A C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depend...
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| creator | Michelis, Regina Tadmor, Tamar Barhoum, Masad Shehadeh, Mona Shvidel, Lev Aviv, Ariel Stemer, Galia Dally, Najib Rahimi-Levene, Naomi Yuklea, Mona Braester, Andrei |
| description | Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity. |
| doi_str_mv | 10.1371/journal.pone.0209024 |
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The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0209024</identifier><identifier>PMID: 30601845</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Biology and Life Sciences ; Blotting, Western ; Chemotherapy ; Chronic lymphocytic leukemia ; Complement ; Complement Activation - genetics ; Complement Activation - physiology ; Complement C3-C5 Convertases - metabolism ; Complement C5a - genetics ; Complement C5a - physiology ; Complement component C3 ; Complement component C4 ; Complement component C5a ; Complement Membrane Attack Complex - genetics ; Complement Membrane Attack Complex - metabolism ; Complement system ; Cytotoxicity ; Diagnosis ; Female ; Hematology ; Humans ; Immunoglobulins ; Immunotherapy ; Laboratories ; Lectins ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - blood ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemia, Lymphoid - blood ; Leukemia, Lymphoid - metabolism ; Lymphatic leukemia ; Male ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Monoclonal antibodies ; Pathogens ; Patients ; Plasma ; Research and Analysis Methods ; Structural integrity ; Toxicity</subject><ispartof>PloS one, 2019-01, Vol.14 (1), p.e0209024-e0209024</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Michelis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.</description><subject>Activation</subject><subject>Biology and Life Sciences</subject><subject>Blotting, Western</subject><subject>Chemotherapy</subject><subject>Chronic lymphocytic leukemia</subject><subject>Complement</subject><subject>Complement Activation - genetics</subject><subject>Complement Activation - physiology</subject><subject>Complement C3-C5 Convertases - metabolism</subject><subject>Complement C5a - genetics</subject><subject>Complement C5a - physiology</subject><subject>Complement component C3</subject><subject>Complement component C4</subject><subject>Complement component C5a</subject><subject>Complement Membrane Attack Complex - genetics</subject><subject>Complement 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C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity</title><author>Michelis, Regina ; Tadmor, Tamar ; Barhoum, Masad ; Shehadeh, Mona ; Shvidel, Lev ; Aviv, Ariel ; Stemer, Galia ; Dally, Najib ; Rahimi-Levene, Naomi ; Yuklea, Mona ; Braester, Andrei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b2fb4f4a811fe71cdac3371e7ee868c6506632807acc63ca69fb422e51dc2aaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>Biology and Life Sciences</topic><topic>Blotting, Western</topic><topic>Chemotherapy</topic><topic>Chronic lymphocytic leukemia</topic><topic>Complement</topic><topic>Complement Activation - genetics</topic><topic>Complement Activation - physiology</topic><topic>Complement C3-C5 Convertases - metabolism</topic><topic>Complement C5a - genetics</topic><topic>Complement C5a 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L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-01-02</date><risdate>2019</risdate><volume>14</volume><issue>1</issue><spage>e0209024</spage><epage>e0209024</epage><pages>e0209024-e0209024</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30601845</pmid><doi>10.1371/journal.pone.0209024</doi><tpages>e0209024</tpages><orcidid>https://orcid.org/0000-0002-3513-9016</orcidid><orcidid>https://orcid.org/0000-0002-3435-8612</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2162764129 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Activation Biology and Life Sciences Blotting, Western Chemotherapy Chronic lymphocytic leukemia Complement Complement Activation - genetics Complement Activation - physiology Complement C3-C5 Convertases - metabolism Complement C5a - genetics Complement C5a - physiology Complement component C3 Complement component C4 Complement component C5a Complement Membrane Attack Complex - genetics Complement Membrane Attack Complex - metabolism Complement system Cytotoxicity Diagnosis Female Hematology Humans Immunoglobulins Immunotherapy Laboratories Lectins Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - blood Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemia, Lymphoid - blood Leukemia, Lymphoid - metabolism Lymphatic leukemia Male Medicine Medicine and Health Sciences Middle Aged Monoclonal antibodies Pathogens Patients Plasma Research and Analysis Methods Structural integrity Toxicity |
| title | A C5a-Immunoglobulin complex in chronic lymphocytic leukemia patients is associated with decreased complement activity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T16%3A36%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20C5a-Immunoglobulin%20complex%20in%20chronic%20lymphocytic%20leukemia%20patients%20is%20associated%20with%20decreased%20complement%20activity&rft.jtitle=PloS%20one&rft.au=Michelis,%20Regina&rft.date=2019-01-02&rft.volume=14&rft.issue=1&rft.spage=e0209024&rft.epage=e0209024&rft.pages=e0209024-e0209024&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0209024&rft_dat=%3Cgale_plos_%3EA568068781%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2162764129&rft_id=info:pmid/30601845&rft_galeid=A568068781&rft_doaj_id=oai_doaj_org_article_743be5ed296d4aefadcc6a3d0dff0b97&rfr_iscdi=true |