G. Forsthuber, Carey L. Shive, Wolfgang Wienhold, Katrien L. De Graaf, Edward G. Spack, Robert Sublett, Arthur Melms, Jens J. Kort, Michael K. Racke, Robert WeissertAbstract:Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS). In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients. Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG. The data indicated that MOG peptide 97-108 (core 99-107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice. Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS.
Bernard P Arulanandam - One of the best experts on this subject based on the ideXlab platform.
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A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice
Vaccine, 2013Co-Authors: Ashlesh K Murthy, Thomas G. Forsthuber, James P Chambers, M. Neal Guentzel, Guangming Zhong, Gopala Krishna Koundinya Lanka, Senthilnath Lakshmana Chetty, Bernard P ArulanandamAbstract:Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has been shown to provide robust protection against genital Chlamydia infection. Adoptive transfer of IFN-γ competent CPAF-specific CD4⁺ T cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient IFN-γ-deficient mice indicating the importance of IFN-γ secreting CD4⁺ T cells in host defense against Chlamydia. In this study, we identify CD4⁺ T cell reactive CPAF epitopes and characterize the activation of epitope-specific CD4⁺ T cells following antigen immunization or Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for screening overlapping peptides that induced T cell IFN-γ production, we identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex. Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing these 5 epitopes induced a robust cell-mediated immune response and significantly accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep vaccination induced CPAF-specific CD4⁺ T cells in the spleen were detected using HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4⁺ clones could be detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia trachomatis strain challenge using these novel tetramers. These results provide the first direct evidence that a novel CPAF epitope vaccine can provide protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope-specific CD4⁺ T cells in HLA-DR4 mice following C. muridarum or C. trachomatis infection. Such tetramers could be a useful tool for monitoring CD4⁺ T cells in immunity to Chlamydia infection and in developing epitope-based human vaccines using the murine model.
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francisella tularensis t cell antigen identification using humanized hla dr4 transgenic mice
Clinical and Vaccine Immunology, 2010Co-Authors: Tatareddy Goluguri, Thomas G. Forsthuber, Neal M Guentzel, James P Chambers, Ashlesh K Murthy, Karl E Klose, Bernard P ArulanandamAbstract:There is no licensed vaccine against the intracellular pathogen Francisella tularensis. The use of conventional mouse strains to screen protective vaccine antigens may be problematic, given the differences in the major histocompatibility complex (MHC) binding properties between murine and human antigen-presenting cells. We used engineered humanized mice that lack endogenous MHC class II alleles but that express a human HLA allele (HLA-DR4 transgenic [tg] mice) to identify potential subunit vaccine candidates. Specifically, we applied a biochemical and immunological screening approach with bioinformatics to select putative F. tularensis subsp. novicida T-cell-reactive antigens using humanized HLA-DR4 tg mice. Cell wall- and membrane-associated proteins were extracted with Triton X-114 detergent and were separated by fractionation with a Rotofor apparatus and whole-gel elution. A series of proteins were identified from fractions that stimulated antigen-specific gamma interferon (IFN-gamma) production, and these were further downselected by the use of bioinformatics and HLA-DR4 binding algorithms. We further examined the validity of this combinatorial approach with one of the identified proteins, a 19-kDa Francisella tularensis outer membrane protein (designated Francisella outer membrane protein B [FopB]; FTN_0119). FopB was shown to be a T-cell antigen by a specific IFN-gamma recall assay with purified CD4(+) T cells from F. tularensis subsp. novicida DeltaiglC-primed HLA-DR4 tg mice and cells of a human B-cell line expressing HLA-DR4 (DRB1*0401) functioning as antigen-presenting cells. Intranasal immunization of HLA-DR4 tg mice with the single antigen FopB conferred significant protection against lethal pulmonary challenge with an F. tularensis subsp. holarctica live vaccine strain. These results demonstrate the value of combining functional biochemical and immunological screening with humanized HLA-DR4 tg mice to map HLA-DR4-restricted Francisella CD4(+) T-cell epitopes.
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Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele.
Infection and immunity, 2006Co-Authors: Ashlesh K Murthy, Thomas G. Forsthuber, Yu Cong, Cathi Murphey, M. Neal Guentzel, Guangming Zhong, Bernard P ArulanandamAbstract:There is no licensed vaccine available against Chlamydia trachomatis, the leading cause of bacterial sexually transmitted disease. We have found that intranasal immunization with recombinant chlamydial protease-like activity factor (CPAF) induces CD4+ T-cell- and gamma interferon (IFN-γ)-dependent protective immunity against murine genital chlamydial infection, thus making CPAF a viable vaccine candidate for further characterization. HLA-DR4 is the predominant allele involved in chlamydial antigen presentation to CD4+ T cells in humans. We used engineered mice that lack endogenous major histocompatibility complex class II (MHC-II) alleles but express a human HLA allele (HLA-DR4 transgenic [tg] mice) to examine primary immune and CPAF-mediated responses against genital Chlamydia muridarum challenge. Upon primary bacterial exposure, HLA-DR4 tg mice developed Chlamydia-specific IFN-γ and antibody production and resolved the infection within 30 days, similar to challenged conventional C57BL/6 animals. Moreover, C. muridarum-challenged HLA-DR4 tg mice exhibited CPAF-specific antibody and IFN-γ production. Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg animals exhibited robust CPAF-specific IFN-γ production and elevated titers of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of IgG2b and IgG1 antibodies. HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus IL-12 resolved the primary genital chlamydial infection significantly earlier than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient mice displayed minimal antigen-specific immune responses and failed to resolve the infection even at 30 days postchallenge. Together, these results demonstrate the importance of human HLA-DR4 molecules in the recognition and presentation of CPAF epitopes, leading to the generation of protective antichlamydial immunity and making these mice a valuable model for mapping HLA-DR4-restricted chlamydial epitopes.
Charu Aggarwal - One of the best experts on this subject based on the ideXlab platform.
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Human leukocyte antigen DR4 is associated with inferior progression-free survival following allogeneic hematopoietic stem cell transplantation for lymphoid malignancies
Leukemia & lymphoma, 2008Co-Authors: Charu Aggarwal, Sameer Gupta, Theresa Hahn, Shannon Smiley, Padmanabhan, Philip L. Mccarthy, Minoo BattiwallaAbstract:The Class II human leukocyte antigen (HLA) DRB1 antigen DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-lymphoproliferative disorders. We retrospectively reviewed the role of HLA DR4 on outcomes in 77 related and 22 unrelated consecutive first HLA-matched alloHSCT patients with lymphoid malignancies treated between 1992 and 2003. HLA DRB1 typing was determined by molecular (n = 69) or serologic (n = 30) methods. The proportion of patients with one HLA DR4 antigen was 18% (18/99). At a median follow-up of 5.6 years, there were no significant differences in aGvHD, cGvHD and OS between the HLA DR4 positive versus negative patients in any disease or donor subgroups. Nine of 18 (50%) DR4 positive patients and 20 of 81 (25%) DR4 negative patients had disease progression post HSCT (p = 0.033). Progression-free survival (PFS) at 3 years was 29% in the DR4 positive group and 70% in the DR4 negative group (p = 0.004). In univariate and multivariate analyses, DR4 posit...
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Human leukocyte antigen (HLA) DR4 is associated with inferior progression free survival (PFS) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for lymphoid malignancies
Journal of Clinical Oncology, 2006Co-Authors: Charu Aggarwal, Sameer Gupta, Theresa Hahn, Philip L. Mccarthy, Swaminathan Padmanabhan, Minoo BattiwallaAbstract:6543 Background: HLA DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We investigated the HLA DR4 role on graft-versus-host disease (GVHD) and graft-versus-leukemia effect in HLA-matched HSCT performed for lymphoid malignancies. Methods: We retrospectively reviewed 77 related and 22 unrelated consecutive allo HSCT patients (pts) treated between 1992 and 2003 at RPCI to investigate the influence of HLA DR4 on overall survival (OS), PFS and grade 2–4 acute and chronic GVHD (cGVHD) incidence. HLA DR B1 typing was determined by molecular (n=69) or serologic (n=30) methods. The pt proportion with one or two HLA DR4 antigens was 18% (18/99), similar to the general Caucasian population. Pt characteristics included: ALL (n=41), CLL (n=4), HD (n=7) and NHL (n=47); median age 36 y (range 6–64); Male (n=65), Female (n=34); Caucasian (>95%); Total Body Irradiation (TBI) conditioning regimens (n=79); Busu...
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Human leukocyte antigen (HLA) DR4 is not associated with differences in overall survival (OS), progression free survival (PFS), or graft-vs-host-disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for myeloid malig
Journal of Clinical Oncology, 2006Co-Authors: Sameer Gupta, Charu Aggarwal, Theresa Hahn, Philip L. Mccarthy, Swaminathan Padmanabhan, Minoo BattiwallaAbstract:6552 Background: HLA DR4 is associated with autoimmune disorders and with response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We have earlier reported association of DR 15 positivity with decreased acute GVHD (aGVHD) in patients undergoing allo HSCT for myeloid malignancies (Blood, 2005 Nov 10;Epub). Therefore we investigated the role of HLA DR4 on graft-versus-leukemia effect and GVHD in HLA-matched allo HSCT performed for myeloid malignancies. Methods: A retrospective review of 119 consecutive related and 48 consecutive unrelated allo HSCT patients (pts) treated between 1992 and 2003 at RPCI was performed to investigate the influence of HLA DR4 on OS, PFS and the incidence of grade 2–4 aGVHD and chronic GVHD (cGVHD). HLA DR B1 locus typing was determined by either molecular (n=108) or serologic (n=59) methods. The proportion of patients with one or two HLA DR4 antigens was 26% (43/167) which is similar to the range seen in general Caucasian...
S. Breanndan Moore - One of the best experts on this subject based on the ideXlab platform.
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Clinical and HLA phenotypes of type 1 autoimmune hepatitis in North American patients outside DR3 and DR4.
Liver International, 2006Co-Authors: Albert J Czaja, Herschel A Carpenter, S. Breanndan MooreAbstract:AIMS: To determine the clinical phenotype and outcome of patients with definite type 1 autoimmune hepatitis, who lack human leukocyte antigen (HLA) DR3 and DR4, and to assess the importance of HLA DR7 and DR13. METHODS: Two hundred and seven adult patients were typed for DR3, DR4, DR7, and DR13 by DNA-based techniques. One hundred and two blood donors constituted a normal population. RESULTS: Twenty-six patients lacked DR3 and DR4 (13%). Treatment failure occurred more commonly in these individuals than in the 68 patients with DR4 (20% vs. 3%, P = 0.03), and relapse after drug withdrawal was less frequent than in the 84 patients with DR3 (55% vs. 87%, P = 0.03). HLA DR13 occurred more often than in those with DR3 (54% vs. 15%, P = 0.0002) or DR4 (54% vs. 12%, P = 0.00005), and it was more frequent than in normal adults (54% vs. 22%, P = 0.003), including those without DR3 or DR4 (54% vs. 27%, P = 0.03). HLA DR7 was not associated with susceptibility or outcome. CONCLUSIONS: White North American patients who lack DR3 and DR4 respond differently to corticosteroid treatment than patients with classical HLA phenotypes. HLA DR13 is common in these adult patients, and it may affect treatment outcome.
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Significance of HLA DR4 in type 1 autoimmune hepatitis
Gastroenterology, 1993Co-Authors: Albert J Czaja, Herschel A Carpenter, Paula J. Santrach, S. Breanndan MooreAbstract:Abstract Background: HLA DR3 and DR4 have been recognized as independent risk factors for autoimmune hepatitis. We compared the clinical features and prognosis of patients with HLA DR4 to those with HLA DR3 and other phenotypes to determine if subclassification by HLA is a valid consideration. Methods: Forty-four patients with HLA DR4; 41 patienfs with HLA DR3; and 16 patients with neither allele were studied. Ninety patients were treated with corticosteroids. Results: Patients with HLA DR4 were older (51 ± 2 years vs. 38 ± 3 years, P = 0.0001) and more commonly women (89% vs. 68%, P = 0.04) than counterparts with HLA DR3. Additionally, these patients had higher serum immunoglobulin G levels (3300 ± 216 mg/dL vs. 2732 ± 192 mg/dL, P = 0.05) and a greater frequency of concurrent immunologie diseases (59% vs. 27%, P = 0.005). Similar differences in clinical presentation distinguished the patients with HLA DR4 from those with other phenotypes. Remission duringcorticosteroid therapy (85% vs. 63%, P = 0.05) occurred more commonly in the patients with HLA DR4 than in those with HLA DR3 and treatment failure (10% vs. 32%, P = 0.03) occurred less frequently. Conclusions: Patients with HLA DR4 have a different clinical profile than counterparts with other phenotypes, and they have a better response to corticosteroid therapy than patients with HLA DR3. Subclassification of patients by HLA DR phenotype may have clinical and prognostic value.
