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Published in: Arthritis Research & Therapy 4/2009

Open Access 01-08-2009 | Research article

Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort

Authors: Jacques-Eric Gottenberg, Corinne Miceli-Richard, Béatrice Ducot, Philippe Goupille, Bernard Combe, Xavier Mariette

Published in: Arthritis Research & Therapy | Issue 4/2009

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Abstract

Introduction

Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort.

Methods

In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients.

Results

All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA.

Conclusions

Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.
Literature
1.
go back to reference Martinez-Gamboa L, Brezinschek HP, Burmester GR, Dorner T: Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-directed therapy. Autoimmun Rev. 2006, 5: 437-442. 10.1016/j.autrev.2006.02.004.CrossRefPubMed Martinez-Gamboa L, Brezinschek HP, Burmester GR, Dorner T: Immunopathologic role of B lymphocytes in rheumatoid arthritis: rationale of B cell-directed therapy. Autoimmun Rev. 2006, 5: 437-442. 10.1016/j.autrev.2006.02.004.CrossRefPubMed
2.
go back to reference O'Neill SK, Glant TT, Finnegan A: The role of B cells in animal models of rheumatoid arthritis. Front Biosci. 2007, 12: 1722-1736. 10.2741/2184.CrossRefPubMed O'Neill SK, Glant TT, Finnegan A: The role of B cells in animal models of rheumatoid arthritis. Front Biosci. 2007, 12: 1722-1736. 10.2741/2184.CrossRefPubMed
3.
go back to reference Youinou P, Jamin C, Saraux A: B-cell: a logical target for treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2007, 25: 318-328.PubMed Youinou P, Jamin C, Saraux A: B-cell: a logical target for treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2007, 25: 318-328.PubMed
4.
go back to reference Eisenberg R, Albert D: B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006, 2: 20-27. 10.1038/ncprheum0042.CrossRefPubMed Eisenberg R, Albert D: B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006, 2: 20-27. 10.1038/ncprheum0042.CrossRefPubMed
5.
go back to reference Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ: Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2741-2749. 10.1002/art.11223.CrossRefPubMed Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ: Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003, 48: 2741-2749. 10.1002/art.11223.CrossRefPubMed
6.
go back to reference Nielen MM, van Schaardenburg D, Reesink HW, Stadt van de RJ, Horst-Bruinsma van der IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA: Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004, 50: 380-386. 10.1002/art.20018.CrossRefPubMed Nielen MM, van Schaardenburg D, Reesink HW, Stadt van de RJ, Horst-Bruinsma van der IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA: Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004, 50: 380-386. 10.1002/art.20018.CrossRefPubMed
7.
go back to reference Talal N, Grey HM, Zvaifler N, Michalski JP, Daniels TE: Elevated salivary and synovial fluid beta2-microglobulin in Sjogren's syndrome and rheumatoid arthritis. Science. 1975, 187: 1196-1198. 10.1126/science.46621.CrossRefPubMed Talal N, Grey HM, Zvaifler N, Michalski JP, Daniels TE: Elevated salivary and synovial fluid beta2-microglobulin in Sjogren's syndrome and rheumatoid arthritis. Science. 1975, 187: 1196-1198. 10.1126/science.46621.CrossRefPubMed
8.
go back to reference Aho K, Heliovaara M, Knekt P, Reunanen A, Aromaa A, Leino A, Kurki P, Heikkilä R, Palosuo T: Serum immunoglobulins and the risk of rheumatoid arthritis. Ann Rheum Dis. 1997, 56: 351-356. 10.1136/ard.56.6.351.PubMedCentralCrossRefPubMed Aho K, Heliovaara M, Knekt P, Reunanen A, Aromaa A, Leino A, Kurki P, Heikkilä R, Palosuo T: Serum immunoglobulins and the risk of rheumatoid arthritis. Ann Rheum Dis. 1997, 56: 351-356. 10.1136/ard.56.6.351.PubMedCentralCrossRefPubMed
9.
go back to reference Gottenberg JE, Aucouturier F, Goetz J, Sordet C, Jahn I, Busson M, Cayuela JM, Sibili J, Mariette X: Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren's syndrome. Ann Rheum Dis. 2007, 66: 23-27. 10.1136/ard.2006.052159.PubMedCentralCrossRefPubMed Gottenberg JE, Aucouturier F, Goetz J, Sordet C, Jahn I, Busson M, Cayuela JM, Sibili J, Mariette X: Serum immunoglobulin free light chain assessment in rheumatoid arthritis and primary Sjogren's syndrome. Ann Rheum Dis. 2007, 66: 23-27. 10.1136/ard.2006.052159.PubMedCentralCrossRefPubMed
10.
go back to reference Mackay F, Schneider P, Rennert P, Browning J: BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003, 21: 231-264. 10.1146/annurev.immunol.21.120601.141152.CrossRefPubMed Mackay F, Schneider P, Rennert P, Browning J: BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003, 21: 231-264. 10.1146/annurev.immunol.21.120601.141152.CrossRefPubMed
11.
go back to reference Combe B, Benessiano J, Berenbaum F, Cantagrel A, Daures JP, Dougados M, Fardellone P, Fautrel B, Flipo RM, Goupolle P, Guillemin F, Le Loet X, Logeart I, Mariette X, Meyer O, Ravaud P, Rincheval N, Saraux A, Schaeverbeke T, Sibilia J: The ESPOIR cohort: a ten-year follow-up of early arthritis in France: methodology and baseline characteristics of the 813 included patients. Joint Bone Spine. 2007, 74: 440-445. 10.1016/j.jbspin.2007.06.001.CrossRefPubMed Combe B, Benessiano J, Berenbaum F, Cantagrel A, Daures JP, Dougados M, Fardellone P, Fautrel B, Flipo RM, Goupolle P, Guillemin F, Le Loet X, Logeart I, Mariette X, Meyer O, Ravaud P, Rincheval N, Saraux A, Schaeverbeke T, Sibilia J: The ESPOIR cohort: a ten-year follow-up of early arthritis in France: methodology and baseline characteristics of the 813 included patients. Joint Bone Spine. 2007, 74: 440-445. 10.1016/j.jbspin.2007.06.001.CrossRefPubMed
12.
go back to reference Emmerich F, Bal G, Barakat A, Milz J, Muhle C, Martinez-Gamboa L, Dörner T, Salama A: High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2007, 136: 309-314. 10.1111/j.1365-2141.2006.06431.x.CrossRefPubMed Emmerich F, Bal G, Barakat A, Milz J, Muhle C, Martinez-Gamboa L, Dörner T, Salama A: High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2007, 136: 309-314. 10.1111/j.1365-2141.2006.06431.x.CrossRefPubMed
13.
go back to reference Gottenberg JE, Sellam J, Ittah M, Lavie F, Proust A, Zouali H, Sordet C, Sibilia J, Kimberly RP, Mariette X, Miceli-Richard C: No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjogren's syndrome. Arthritis Res Ther. 2006, 8: R30-10.1186/ar1884.PubMedCentralCrossRefPubMed Gottenberg JE, Sellam J, Ittah M, Lavie F, Proust A, Zouali H, Sordet C, Sibilia J, Kimberly RP, Mariette X, Miceli-Richard C: No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjogren's syndrome. Arthritis Res Ther. 2006, 8: R30-10.1186/ar1884.PubMedCentralCrossRefPubMed
14.
go back to reference Novak AJ, Grote DM, Ziesmer SC, Kline MP, Manske MK, Slager S, Witzig TE, Shanafelt T, Call TG, Kay NE, Jelinek DF, Cerhan JR, Gross JA, Harder B, Dillon SR, Ansell SM: Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders. J Clin Oncol. 2006, 24: 983-987. 10.1200/JCO.2005.02.7938.CrossRefPubMed Novak AJ, Grote DM, Ziesmer SC, Kline MP, Manske MK, Slager S, Witzig TE, Shanafelt T, Call TG, Kay NE, Jelinek DF, Cerhan JR, Gross JA, Harder B, Dillon SR, Ansell SM: Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders. J Clin Oncol. 2006, 24: 983-987. 10.1200/JCO.2005.02.7938.CrossRefPubMed
15.
go back to reference Devauchelle-Pensec V, Josseaume T, Samjee I, Dougados M, Combe B, Saraux A: Ability of oblique foot radiographs to detect erosions in early arthritis: results in the ESPOIR cohort. Arthritis Rheum. 2008, 59: 1729-1734. 10.1002/art.24310.CrossRefPubMed Devauchelle-Pensec V, Josseaume T, Samjee I, Dougados M, Combe B, Saraux A: Ability of oblique foot radiographs to detect erosions in early arthritis: results in the ESPOIR cohort. Arthritis Rheum. 2008, 59: 1729-1734. 10.1002/art.24310.CrossRefPubMed
16.
go back to reference Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X: Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007, 66: 700-703. 10.1136/ard.2006.060772.PubMedCentralCrossRefPubMed Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X: Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007, 66: 700-703. 10.1136/ard.2006.060772.PubMedCentralCrossRefPubMed
17.
go back to reference Vallerskog T, Heimburger M, Gunnarsson I, Zhou W, Wahren-Herlenius M, Trollmo C, Malström V: Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006, 8: R167-10.1186/ar2076.PubMedCentralCrossRefPubMed Vallerskog T, Heimburger M, Gunnarsson I, Zhou W, Wahren-Herlenius M, Trollmo C, Malström V: Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther. 2006, 8: R167-10.1186/ar2076.PubMedCentralCrossRefPubMed
18.
go back to reference Saraux A, Berthelot JM, Chales G, Le Henaff C, Thorel JB, Hoang S, Valls I, Devauchelle V, Martin A, Baron D, Pennec Y, Botton E, Mary JY, Le Goff P, Youinou P: Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum. 2001, 44: 2485-2491. 10.1002/1529-0131(200111)44:11<2485::AID-ART428>3.0.CO;2-S.CrossRefPubMed Saraux A, Berthelot JM, Chales G, Le Henaff C, Thorel JB, Hoang S, Valls I, Devauchelle V, Martin A, Baron D, Pennec Y, Botton E, Mary JY, Le Goff P, Youinou P: Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum. 2001, 44: 2485-2491. 10.1002/1529-0131(200111)44:11<2485::AID-ART428>3.0.CO;2-S.CrossRefPubMed
19.
go back to reference Helm-van Mil Van der AHM, le Cessie S, van Dongen H, Breedveld FC, Toes REM, Huizinga TWJ: A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis. Arthritis Rheum. 2007, 56: 433-440. 10.1002/art.22380.CrossRefPubMed Helm-van Mil Van der AHM, le Cessie S, van Dongen H, Breedveld FC, Toes REM, Huizinga TWJ: A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis. Arthritis Rheum. 2007, 56: 433-440. 10.1002/art.22380.CrossRefPubMed
20.
go back to reference Symmons DP, Silman AJ: Aspects of early arthritis. What determines the evolution of early undifferentiated arthritis and rheumatoid arthritis? An update from the Norfolk Arthritis Register. Arthritis Res Ther. 2006, 8: 214-10.1186/ar1979.PubMedCentralCrossRefPubMed Symmons DP, Silman AJ: Aspects of early arthritis. What determines the evolution of early undifferentiated arthritis and rheumatoid arthritis? An update from the Norfolk Arthritis Register. Arthritis Res Ther. 2006, 8: 214-10.1186/ar1979.PubMedCentralCrossRefPubMed
21.
go back to reference Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, Rantapää-Dahlqvist S: Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis. 2006, 65: 453-458. 10.1136/ard.2005.041376.PubMedCentralCrossRefPubMed Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, Rantapää-Dahlqvist S: Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis. 2006, 65: 453-458. 10.1136/ard.2005.041376.PubMedCentralCrossRefPubMed
22.
go back to reference Forslind K, Ahlmén M, Eberhardt K, Hafström I, Svensson B, BARFOT Study Group: Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004, 63: 1090-1095. 10.1136/ard.2003.014233.PubMedCentralCrossRefPubMed Forslind K, Ahlmén M, Eberhardt K, Hafström I, Svensson B, BARFOT Study Group: Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004, 63: 1090-1095. 10.1136/ard.2003.014233.PubMedCentralCrossRefPubMed
23.
go back to reference Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA: Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002, 48: 1437-1444.PubMed Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA: Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem. 2002, 48: 1437-1444.PubMed
24.
go back to reference Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K: Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis. Genes Immun. 2001, 2: 276-279. 10.1038/sj.gene.6363770.CrossRefPubMed Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K: Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis. Genes Immun. 2001, 2: 276-279. 10.1038/sj.gene.6363770.CrossRefPubMed
25.
go back to reference Cheema GS, Roschke V, Hilbert DM, Stohl W: Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001, 44: 1313-1319. 10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S.CrossRefPubMed Cheema GS, Roschke V, Hilbert DM, Stohl W: Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001, 44: 1313-1319. 10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S.CrossRefPubMed
26.
go back to reference Collins CE, Gavin AL, Migone TS, Hilbert DM, Nemazee D, Stohl W: B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels. Arthritis Res Ther. 2006, 8: R6-10.1186/ar1855.PubMedCentralCrossRefPubMed Collins CE, Gavin AL, Migone TS, Hilbert DM, Nemazee D, Stohl W: B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels. Arthritis Res Ther. 2006, 8: R6-10.1186/ar1855.PubMedCentralCrossRefPubMed
27.
go back to reference Tan SM, Xu D, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone TS, Hilbert DM, Stohl W: Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003, 48: 982-992. 10.1002/art.10860.CrossRefPubMed Tan SM, Xu D, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, Migone TS, Hilbert DM, Stohl W: Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum. 2003, 48: 982-992. 10.1002/art.10860.CrossRefPubMed
28.
go back to reference Bosello S, Youinou P, Daridon C, Tolusso B, Bendaoud B, Pietrapertosa D, Morelli A, Ferraccioli G: Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008, 35: 1256-1264.PubMed Bosello S, Youinou P, Daridon C, Tolusso B, Bendaoud B, Pietrapertosa D, Morelli A, Ferraccioli G: Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008, 35: 1256-1264.PubMed
29.
go back to reference Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M: Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005, 7: R784-795. 10.1186/ar1733.PubMedCentralCrossRefPubMed Raza K, Falciani F, Curnow SJ, Ross EJ, Lee CY, Akbar AN, Lord JM, Gordon C, Buckley CD, Salmon M: Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005, 7: R784-795. 10.1186/ar1733.PubMedCentralCrossRefPubMed
30.
go back to reference Xu W, He B, Chiu A, Chadburn A, Shan M, Buldys M, Ding A, Knowles DM, Santini PA, Cerutti A: Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat Immunol. 2007, 8: 294-303. 10.1038/ni1434.CrossRefPubMed Xu W, He B, Chiu A, Chadburn A, Shan M, Buldys M, Ding A, Knowles DM, Santini PA, Cerutti A: Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat Immunol. 2007, 8: 294-303. 10.1038/ni1434.CrossRefPubMed
31.
go back to reference Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA: Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006, 24: 99-146. 10.1146/annurev.immunol.24.021605.090737.CrossRefPubMed Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA: Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006, 24: 99-146. 10.1146/annurev.immunol.24.021605.090737.CrossRefPubMed
32.
go back to reference Seyler TM, Park YW, Takemura S, Bram RJ, Kurtin PJ, Goronzy JJ, Weyand CM: BLyS and APRIL in rheumatoid arthritis. J Clin Invest. 2005, 115: 3083-3092. 10.1172/JCI25265.PubMedCentralCrossRefPubMed Seyler TM, Park YW, Takemura S, Bram RJ, Kurtin PJ, Goronzy JJ, Weyand CM: BLyS and APRIL in rheumatoid arthritis. J Clin Invest. 2005, 115: 3083-3092. 10.1172/JCI25265.PubMedCentralCrossRefPubMed
Metadata
Title
Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort
Authors
Jacques-Eric Gottenberg
Corinne Miceli-Richard
Béatrice Ducot
Philippe Goupille
Bernard Combe
Xavier Mariette
Publication date
01-08-2009
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2009
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2773

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