Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 6/2012

01-12-2012 | Review

Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective

Authors: Serena Bugatti, Antonio Manzo, Roberto Caporali, Carlomaurizio Montecucco

Published in: Arthritis Research & Therapy | Issue 6/2012

Login to get access

Abstract

The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease.
Appendix
Available only for authorised users
Literature
1.
2.
Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L: Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol. 2008, 26: 651-675. 10.1146/annurev.immunol.26.021607.090244.CrossRefPubMed
3.
van de Sande MG, de Hair MJ, van der Leij C, Klarenbeek PL, Bos WH, Smith MD, Maas M, de Vries N, van Schaardenburg D, Dijkmans BA, Gerlag DM, Tak PP: Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis. 2011, 70: 772-777. 10.1136/ard.2010.139527.CrossRefPubMed
4.
Manzo A, Bombardieri M, Humby F, Pitzalis C: Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation to autoimmunity and tissue damage/remodeling. Immunol Rev. 2010, 233: 267-285. 10.1111/j.0105-2896.2009.00861.x.CrossRefPubMed
5.
Manzo A, Caporali R, Vitolo B, Alessi S, Benaglio F, Todoerti M, Bugatti S, Calliada F, Montecucco C: Subclinical remodelling of draining lymph node structure in early and established rheumatoid arthritis assessed by power Doppler ultrasonography. Rheumatology. 2011, 50: 1395-1400. 10.1093/rheumatology/ker076.CrossRefPubMed
6.
Schett G, Firestein GS: Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis. Ann Rheum Dis. 2010, 69: 787-789. 10.1136/ard.2009.121657.CrossRefPubMed
7.
Samuels J, Ng YS, Coupillaud C, Paget D, Meffre E: Impaired early B cell tolerance in patients with rheumatoid arthritis. J Exp Med. 2005, 201: 1659-1667. 10.1084/jem.20042321.PubMedCentralCrossRefPubMed
8.
9.
McQueen FM: A vital clue to deciphering bone pathology: MRI bone oedema in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 2007, 66: 1549-1552. 10.1136/ard.2007.082875.PubMedCentralCrossRefPubMed
10.
Schett G: Bone marrow edema. Ann N Y Acad Sci. 2009, 1154: 35-40. 10.1111/j.1749-6632.2009.04383.x.CrossRefPubMed
11.
Woodland DL, Blackman MA: Immunity: it's in our bones. Immunity. 2005, 22: 143-144. 10.1016/j.immuni.2005.02.002.CrossRefPubMed
12.
Tomita T, Kashiwagi N, Shimaoka Y, Ikawa T, Tanabe M, Nakagawa S, Kawamura S, Denno K, Owaki H, Ochi T: Phenotypic characteristics of bone marrow cells in patients with rheumatoid arthritis. J Rheumatol. 1994, 21: 1608-1614.PubMed
13.
Tomita T, Shimaoka Y, Kashiwagi N, Hashimoto H, Kawamura S, Lee SB, Nakagawa S, Shiho O, Hayashida K, Ochi T: Enhanced expression of CD14 antigen on myeloid lineage cells derived from the bone marrow of patients with severe rheumatoid arthritis. J Rheumatol. 1997, 24: 465-469.PubMed
14.
Hirohata S, Yanagida T, Itoh K, Nakamura H, Yoshino S, Tomita T, Ochi T: Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients. Arthritis Rheum. 1996, 39: 836-843. 10.1002/art.1780390517.CrossRefPubMed
15.
Tanabe M, Ochi T, Tomita T, Suzuki R, Sakata T, Shimaoka Y, Nakagawa S, Ono K: Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis. J Rheumatol. 1994, 21: 830-835.PubMed
16.
Lee HM, Sugino H, Aoki C, Shimaoka Y, Suzuki R, Ochi K, Ochi T, Nishimoto N: Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis. Arthritis Res Ther. 2011, 13: R89-10.1186/ar3364.PubMedCentralCrossRefPubMed
17.
Hayashida K, Ochi T, Fujimoto M, Owaki H, Shimaoka Y, Ono K, Matsumoto K: Bone marrow changes in adjuvant-induced and collagen-induced arthritis. Interleukin-1 and interleukin-6 activity and abnormal myelopoiesis. Arthritis Rheum. 1992, 35: 241-245. 10.1002/art.1780350219.CrossRefPubMed
18.
Proulx ST, Kwok E, You Z, Papuga MO, Beck CA, Shealy DJ, Calvi LM, Ritchlin CT, Awad HA, Boyce BF, Xing L, Schwarz EM: Elucidating bone marrow edema and myelopoiesis in murine arthritis using contrast-enhanced magnetic resonance imaging. Arthritis Rheum. 2008, 58: 2019-2029. 10.1002/art.23546.PubMedCentralCrossRefPubMed
19.
Duthie JJ, Gardner DL, Richmond J, Roy LM: Nature of anaemia in rheumatoid arthritis. III. Changes in the bone marrow and their relation to other features of the disease. Ann Rheum Dis. 1956, 15: 217-226. 10.1136/ard.15.3.217.PubMedCentralCrossRefPubMed
20.
Otten HG, Daha MR, Dolhain RJ, de Rooy HH, Breedveld FC: Rheumatoid factor production by mononuclear cells derived from different sites of patients with rheumatoid arthritis. Clin Exp Immunol. 1993, 94: 236-240.PubMedCentralCrossRefPubMed
21.
Reparon-Schuijt CC, van Esch WJ, van Kooten C, Schellekens GA, de Jong BA, van Venrooij WJ, Breedveld FC, Verweij CL: Secretion of anti-citrullinecontaining peptide antibody by B lymphocytes in rheumatoid arthritis. Arthritis Rheum. 2001, 44: 41-47. 10.1002/1529-0131(200101)44:1<41::AID-ANR6>3.0.CO;2-0.CrossRefPubMed
22.
Doita M, Maeda S, Kawai K, Hirohata K, Sugiyama T: Analysis of lymphocyte subsets of bone marrow in patients with rheumatoid arthritis by two colour immunofluorescence and flow cytometry. Ann Rheum Dis. 1990, 49: 168-171. 10.1136/ard.49.3.168.PubMedCentralCrossRefPubMed
23.
Kuca-Warnawin E, Burakowski T, Kurowska W, Prochorec-Sobieszek M, Radzikowska A, Chorazy-Massalska M, Maldyk P, Kontny E, Maslinski W: Elevated number of recently activated T cells in bone marrow of patients with rheumatoid arthritis: a role for interleukin 15?. Ann Rheum Dis. 2011, 70: 227-233. 10.1136/ard.2009.124966.CrossRefPubMed
24.
Engels K, Oeschger S, Hansmann ML, Hillebrand M, Kriener S: Bone marrow trephines containing lymphoid aggregates from patients with rheumatoid and other autoimmune disorders frequently show clonal B-cell infiltrates. Hum Pathol. 2007, 38: 1402-1411. 10.1016/j.humpath.2007.02.009.CrossRefPubMed
25.
Leandro MJ, Cooper N, Cambridge G, Ehrenstein MR, Edwards JC: Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy. Rheumatology. 2007, 46: 29-36. 10.1093/rheumatology/kel148.CrossRefPubMed
26.
Teng YK, Levarht EW, Hashemi M, Bajema IM, Toes RE, Huizinga TW, van Laar JM: Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment. Arthritis Rheum. 2007, 56: 3909-3918. 10.1002/art.22967.CrossRefPubMed
27.
Rehnberg M, Amu S, Tarkowski A, Bokarewa MI, Brisslert M: Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis. Arthritis Res Ther. 2009, 11: R123-10.1186/ar2789.PubMedCentralCrossRefPubMed
28.
Nakou M, Katsikas G, Sidiropoulos P, Bertsias G, Papadimitraki E, Raptopoulou A, Koutala H, Papadaki HA, Kritikos H, Boumpas DT: Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res Ther. 2009, 11: R131-10.1186/ar2798.PubMedCentralCrossRefPubMed
29.
Barrie HJ: Histologic changes in rheumatoid disease of the metacarpal and metatarsal heads as seen in surgical material. J Rheumatol. 1981, 8: 246-257.PubMed
30.
Wyllie JC: Histopathology of the subchondral bone lesion in rheumatoid arthritis. J Rheumatol Suppl. 1983, 11: 26-28.PubMed
31.
Bromley M, Bertfield H, Evanson JM, Woolley DE: Bidirectional erosion of cartilage in the rheumatoid knee joint. Ann Rheum Dis. 1985, 44: 676-681. 10.1136/ard.44.10.676.PubMedCentralCrossRefPubMed
32.
Watson WC, Tooms RE, Carnesale PG, Dutkowsky JP: A case of germinal center formation by CD45RO T and CD20 B lymphocytes in rheumatoid arthritic subchondral bone: proposal for a two-compartment model of immune-mediated disease with implications for immunotherapeutic strategies. Clin Immunol Immunopathol. 1994, 73: 27-37. 10.1006/clin.1994.1166.CrossRefPubMed
33.
O'Connell JX, Nielsen GP, Rosenberg AE: Subchondral acute inflammation in severe arthritis: a sterile osteomyelitis?. Am J Surg Pathol. 1999, 23: 192-197. 10.1097/00000478-199902000-00008.CrossRefPubMed
34.
Scirè CA, Epis O, Codullo V, Humby F, Morbini P, Manzo A, Caporali R, Pitzalis C, Montecucco C: Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure. Arthritis Res Ther. 2007, 9: R101-10.1186/ar2302.PubMedCentralCrossRefPubMed
35.
Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, Dorotka R, Wanivenhaus AH, Kainberger F, Trattnig S, Axmann R, Tsuji W, Hermann S, Smolen J, Schett G: Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum. 2007, 56: 1118-1124. 10.1002/art.22496.CrossRefPubMed
36.
McQueen FM, Gao A, Ostergaard M, King A, Shalley G, Robinson E, Doyle A, Clark B, Dalbeth N: High-grade MRI bone oedema is common within the surgical field in rheumatoid arthritis patients undergoing joint replacement and is associated with osteitis in subchondral bone. Ann Rheum Dis. 2007, 66: 1581-1587. 10.1136/ard.2007.070326.PubMedCentralCrossRefPubMed
37.
Dalbeth N, Smith T, Gray S, Doyle A, Antill P, Lobo M, Robinson E, King A, Cornish J, Shalley G, Gao A, McQueen FM: Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease. Ann Rheum Dis. 2009, 68: 279-282. 10.1136/ard.2008.096024.CrossRefPubMed
38.
Bugatti S, Caporali R, Manzo A, Vitolo B, Pitzalis C, Montecucco C: Involvement of subchondral bone marrow in rheumatoid arthritis: lymphoid neogenesis and in situ relationship to subchondral bone marrow osteoclast recruitment. Arthritis Rheum. 2005, 52: 3448-3459. 10.1002/art.21377.CrossRefPubMed
39.
Jimenez-Boj E, Redlich K, Türk B, Hanslik-Schnabel B, Wanivenhaus A, Chott A, Smolen JS, Schett G: Interaction between synovial inflammatory tissue and bone marrow in rheumatoid arthritis. J Immunol. 2005, 175: 2579-2588.CrossRefPubMed
40.
Bollow M, Fischer T, Reisshauer H, Backhaus M, Sieper J, Hamm B, Braun J, Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis-cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis. 2000, 59: 135-140. 10.1136/ard.59.2.135.PubMedCentralCrossRefPubMed
41.
Appel H, Loddenkemper C, Grozdanovic Z, Ebhardt H, Dreimann M, Hempfing A, Stein H, Metz-Stavenhagen P, Rudwaleit M, Sieper J: Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis. Arthritis Res Ther. 2006, 8: R143-10.1186/ar2035.PubMedCentralCrossRefPubMed
42.
Appel H, Kuhne M, Spiekermann S, Ebhardt H, Grozdanovic Z, Köhler D, Dreimann M, Hempfing A, Rudwaleit M, Stein H, Metz-Stavenhagen P, Sieper J, Loddenkemper C: Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthritis Rheum. 2006, 54: 2845-2851. 10.1002/art.22060.CrossRefPubMed
43.
Appel H, Kuhne M, Spiekermann S, Köhler D, Zacher J, Stein H, Sieper J, Loddenkemper C: Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum. 2006, 54: 1805-1813. 10.1002/art.21907.CrossRefPubMed
44.
Baeten D, Kruithof E, Breban M, Tak PP: Spondylarthritis in the absence of B lymphocytes. Arthritis Rheum. 2008, 58: 730-733. 10.1002/art.23266.CrossRefPubMed
45.
Zanetti M, Bruder E, Romero J, Hodler J: Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000, 215: 835-840.CrossRefPubMed
46.
Saadat E, Jobke B, Chu B, Lu Y, Cheng J, Li X, Ries MD, Majumdar S, Link TM: Diagnostic performance of in vivo 3-T MRI for articular cartilage abnormalities in human osteoarthritic knees using histology as standard of reference. Eur Radiol. 2008, 18: 2292-22302. 10.1007/s00330-008-0989-7.PubMedCentralCrossRefPubMed
47.
Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, Hunter TB, Resnick DL: Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol. 2008, 37: 423-431. 10.1007/s00256-008-0446-3.CrossRefPubMed
48.
Leydet-Quilici H, Le Corroller T, Bouvier C, Giorgi R, Argenson JN, Champsaur P, Pham T, de Paula AM, Lafforgue P: Advanced hip osteoarthritis: magnetic resonance imaging aspects and histopathology correlations. Osteoarthritis Cartilage. 2010, 18: 1429-1435. 10.1016/j.joca.2010.08.008.CrossRefPubMed
49.
Sun HB: Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci. 2010, 1211: 37-50. 10.1111/j.1749-6632.2010.05808.x.CrossRefPubMed
50.
Weyand CM, Goronzy JJ: Ectopic germinal center formation in rheumatoid synovitis. Ann N Y Acad Sci. 2003, 987: 140-149. 10.1111/j.1749-6632.2003.tb06042.x.CrossRefPubMed
51.
Bugatti S, Manzo A, Bombardieri M, Vitolo B, Humby F, Kelly S, Montecucco C, Pitzalis C: Synovial tissue heterogeneity and peripheral blood biomarkers. Curr Rheumatol Rep. 2011, 13: 440-448. 10.1007/s11926-011-0201-y.CrossRefPubMed
52.
Manzo A, Paoletti S, Carulli M, Blades MC, Barone F, Yanni G, Fitzgerald O, Bresnihan B, Caporali R, Montecucco C, Uguccioni M, Pitzalis C: Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol. 2005, 35: 1347-1359. 10.1002/eji.200425830.CrossRefPubMed
53.
Corsiero E, Bombardieri M, Manzo A, Bugatti S, Uguccioni M, Pitzalis C: Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases. Immunol Lett. 2012, 145: 62-67. 10.1016/j.imlet.2012.04.013.CrossRefPubMed
54.
Schröder AE, Greiner A, Seyfert C, Berek C: Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc Natl Acad Sci USA. 1996, 93: 221-225. 10.1073/pnas.93.1.221.PubMedCentralCrossRefPubMed
55.
Scheel T, Gursche A, Zacher J, Häupl T, Berek C: V-region gene analysis of locally defined synovial B and plasma cells reveals selected B cell expansion and accumulation of plasma cell clones in rheumatoid arthritis. Arthritis Rheum. 2011, 63: 63-72. 10.1002/art.27767.CrossRefPubMed
56.
Humby F, Bombardieri M, Manzo A, Kelly S, Blades MC, Kirkham B, Spencer J, Pitzalis C: Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 2009, 6: e1-PubMedCentralCrossRefPubMed
57.
McQueen F, Elliott B: B cell lymphoproliferation and organ-directed self-recognition to explain autoimmunity: back to the past. Med Hypotheses. 2010, 75: 328-333. 10.1016/j.mehy.2010.03.015.CrossRefPubMed
58.
Thurlings RM, Wijbrandts CA, Mebius RE, Cantaert T, Dinant HJ, van der Pouw-Kraan TC, Verweij CL, Baeten D, Tak PP: Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype. Arthritis Rheum. 2008, 58: 1582-1589. 10.1002/art.23505.CrossRefPubMed
59.
Cantaert T, Kolln J, Timmer T, van der Pouw Kraan TC, Vandooren B, Thurlings RM, Cañete JD, Catrina AI, Out T, Verweij CL, Zhang Y, Tak PP, Baeten D: B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J Immunol. 2008, 181: 785-794.CrossRefPubMed
60.
Bugatti S, Manzo A, Vitolo B, Fusetti C, Humby F, Caporali R, Pitzalis C, Montecucco C: B cell distribution and activation-induced cytidine deaminase expression in rheumatoid synovitis: clinical and bio-molecular correlates. Ann Rheum Dis. 2011, 70 (Suppl 2): A55-CrossRef
61.
Mo YQ, Dai L, Zheng DH, Zhu LJ, Wei XN, Pessler F, Shen J, Zhang BY: Synovial infiltration with CD79a-positive B cells, but not other B cell lineage markers, correlates with joint destruction in rheumatoid arthritis. J Rheumatol. 2011, 38: 2301-2308. 10.3899/jrheum.110615.CrossRefPubMed
62.
Lanfant-Weybel K, Michot C, Daveau R, Milliez PY, Auquit-Auckbur I, Fardellone P, Brazier M, Mejjad O, Daragon A, Krzanowska K, Jouen F, Tron F, Le Loarer F, Le Loët X, Vittecoq O: Synovium CD20 expression is a potential new predictor of bone erosion progression in very-early arthritis treated by sequential DMARDs monotherapy - A pilot study from the VErA cohort. Joint Bone Spine. 2012, 79: 574-580. 10.1016/j.jbspin.2011.11.006.CrossRefPubMed
63.
Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G: Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012, 122: 1791-1802. 10.1172/JCI60975.PubMedCentralCrossRefPubMed
64.
Manzo A, Bugatti S, Caporali R, Prevo R, Jackson DG, Uguccioni M, Buckley CD, Montecucco C, Pitzalis C: CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. Am J Pathol. 2007, 171: 1549-1562. 10.2353/ajpath.2007.061275.PubMedCentralCrossRefPubMed
65.
Haavardsholm EA, Bøyesen P, ∅stergaard M, Schildvold A, Kvien TK: Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression. Ann Rheum Dis. 2008, 67: 794-800. 10.1136/ard.2007.071977.CrossRefPubMed
66.
Duer-Jensen A, Hørslev-Petersen K, Hetland ML, Bak L, Ejbjerg BJ, Hansen MS, Johansen JS, Lindegaard HM, Vinterberg H, Møller JM, ∅stergaard M: Bone edema on magnetic resonance imaging is an independent predictor of rheumatoid arthritis development in patients with early undifferentiated arthritis. Arthritis Rheum. 2011, 63: 2192-2202. 10.1002/art.30396.CrossRefPubMed
67.
Bugatti S, Caporali R, Manzo A, Sakellariou G, Rossi S, Montecucco C: Ultrasonographic and MRI characterisation of the palindromic phase of rheumatoid arthritis. Ann Rheum Dis. 2012, 71: 625-626. 10.1136/annrheumdis-2011-200077.CrossRefPubMed
68.
Stach CM, Bäuerle M, Englbrecht M, Kronke G, Engelke K, Manger B, Schett G: Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum. 2010, 62: 330-339.PubMed
69.
Marinova-Mutafchieva L, Williams RO, Funa K, Maini RN, Zvaifler NJ: Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis. Arthritis Rheum. 2002, 46: 507-513. 10.1002/art.10126.CrossRefPubMed
70.
Kishimoto Y, Fukumoto S, Nishihara S, Mizumura H, Hirai K, Teshima R: Gene expression relevant to osteoclastogenesis in the synovium and bone marrow of mature rats with collagen-induced arthritis. Rheumatology. 2004, 43: 1496-1503. 10.1093/rheumatology/keh395.CrossRefPubMed
71.
Rodríguez-Palmero M, Pelegrí C, Ferri MJ, Castell M, Franch A, Castellote C: Alterations of lymphocyte populations in lymph nodes but not in spleen during the latency period of adjuvant arthritis. Inflammation. 1999, 23: 153-165. 10.1023/A:1020293012793.CrossRefPubMed
72.
Mandik-Nayak L, Wipke BT, Shih FF, Unanue ER, Allen PM: Despite ubiquitous autoantigen expression, arthritogenic autoantibody response initiates in the local lymph node. Proc Natl Acad Sci USA. 2002, 99: 14368-14373. 10.1073/pnas.182549099.PubMedCentralCrossRefPubMed
73.
Proulx ST, Kwok E, You Z, Beck CA, Shealy DJ, Ritchlin CT, Boyce BF, Xing L, Schwarz EM: MRI and quantification of draining lymph node function in inflammatory arthritis. Ann N Y Acad Sci. 2007, 1117: 106-123. 10.1196/annals.1402.016.CrossRefPubMed
74.
Proulx ST, Kwok E, You Z, Papuga MO, Beck CA, Shealy DJ, Ritchlin CT, Awad HA, Boyce BF, Xing L, Schwarz EM: Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory arthritis in mice by in vivo magnetic resonance imaging and microfocal computed tomography. Arthritis Rheum. 2007, 56: 4024-4037. 10.1002/art.23128.PubMedCentralCrossRefPubMed
75.
Guo R, Zhou Q, Proulx ST, Wood R, Ji RC, Ritchlin CT, Pytowski B, Zhu Z, Wang YJ, Schwarz EM, Xing L: Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis. Arthritis Rheum. 2009, 60: 2666-2676. 10.1002/art.24764.PubMedCentralCrossRefPubMed
76.
Li J, Kuzin I, Moshkani S, Proulx ST, Xing L, Skrombolas D, Dunn R, Sanz I, Schwarz EM, Bottaro A: Expanded CD23(+)/CD21(hi) B cells in inflamed lymph nodes are associated with the onset of inflammatory-erosive arthritis in TNF-transgenic mice and are targets of anti-CD20 therapy. J Immunol. 2010, 184: 6142-6150. 10.4049/jimmunol.0903489.PubMedCentralCrossRefPubMed
77.
Li J, Zhou Q, Wood RW, Kuzin I, Bottaro A, Ritchlin CT, Xing L, Schwarz EM: CD23(+)/CD21(hi) B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice. Arthritis Res Ther. 2011, 13: R138-10.1186/ar3452.PubMedCentralCrossRefPubMed
78.
Moshkani S, Kuzin II, Adewale F, Jansson J, Sanz I, Schwarz EM, Bottaro A: CD23+ CD21(high) CD1d(high) B cells in inflamed lymph nodes are a locally differentiated population with increased antigen capture and activation potential. J Immunol. 2012, 188: 5944-5953. 10.4049/jimmunol.1103071.PubMedCentralCrossRefPubMed
79.
Nosanchuk JS, Schnitzer B: Follicular hyperplasia in lymph nodes from patients with rheumatoid arthritis. A clinicopathologic study. Cancer. 1969, 24: 243-254.CrossRefPubMed
80.
Willkens RF, Roth GF, Husby G, Williams RC: Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma. Ann Rheum Dis. 1980, 39: 147-151. 10.1136/ard.39.2.147.PubMedCentralCrossRefPubMed
81.
van Baarsen LGM, de Hair MJH, Ramwadhdoebe TH, van de Sande M, Zijlstra IJAJ, Maas M, Gerlag DM, Tak PP: Investigating the cellular composition of lymph nodes in preclinical and early inflammatory arthritis: a feasibility study. Ann Rheum Dis. 2012, 71 (Suppl 1): A20-CrossRef
82.
de Hair MJ, Zijlstra IA, Boumans MJ, van de Sande MG, Maas M, Gerlag DM, Tak PP: Hunting for the pathogenesis of rheumatoid arthritis: core-needle biopsy of inguinal lymph nodes as a new research tool. Ann Rheum Dis. 2012, 71: 1911-1912. 10.1136/annrheumdis-2012-201540.CrossRefPubMed
83.
Bromley M, Woolley DE: Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint. Arthritis Rheum. 1984, 27: 968-975. 10.1002/art.1780270902.CrossRefPubMed
84.
Kaneko M, Tomita T, Nakase T, Ohsawa Y, Seki H, Takeuchi E, Takano H, Shi K, Takahi K, Kominami E, Uchiyama Y, Yoshikawa H, Ochi T: Expression of proteinases and inflammatory cytokines in subchondral bone regions in the destructive joint of rheumatoid arthritis. Rheumatology. 2001, 40: 247-255. 10.1093/rheumatology/40.3.247.CrossRefPubMed
85.
Görtz B, Hayer S, Redlich K, Zwerina J, Tohidast-Akrad M, Tuerk B, Hartmann C, Kollias G, Steiner G, Smolen JS, Schett G: Arthritis induces lymphocytic bone marrow inflammation and endosteal bone formation. J Bone Miner Res. 2004, 19: 990-998. 10.1359/JBMR.040205.CrossRefPubMed
86.
Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB, Gravallese EM: Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res. 2009, 24: 1572-1585. 10.1359/jbmr.090320.CrossRefPubMed
87.
Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Stach C, Schett G: Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion. Ann Rheum Dis. 2011, 70: 1587-1593. 10.1136/ard.2010.148395.CrossRefPubMed
88.
Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma 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
89.
Bobbio-Pallavicini F, Caporali R, Bugatti S, Montecucco C: What can we learn from treatment-induced changes in rheumatoid factor and anticitrullinated peptide antibodies?. J Rheumatol. 2008, 35: 1903-1905.PubMed
Metadata
Title
Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective
Authors
Serena Bugatti
Antonio Manzo
Roberto Caporali
Carlomaurizio Montecucco
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2012
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4115

Other articles of this Issue 6/2012

Arthritis Research & Therapy 6/2012 Go to the issue

Research article

Predictors of use of pain medications for persistent knee pain after primary Total Knee Arthroplasty: a cohort study using an institutional joint registry

Research article

The role of inflammation, the autonomic nervous system and classical cardiovascular disease risk factors on subendocardial viability ratio in patients with RA: a cross-sectional and longitudinal study

Research article

IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritis

Research article

Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study

Research article

Disease activity and cognition in rheumatoid arthritis: an open label pilot study

Research article

Suboptimal cardiovascular risk factor identification and management in patients with rheumatoid arthritis: a cohort analysis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits