Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias
Summary T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immu...
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| Veröffentlicht in: | British journal of haematology 2007-01, Vol.136 (2), p.237-248 |
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| creator | Nearman, Zachary P. Wlodarski, Marcin Jankowska, Anna M. Howe, Evan Narvaez, Yadira Ball, Edward Maciejewski, Jaroslaw P. |
| description | Summary
T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune‐mediated bone marrow failure and autoimmune conditions, may promote T‐LGL evolution and/or development of cytopenias. The association of T‐LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer‐cell immunoglobulin‐like receptor (KIR) genotype, KIR/KIR‐L mismatch, CTLA‐4 (+49 A/G),CD16−158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF‐α (−308G/A), TGF‐β1 (codons 10 C/T, 25 G/C), IL‐10 (−1082 G/A), IL‐6 (−174 C/G), and IFN‐γ(+874 T/A). A statistically significant increase in A/A genotype for TNF‐α−308, IL‐10–1082, andCTLA‐4 +49 was observed in T‐LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR‐L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA‐A3/11 and HLA‐C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T‐LGL requires future analysis. |
| doi_str_mv | 10.1111/j.1365-2141.2006.06429.x |
| format | Article |
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T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune‐mediated bone marrow failure and autoimmune conditions, may promote T‐LGL evolution and/or development of cytopenias. The association of T‐LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer‐cell immunoglobulin‐like receptor (KIR) genotype, KIR/KIR‐L mismatch, CTLA‐4 (+49 A/G),CD16−158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF‐α (−308G/A), TGF‐β1 (codons 10 C/T, 25 G/C), IL‐10 (−1082 G/A), IL‐6 (−174 C/G), and IFN‐γ(+874 T/A). A statistically significant increase in A/A genotype for TNF‐α−308, IL‐10–1082, andCTLA‐4 +49 was observed in T‐LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR‐L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA‐A3/11 and HLA‐C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T‐LGL requires future analysis.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2006.06429.x</identifier><identifier>PMID: 17156396</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Antigens, CD - genetics ; Antigens, Differentiation - genetics ; Biological and medical sciences ; Case-Control Studies ; Chi-Square Distribution ; CTLA-4 Antigen ; cytokines ; Cytokines - genetics ; Cytotoxicity, Immunologic ; Flow Cytometry ; Gene Frequency ; Genotype ; Hematologic and hematopoietic diseases ; Histocompatibility Antigens Class I ; human leucocyte antigen ; Humans ; Immunogenetics ; Immunoglobulin Variable Region - genetics ; Immunophenotyping ; leukaemia ; Leukemia, T-Cell - genetics ; Leukemia, T-Cell - immunology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Leukocyte Common Antigens - genetics ; Ligands ; Medical sciences ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, Cytokine - genetics ; Receptors, IgG - genetics ; Receptors, Immunologic ; Receptors, KIR ; Receptors, KIR3DL2 ; single‐nucleotide polymorphisms ; Statistics, Nonparametric ; T-Lymphocytes, Cytotoxic - immunology ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>British journal of haematology, 2007-01, Vol.136 (2), p.237-248</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3979-59016be0ada3ca7454d00fe93815299233b6c7846c027d5e5ad03281155347c23</citedby><cites>FETCH-LOGICAL-c3979-59016be0ada3ca7454d00fe93815299233b6c7846c027d5e5ad03281155347c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2141.2006.06429.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2141.2006.06429.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,4024,27923,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18488691$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17156396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nearman, Zachary P.</creatorcontrib><creatorcontrib>Wlodarski, Marcin</creatorcontrib><creatorcontrib>Jankowska, Anna M.</creatorcontrib><creatorcontrib>Howe, Evan</creatorcontrib><creatorcontrib>Narvaez, Yadira</creatorcontrib><creatorcontrib>Ball, Edward</creatorcontrib><creatorcontrib>Maciejewski, Jaroslaw P.</creatorcontrib><title>Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune‐mediated bone marrow failure and autoimmune conditions, may promote T‐LGL evolution and/or development of cytopenias. The association of T‐LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer‐cell immunoglobulin‐like receptor (KIR) genotype, KIR/KIR‐L mismatch, CTLA‐4 (+49 A/G),CD16−158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF‐α (−308G/A), TGF‐β1 (codons 10 C/T, 25 G/C), IL‐10 (−1082 G/A), IL‐6 (−174 C/G), and IFN‐γ(+874 T/A). A statistically significant increase in A/A genotype for TNF‐α−308, IL‐10–1082, andCTLA‐4 +49 was observed in T‐LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR‐L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA‐A3/11 and HLA‐C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T‐LGL requires future analysis.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, Differentiation - genetics</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Chi-Square Distribution</subject><subject>CTLA-4 Antigen</subject><subject>cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytotoxicity, Immunologic</subject><subject>Flow Cytometry</subject><subject>Gene Frequency</subject><subject>Genotype</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Histocompatibility Antigens Class I</subject><subject>human leucocyte antigen</subject><subject>Humans</subject><subject>Immunogenetics</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunophenotyping</subject><subject>leukaemia</subject><subject>Leukemia, T-Cell - genetics</subject><subject>Leukemia, T-Cell - immunology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Leukocyte Common Antigens - genetics</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, Cytokine - genetics</subject><subject>Receptors, IgG - genetics</subject><subject>Receptors, Immunologic</subject><subject>Receptors, KIR</subject><subject>Receptors, KIR3DL2</subject><subject>single‐nucleotide polymorphisms</subject><subject>Statistics, Nonparametric</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1u1DAQgC0EokvhFZAvcEvwf-wDB6iAFlXiUs6W15lsvTj2EielufEIPCNPQsKu6JW5zEjzzY8-hDAlNV3izb6mXMmKUUFrRoiqiRLM1PeP0OZf4zHaEEKaihKhz9CzUvaEUE4kfYrOaEOl4kZt0HzV91PKO0gwBo8758c8FNzCCEMfUkg7PN4ChrscpzHkhHOHb37__OUhRhzdsAO8G1yalhLHuT_cZj-PgCNM3xz0wWGXWuxKyT64EVq8dPMBUnDlOXrSuVjgxSmfo68fP9xcXFbXXz5dXby7rjw3jamkIVRtgbjWce8aIUVLSAeGayqZMYzzrfKNFsoT1rQSpGsJZ5pSKbloPOPn6PVx72HI3ycoo-1DWd93CfJUrNKGU2bEAuoj6IdcygCdPQyhd8NsKbGrdru3q1272rWrdvtXu71fRl-ebkzbHtqHwZPnBXh1AlzxLnaLMh_KA6eF1srQhXt75H6ECPN_P2Dff75cK_4HVVKgNg</recordid><startdate>200701</startdate><enddate>200701</enddate><creator>Nearman, Zachary P.</creator><creator>Wlodarski, Marcin</creator><creator>Jankowska, Anna M.</creator><creator>Howe, Evan</creator><creator>Narvaez, Yadira</creator><creator>Ball, Edward</creator><creator>Maciejewski, Jaroslaw P.</creator><general>Blackwell Publishing 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>200701</creationdate><title>Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias</title><author>Nearman, Zachary P. ; Wlodarski, Marcin ; Jankowska, Anna M. ; Howe, Evan ; Narvaez, Yadira ; Ball, Edward ; Maciejewski, Jaroslaw P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3979-59016be0ada3ca7454d00fe93815299233b6c7846c027d5e5ad03281155347c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, Differentiation - genetics</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>Chi-Square Distribution</topic><topic>CTLA-4 Antigen</topic><topic>cytokines</topic><topic>Cytokines - genetics</topic><topic>Cytotoxicity, Immunologic</topic><topic>Flow Cytometry</topic><topic>Gene Frequency</topic><topic>Genotype</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Histocompatibility Antigens Class I</topic><topic>human leucocyte antigen</topic><topic>Humans</topic><topic>Immunogenetics</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunophenotyping</topic><topic>leukaemia</topic><topic>Leukemia, T-Cell - genetics</topic><topic>Leukemia, T-Cell - immunology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Leukocyte Common Antigens - genetics</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, Cytokine - genetics</topic><topic>Receptors, IgG - genetics</topic><topic>Receptors, Immunologic</topic><topic>Receptors, KIR</topic><topic>Receptors, KIR3DL2</topic><topic>single‐nucleotide polymorphisms</topic><topic>Statistics, Nonparametric</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nearman, Zachary P.</creatorcontrib><creatorcontrib>Wlodarski, Marcin</creatorcontrib><creatorcontrib>Jankowska, Anna M.</creatorcontrib><creatorcontrib>Howe, Evan</creatorcontrib><creatorcontrib>Narvaez, Yadira</creatorcontrib><creatorcontrib>Ball, Edward</creatorcontrib><creatorcontrib>Maciejewski, Jaroslaw P.</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>Nearman, Zachary P.</au><au>Wlodarski, Marcin</au><au>Jankowska, Anna M.</au><au>Howe, Evan</au><au>Narvaez, Yadira</au><au>Ball, Edward</au><au>Maciejewski, Jaroslaw P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2007-01</date><risdate>2007</risdate><volume>136</volume><issue>2</issue><spage>237</spage><epage>248</epage><pages>237-248</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune‐mediated bone marrow failure and autoimmune conditions, may promote T‐LGL evolution and/or development of cytopenias. The association of T‐LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer‐cell immunoglobulin‐like receptor (KIR) genotype, KIR/KIR‐L mismatch, CTLA‐4 (+49 A/G),CD16−158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF‐α (−308G/A), TGF‐β1 (codons 10 C/T, 25 G/C), IL‐10 (−1082 G/A), IL‐6 (−174 C/G), and IFN‐γ(+874 T/A). A statistically significant increase in A/A genotype for TNF‐α−308, IL‐10–1082, andCTLA‐4 +49 was observed in T‐LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR‐L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA‐A3/11 and HLA‐C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T‐LGL requires future analysis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17156396</pmid><doi>10.1111/j.1365-2141.2006.06429.x</doi><tpages>12</tpages></addata></record> |
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| subjects | Adult Aged Antigens, CD - genetics Antigens, Differentiation - genetics Biological and medical sciences Case-Control Studies Chi-Square Distribution CTLA-4 Antigen cytokines Cytokines - genetics Cytotoxicity, Immunologic Flow Cytometry Gene Frequency Genotype Hematologic and hematopoietic diseases Histocompatibility Antigens Class I human leucocyte antigen Humans Immunogenetics Immunoglobulin Variable Region - genetics Immunophenotyping leukaemia Leukemia, T-Cell - genetics Leukemia, T-Cell - immunology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Leukocyte Common Antigens - genetics Ligands Medical sciences Middle Aged Polymorphism, Single Nucleotide Receptors, Cytokine - genetics Receptors, IgG - genetics Receptors, Immunologic Receptors, KIR Receptors, KIR3DL2 single‐nucleotide polymorphisms Statistics, Nonparametric T-Lymphocytes, Cytotoxic - immunology Tumor Necrosis Factor-alpha - genetics |
| title | Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias |
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