High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anaemia patients: a reliable marker of immune‐mediated aplastic anaemia responsive to cyclosporine therapy
To better characterize immunologic aberrations in aplastic anaemia (AA), we examined peripheral blood mononuclear cells (PBMC) of 67 patients with AA and other patients with various haematological diseases for the expression of heat shock protein 72 (hsp72), which is inducible in lymphocytes by vari...
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Veröffentlicht in: | British journal of haematology 1999-08, Vol.106 (2), p.377-384 |
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creator | Takami, Akiyoshi Nakao, Shinji Tatsumi, Yasuaki Wang, Hongbo Weihua, Zeng Yamazaki, Hirohito Yasue, Shizuka Shiobara, Shintaro Matsuda, Tamotsu Mizoguchi, Hideaki |
description | To better characterize immunologic aberrations in aplastic anaemia (AA), we examined peripheral blood mononuclear cells (PBMC) of 67 patients with AA and other patients with various haematological diseases for the expression of heat shock protein 72 (hsp72), which is inducible in lymphocytes by various stressors including antigenic stimulation. When freshly obtained PBMC were examined using flow cytometry, the proportion of cells expressing hsp72 in cytoplasm was significantly higher in allogeneic marrow transplant recipients (22 ± 15%, mean ±standard deviation (SD)) and AA patients (17 ± 21%) than in normal individuals (6 ± 3%). When PBMC were tested after heat treatment, only the proportion of hsp72+ cells of AA patients (37 ± 30%) was significantly higher than that of the normal control (17 ± 11%). Dual fluorescence analysis of the PBMC revealed that the majority of hsp72+ cells was CD3+. For 28 untreated AA patients, the proportion of hsp72+ cells in those who later responded to cyclosporine (CyA) (62 ± 24%) was higher than that in non‐responders (19 ± 13%). Immunoblotting analysis revealed predominant expression of hsp72 in T cells. These findings indicate that high inducibility of hsp72 in PBMC by heat treatment is an immunologic aberration characteristic of CyA‐responsive AA and that this simple test may be useful for identifying a subset of AA patients responsive to immunosuppressive therapy. |
doi_str_mv | 10.1046/j.1365-2141.1999.01540.x |
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When freshly obtained PBMC were examined using flow cytometry, the proportion of cells expressing hsp72 in cytoplasm was significantly higher in allogeneic marrow transplant recipients (22 ± 15%, mean ±standard deviation (SD)) and AA patients (17 ± 21%) than in normal individuals (6 ± 3%). When PBMC were tested after heat treatment, only the proportion of hsp72+ cells of AA patients (37 ± 30%) was significantly higher than that of the normal control (17 ± 11%). Dual fluorescence analysis of the PBMC revealed that the majority of hsp72+ cells was CD3+. For 28 untreated AA patients, the proportion of hsp72+ cells in those who later responded to cyclosporine (CyA) (62 ± 24%) was higher than that in non‐responders (19 ± 13%). Immunoblotting analysis revealed predominant expression of hsp72 in T cells. These findings indicate that high inducibility of hsp72 in PBMC by heat treatment is an immunologic aberration characteristic of CyA‐responsive AA and that this simple test may be useful for identifying a subset of AA patients responsive to immunosuppressive therapy.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.1999.01540.x</identifier><identifier>PMID: 10460594</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, U.K. and Cambridge, USA: Blackwell Science Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic - drug therapy ; Anemia, Aplastic - metabolism ; aplastic anaemia ; Biological and medical sciences ; Biomarkers ; Child ; Cyclosporine - therapeutic use ; cyclosporine A ; Female ; Flow Cytometry ; heat shock protein 72 ; Heat-Shock Proteins - metabolism ; HSP72 Heat-Shock Proteins ; Humans ; Immunoblotting ; Immunomodulators ; Immunosuppressive Agents - therapeutic use ; Leukocytes, Mononuclear - immunology ; Lymphocyte Activation ; Male ; Medical sciences ; Middle Aged ; Pharmacology. 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When freshly obtained PBMC were examined using flow cytometry, the proportion of cells expressing hsp72 in cytoplasm was significantly higher in allogeneic marrow transplant recipients (22 ± 15%, mean ±standard deviation (SD)) and AA patients (17 ± 21%) than in normal individuals (6 ± 3%). When PBMC were tested after heat treatment, only the proportion of hsp72+ cells of AA patients (37 ± 30%) was significantly higher than that of the normal control (17 ± 11%). Dual fluorescence analysis of the PBMC revealed that the majority of hsp72+ cells was CD3+. For 28 untreated AA patients, the proportion of hsp72+ cells in those who later responded to cyclosporine (CyA) (62 ± 24%) was higher than that in non‐responders (19 ± 13%). Immunoblotting analysis revealed predominant expression of hsp72 in T cells. These findings indicate that high inducibility of hsp72 in PBMC by heat treatment is an immunologic aberration characteristic of CyA‐responsive AA and that this simple test may be useful for identifying a subset of AA patients responsive to immunosuppressive therapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anemia, Aplastic - drug therapy</subject><subject>Anemia, Aplastic - metabolism</subject><subject>aplastic anaemia</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Child</subject><subject>Cyclosporine - therapeutic use</subject><subject>cyclosporine A</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>heat shock protein 72</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>HSP72 Heat-Shock Proteins</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunomodulators</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUGO1DAQRSMEYpqBKyAvEIJFgh0nnRiJBYyABo3EBtZWxanQ7nHsYCcw2XEErsYVOAk23QIkNqzKLr_65aqfZYTRgtFq--RQML6t85JVrGBCiIKyuqLF9Y1s8_vhZrahlDZ5LGjPsjshHChlnNbsdnaWRGgtqk32fac_7om2_aJ0p42eV-IGskeYSdg7dUUm72bUljQlebQPU1M-jjSZ0Otpjx4M6YxzPRmddXZRBsEThcaEJAOTgTBrRcACjhrIBLNGO4enBIhHo6EzSEbwV-gTr8dxsfjj67cRew0z9v8qeAyTs0F_RjI7olZlXEx4beM9_Wda72a3BjAB753iefbh1cv3F7v88t3rNxfPL3PFRUXzgXatEO2g6i4uoh8a2lecd6XgSihat0NX923DKPS8Vg0igxgoClSlEIOo-Hn28KgbN_RpwTDLUYc0Olh0S5DbqN5UlYhgewSVdyF4HOTkdRx6lYzK5IQ8yOSaTK7JZKf8Zae8jqX3Tz2WLu7kr8KjfxF4cAIgKDCDB6t0-MOJum0bHrFnR-yLNrj-d3_54u0unfhPruPA-A</recordid><startdate>199908</startdate><enddate>199908</enddate><creator>Takami, Akiyoshi</creator><creator>Nakao, Shinji</creator><creator>Tatsumi, Yasuaki</creator><creator>Wang, Hongbo</creator><creator>Weihua, Zeng</creator><creator>Yamazaki, Hirohito</creator><creator>Yasue, Shizuka</creator><creator>Shiobara, Shintaro</creator><creator>Matsuda, Tamotsu</creator><creator>Mizoguchi, Hideaki</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199908</creationdate><title>High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anaemia patients: a reliable marker of immune‐mediated aplastic anaemia responsive to cyclosporine therapy</title><author>Takami, Akiyoshi ; Nakao, Shinji ; Tatsumi, Yasuaki ; Wang, Hongbo ; Weihua, Zeng ; Yamazaki, Hirohito ; Yasue, Shizuka ; Shiobara, Shintaro ; Matsuda, Tamotsu ; Mizoguchi, Hideaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3940-f0b8998fc5b594df70d433b293c9c058fb5d8710ad35c7ee1a5c70e9ec299f943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anemia, Aplastic - drug therapy</topic><topic>Anemia, Aplastic - metabolism</topic><topic>aplastic anaemia</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Child</topic><topic>Cyclosporine - therapeutic use</topic><topic>cyclosporine A</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>heat shock protein 72</topic><topic>Heat-Shock Proteins - metabolism</topic><topic>HSP72 Heat-Shock Proteins</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunomodulators</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takami, Akiyoshi</creatorcontrib><creatorcontrib>Nakao, Shinji</creatorcontrib><creatorcontrib>Tatsumi, Yasuaki</creatorcontrib><creatorcontrib>Wang, Hongbo</creatorcontrib><creatorcontrib>Weihua, Zeng</creatorcontrib><creatorcontrib>Yamazaki, Hirohito</creatorcontrib><creatorcontrib>Yasue, Shizuka</creatorcontrib><creatorcontrib>Shiobara, Shintaro</creatorcontrib><creatorcontrib>Matsuda, Tamotsu</creatorcontrib><creatorcontrib>Mizoguchi, Hideaki</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takami, Akiyoshi</au><au>Nakao, Shinji</au><au>Tatsumi, Yasuaki</au><au>Wang, Hongbo</au><au>Weihua, Zeng</au><au>Yamazaki, Hirohito</au><au>Yasue, Shizuka</au><au>Shiobara, Shintaro</au><au>Matsuda, Tamotsu</au><au>Mizoguchi, Hideaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anaemia patients: a reliable marker of immune‐mediated aplastic anaemia responsive to cyclosporine therapy</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>1999-08</date><risdate>1999</risdate><volume>106</volume><issue>2</issue><spage>377</spage><epage>384</epage><pages>377-384</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>To better characterize immunologic aberrations in aplastic anaemia (AA), we examined peripheral blood mononuclear cells (PBMC) of 67 patients with AA and other patients with various haematological diseases for the expression of heat shock protein 72 (hsp72), which is inducible in lymphocytes by various stressors including antigenic stimulation. When freshly obtained PBMC were examined using flow cytometry, the proportion of cells expressing hsp72 in cytoplasm was significantly higher in allogeneic marrow transplant recipients (22 ± 15%, mean ±standard deviation (SD)) and AA patients (17 ± 21%) than in normal individuals (6 ± 3%). When PBMC were tested after heat treatment, only the proportion of hsp72+ cells of AA patients (37 ± 30%) was significantly higher than that of the normal control (17 ± 11%). Dual fluorescence analysis of the PBMC revealed that the majority of hsp72+ cells was CD3+. For 28 untreated AA patients, the proportion of hsp72+ cells in those who later responded to cyclosporine (CyA) (62 ± 24%) was higher than that in non‐responders (19 ± 13%). Immunoblotting analysis revealed predominant expression of hsp72 in T cells. These findings indicate that high inducibility of hsp72 in PBMC by heat treatment is an immunologic aberration characteristic of CyA‐responsive AA and that this simple test may be useful for identifying a subset of AA patients responsive to immunosuppressive therapy.</abstract><cop>Oxford, U.K. and Cambridge, USA</cop><pub>Blackwell Science Ltd</pub><pmid>10460594</pmid><doi>10.1046/j.1365-2141.1999.01540.x</doi><tpages>8</tpages></addata></record> |
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subjects | Adolescent Adult Aged Aged, 80 and over Anemia, Aplastic - drug therapy Anemia, Aplastic - metabolism aplastic anaemia Biological and medical sciences Biomarkers Child Cyclosporine - therapeutic use cyclosporine A Female Flow Cytometry heat shock protein 72 Heat-Shock Proteins - metabolism HSP72 Heat-Shock Proteins Humans Immunoblotting Immunomodulators Immunosuppressive Agents - therapeutic use Leukocytes, Mononuclear - immunology Lymphocyte Activation Male Medical sciences Middle Aged Pharmacology. Drug treatments |
title | High inducibility of heat shock protein 72 (hsp72) in peripheral blood mononuclear cells of aplastic anaemia patients: a reliable marker of immune‐mediated aplastic anaemia responsive to cyclosporine therapy |
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