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B cell reconstitution and T helper cell balance after rituximab treatment of active primary Sjögren's syndrome: A double‐blind, placebo‐controlled study

Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on...

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Published in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-04, Vol.63 (4), p.1116-1123
Main Authors: Abdulahad, W. H., Meijer, J. M., Kroese, F. G. M., Meiners, P. M., Vissink, A., Spijkervet, F. K. L., Kallenberg, C. G. M., Bootsma, H.
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container_title Arthritis & rheumatology (Hoboken, N.J.)
container_volume 63
creator Abdulahad, W. H.
Meijer, J. M.
Kroese, F. G. M.
Meiners, P. M.
Vissink, A.
Spijkervet, F. K. L.
Kallenberg, C. G. M.
Bootsma, H.
description Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4‐color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab‐treated patients were compared with those in patients receiving placebo and with those in age‐ and sex‐matched healthy controls (n = 10). Results At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27– B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class–switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow–derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.
doi_str_mv 10.1002/art.30236
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H. ; Meijer, J. M. ; Kroese, F. G. M. ; Meiners, P. M. ; Vissink, A. ; Spijkervet, F. K. L. ; Kallenberg, C. G. M. ; Bootsma, H.</creator><creatorcontrib>Abdulahad, W. H. ; Meijer, J. M. ; Kroese, F. G. M. ; Meiners, P. M. ; Vissink, A. ; Spijkervet, F. K. L. ; Kallenberg, C. G. M. ; Bootsma, H.</creatorcontrib><description>Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4‐color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab‐treated patients were compared with those in patients receiving placebo and with those in age‐ and sex‐matched healthy controls (n = 10). Results At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27– B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class–switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow–derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.</description><identifier>ISSN: 0004-3591</identifier><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 1529-0131</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.30236</identifier><identifier>PMID: 21225693</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Antibodies, Monoclonal, Murine-Derived - pharmacology ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Antirheumatic Agents - pharmacology ; Antirheumatic Agents - therapeutic use ; B-Lymphocytes - drug effects ; B-Lymphocytes - metabolism ; B-Lymphocytes - pathology ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - pathology ; Cell Count ; Diseases of the osteoarticular system ; Double-Blind Method ; Female ; Humans ; Immunoglobulin D - metabolism ; Immunoglobulin M - metabolism ; Immunomodulators ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Rituximab ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Sjogren's Syndrome - drug therapy ; Sjogren's Syndrome - metabolism ; Sjogren's Syndrome - pathology ; T-Lymphocytes, Helper-Inducer - drug effects ; T-Lymphocytes, Helper-Inducer - metabolism ; T-Lymphocytes, Helper-Inducer - pathology ; Time Factors ; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism</subject><ispartof>Arthritis &amp; rheumatology (Hoboken, N.J.), 2011-04, Vol.63 (4), p.1116-1123</ispartof><rights>Copyright © 2011 by the American College of Rheumatology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3476-7f34a2429473a6ae5c9a57855f3ffa34e05f25bf27922109e5e65e57fc26d3e73</citedby><cites>FETCH-LOGICAL-c3476-7f34a2429473a6ae5c9a57855f3ffa34e05f25bf27922109e5e65e57fc26d3e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=24134328$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21225693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abdulahad, W. H.</creatorcontrib><creatorcontrib>Meijer, J. M.</creatorcontrib><creatorcontrib>Kroese, F. G. M.</creatorcontrib><creatorcontrib>Meiners, P. M.</creatorcontrib><creatorcontrib>Vissink, A.</creatorcontrib><creatorcontrib>Spijkervet, F. K. L.</creatorcontrib><creatorcontrib>Kallenberg, C. G. M.</creatorcontrib><creatorcontrib>Bootsma, H.</creatorcontrib><title>B cell reconstitution and T helper cell balance after rituximab treatment of active primary Sjögren's syndrome: A double‐blind, placebo‐controlled study</title><title>Arthritis &amp; rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheum</addtitle><description>Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4‐color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab‐treated patients were compared with those in patients receiving placebo and with those in age‐ and sex‐matched healthy controls (n = 10). Results At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27– B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class–switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow–derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.</description><subject>Adult</subject><subject>Antibodies, Monoclonal, Murine-Derived - pharmacology</subject><subject>Antibodies, Monoclonal, Murine-Derived - therapeutic use</subject><subject>Antirheumatic Agents - pharmacology</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - pathology</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>Cell Count</subject><subject>Diseases of the osteoarticular system</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin D - metabolism</subject><subject>Immunoglobulin M - metabolism</subject><subject>Immunomodulators</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. 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Vasculitis</subject><subject>Sjogren's Syndrome - drug therapy</subject><subject>Sjogren's Syndrome - metabolism</subject><subject>Sjogren's Syndrome - pathology</subject><subject>T-Lymphocytes, Helper-Inducer - drug effects</subject><subject>T-Lymphocytes, Helper-Inducer - metabolism</subject><subject>T-Lymphocytes, Helper-Inducer - pathology</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism</subject><issn>0004-3591</issn><issn>2326-5191</issn><issn>1529-0131</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp10d1qFDEUB_AgFrtWL3wBCYgUodPmc7Lj3VrUCgVB1-shkznRWTLJNsmoe-cj-AK-hi_gm_gkpp1VQfAqJPlxzkn-CD2g5JQSws50zKecMF7fQgsqWVMRyulttCCEiIrLhh6iuyltypZxye-gQ0YZk3XDF-jbM2zAORzBBJ_ykKc8BI-17_EafwC3hTiDTjvtDWBtczmKBX4eRt3hHEHnEXzGwWJt8vAR8DaWq7jDbzc_vr-P4I8TTjvfxzDCU7zCfZg6Bz-_fO3c4PsTvHXaQBfKQZkhx-Ac9Djlqd_dQwdWuwT39-sRevfi-fr8orp8_fLV-eqyMlyoulKWC80Ea4TiutYgTaOlWkppubWaCyDSMtlZphrGKGlAQi1BKmtY3XNQ_Agdz3W3MVxNkHI7Dun62dpDmFK7lI2SUjR1kY_-kZswRV-Ga6mkikilOCnqyaxMDClFsO3-S1pK2uvI2hJZexNZsQ_3FaduhP6P_J1RAY_3QCejnY0lhyH9dYJywdmyuLPZfRoc7P7fsV29Wc-tfwEQNrEZ</recordid><startdate>201104</startdate><enddate>201104</enddate><creator>Abdulahad, W. 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Drug treatments</topic><topic>Rituximab</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Sjogren's Syndrome - drug therapy</topic><topic>Sjogren's Syndrome - metabolism</topic><topic>Sjogren's Syndrome - pathology</topic><topic>T-Lymphocytes, Helper-Inducer - drug effects</topic><topic>T-Lymphocytes, Helper-Inducer - metabolism</topic><topic>T-Lymphocytes, Helper-Inducer - pathology</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdulahad, W. H.</creatorcontrib><creatorcontrib>Meijer, J. M.</creatorcontrib><creatorcontrib>Kroese, F. G. M.</creatorcontrib><creatorcontrib>Meiners, P. M.</creatorcontrib><creatorcontrib>Vissink, A.</creatorcontrib><creatorcontrib>Spijkervet, F. K. L.</creatorcontrib><creatorcontrib>Kallenberg, C. G. 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H.</au><au>Meijer, J. M.</au><au>Kroese, F. G. M.</au><au>Meiners, P. M.</au><au>Vissink, A.</au><au>Spijkervet, F. K. L.</au><au>Kallenberg, C. G. M.</au><au>Bootsma, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>B cell reconstitution and T helper cell balance after rituximab treatment of active primary Sjögren's syndrome: A double‐blind, placebo‐controlled study</atitle><jtitle>Arthritis &amp; rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheum</addtitle><date>2011-04</date><risdate>2011</risdate><volume>63</volume><issue>4</issue><spage>1116</spage><epage>1123</epage><pages>1116-1123</pages><issn>0004-3591</issn><issn>2326-5191</issn><eissn>1529-0131</eissn><eissn>2326-5205</eissn><coden>ARHEAW</coden><abstract>Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4‐color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab‐treated patients were compared with those in patients receiving placebo and with those in age‐ and sex‐matched healthy controls (n = 10). Results At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27– B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class–switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow–derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21225693</pmid><doi>10.1002/art.30236</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Antibodies, Monoclonal, Murine-Derived - pharmacology
Antibodies, Monoclonal, Murine-Derived - therapeutic use
Antirheumatic Agents - pharmacology
Antirheumatic Agents - therapeutic use
B-Lymphocytes - drug effects
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
Biological and medical sciences
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
Cell Count
Diseases of the osteoarticular system
Double-Blind Method
Female
Humans
Immunoglobulin D - metabolism
Immunoglobulin M - metabolism
Immunomodulators
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Rituximab
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Sjogren's Syndrome - drug therapy
Sjogren's Syndrome - metabolism
Sjogren's Syndrome - pathology
T-Lymphocytes, Helper-Inducer - drug effects
T-Lymphocytes, Helper-Inducer - metabolism
T-Lymphocytes, Helper-Inducer - pathology
Time Factors
Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
title B cell reconstitution and T helper cell balance after rituximab treatment of active primary Sjögren's syndrome: A double‐blind, placebo‐controlled study
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