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 3/2009

Open Access 01-06-2009 | Research article

Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor

Authors: M Margarida Souto-Carneiro, Vijayabhanu Mahadevan, Kazuki Takada, Ruth Fritsch-Stork, Toshihiro Nanki, Margaret Brown, Thomas A Fleisher, Mildred Wilson, Raphaela Goldbach-Mansky, Peter E Lipsky

Published in: Arthritis Research & Therapy | Issue 3/2009

Login to get access

Abstract

Introduction

Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear.

Methods

The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab.

Results

RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD+CD27+ memory B cells than healthy individuals, whereas post-switch IgD-CD27+ accumulate with increased disease duration. Notably, both pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD+CD27 memory B cells in the peripheral blood.

Conclusions

The data suggest that decreases in peripheral blood IgD+CD27+ pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF.
Appendix
Available only for authorised users
Literature
1.
2.
Kotzin BL: The role of B cells in the pathogenesis of rheumatoid arthritis. J Rheumatol Suppl. 2005, 73: 14-18.PubMed
3.
Krenn V, Souto-Carneiro MM, Kim HJ, Berek C, Starostik P, Konig A, Harms H, Müller-Hermelink HK: Histopathology and molecular pathology of synovial B-lymphocytes in rheumatoid arthritis. Histol Histopathol. 2000, 15: 791-798.PubMed
4.
Timmer TC, Baltus B, Vondenhoff M, Huizinga TW, Tak PP, Verweij CL, Mebius RE, Pouw Kraan van der TC: Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis. Arthritis Rheum. 2007, 56: 2492-2502.CrossRefPubMed
5.
Canete JD, Celis R, Moll C, Izquierdo E, Marsal S, Sanmarti R, Palacin A, Lora D, de la Cruz J, Pablos JL: Clinical significance of synovial lymphoid neogenesis and its reversal after anti-TNF-{alpha} therapy in rheumatoid arthritis. Ann Rheum Dis. 2009, 68: 751-756.CrossRefPubMed
6.
Kim HJ, Krenn V, Steinhauser G, Berek C: Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J Immunol. 1999, 162: 3053-3062.PubMed
7.
Schroder 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.PubMedCentralCrossRefPubMed
8.
Weyand CM, Goronzy JJ: Ectopic germinal center formation in rheumatoid synovitis. Ann N Y Acad Sci. 2003, 987: 140-149.CrossRefPubMed
9.
Edwards JC, Leandro MJ, Cambridge G: B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun. 2005, 8: 175-192.CrossRefPubMed
10.
Maurer D, Fischer GF, Fae I, Majdic O, Stuhlmeier K, Von Jeney N, Holter W, Knapp W: IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset. J Immunol. 1992, 148: 3700-3705.PubMed
11.
Shi Y, Agematsu K, Ochs HD, Sugane K: Functional analysis of human memory B-cell subpopulations: IgD+CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. Clin Immunol. 2003, 108: 128-137.CrossRefPubMed
12.
Werner-Favre C, Bovia F, Schneider P, Holler N, Barnet M, Kindler V, Tschopp J, Zubler RH: IgG subclass switch capacity is low in switched and in IgM-only, but high in IgD+IgM+, post-germinal center (CD27+) human B cells. Eur J Immunol. 2001, 31: 243-249.CrossRefPubMed
13.
Klein U, Rajewsky K, Kuppers R: Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998, 188: 1679-1689.PubMedCentralCrossRefPubMed
14.
Fecteau JF, Cote G, Neron S: A new memory CD27-IgG+ B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation. J Immunol. 2006, 177: 3728-3736.CrossRefPubMed
15.
Jacobi AM, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, Hansen A, Burmester GR, Diamond B, Lipsky PE, Dörner T: Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: Delineation by expression of CD27, IgD, and CD95. Arthritis Rheum. 2008, 58: 1762-1773.CrossRefPubMed
16.
Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J, Lee EH, Milner EC, Sanz I: A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol. 2007, 178: 6624-6633.CrossRefPubMed
17.
Odendahl M, Keitzer R, Wahn U, Hiepe F, Radbruch A, Dörner T, Bunikowski R: Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus. Ann Rheum Dis. 2003, 62: 851-858.PubMedCentralCrossRefPubMed
18.
Hansen A, Odendahl M, Reiter K, Jacobi AM, Feist E, Scholze J, Burmester GR, Lipsky PE, Dörner T: Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2002, 46: 2160-2171.CrossRefPubMed
19.
Anolik JH, Ravikumar R, Barnard J, Owen T, Almudevar A, Milner EC, Miller CH, Dutcher PO, Hadley JA, Sanz I: Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks. J Immunol. 2008, 180: 688-692.CrossRefPubMed
20.
Fekete A, Soos L, Szekanecz Z, Szabo Z, Szodoray P, Barath S, Lakos G: Disturbances in B- and T-cell homeostasis in rheumatoid arthritis: suggested relationships with antigen-driven immune responses. J Autoimmun. 2007, 29: 154-163.CrossRefPubMed
21.
Henneken M, Dorner T, Burmester GR, Berek C: Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther. 2005, 7: R1001-1013.PubMedCentralCrossRefPubMed
22.
Feldmann M: Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol. 2002, 2: 364-371.CrossRefPubMed
23.
Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, Braun J, Reed E, Gjertson D, Singh RR: TNFalpha blockade in human diseases: An overview of efficacy and safety. Clin Immunol. 2008, 126: 121-136.PubMedCentralCrossRefPubMed
24.
Lipsky PE, Heijde van der DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN, Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000, 343: 1594-1602.CrossRefPubMed
25.
26.
27.
Zhang Q, Lu Y, Proulx ST, Guo R, Yao Z, Schwarz EM, Boyce BF, Xing L: Increased lymphangiogenesis in joints of mice with inflammatory arthritis. Arthritis Res Ther. 2007, 9: R118-PubMedCentralCrossRefPubMed
28.
Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F: The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum. 1992, 35: 498-502.CrossRefPubMed
29.
Yazdani-Biuki B, Stadlmaier E, Mulabecirovic A, Brezinschek R, Tilz G, Demel U, Mueller T, Brickmann K, Graninger WB, Brezinschek HP: Blockade of tumour necrosis factor {alpha} significantly alters the serum level of IgG- and IgA-rheumatoid factor in patients with rheumatoid arthritis. Ann Rheum Dis. 2005, 64: 1224-1226.PubMedCentralCrossRefPubMed
30.
Souto-Carneiro MM, Longo NS, Russ DE, Sun HW, Lipsky PE: Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly developed software algorithm, JOINSOLVER. J Immunol. 2004, 172: 6790-6802.CrossRefPubMed
31.
Tak PP, Hintzen RQ, Teunissen JJ, Smeets TJ, Daha MR, van Lier RA, Kluin PM, Meinders AE, Swaak AJ, Breedveld FC: Expression of the activation antigen CD27 in rheumatoid arthritis. Clin Immunol Immunopathol. 1996, 80: 129-138.CrossRefPubMed
32.
Tangye SG, Good KL: Human IgM+CD27+ B cells: memory B cells or "memory" B cells?. J Immunol. 2007, 179: 13-19.CrossRefPubMed
33.
Chong Y, Ikematsu H, Yamaji K, Nishimura M, Nabeshima S, Kashiwagi S, Hayashi J: CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(-) (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances. Int Immunol. 2005, 17: 383-390.CrossRefPubMed
34.
Bende RJ, van Maldegem F, Triesscheijn M, Wormhoudt TA, Guijt R, van Noesel CJ: Germinal centers in human lymph nodes contain reactivated memory B cells. J Exp Med. 2007, 204: 2655-2665.PubMedCentralCrossRefPubMed
35.
Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, Tchernia G, Steiniger B, Staudt LM, Casanova JL, Reynaud CA, Weill JC: Human blood IgM 'memory' B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004, 104: 3647-3654.PubMedCentralCrossRefPubMed
36.
Wehr C, Eibel H, Masilamani M, Illges H, Schlesier M, Peter HH, Warnatz K: A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol. 2004, 113: 161-171.CrossRefPubMed
37.
Gearing AJ, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K: Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature. 1994, 370: 555-557.CrossRefPubMed
38.
Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. 2000, 59: 455-461.PubMedCentralCrossRefPubMed
39.
Prasad KV, Ao Z, Yoon Y, Wu MX, Rizk M, Jacquot S, Schlossman SF: CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein. Proc Natl Acad Sci USA. 1997, 94: 6346-6351.PubMedCentralCrossRefPubMed
40.
Bruhl H, Wagner K, Kellner H, Schattenkirchner M, Schlondorff D, Mack M: Surface expression of CC- and CXC-chemokine receptors on leucocyte subsets in inflammatory joint diseases. Clin Exp Immunol. 2001, 126: 551-559.PubMedCentralCrossRefPubMed
41.
Hansen A, Reiter K, Ziprian T, Jacobi A, Hoffmann A, Gosemann M, Scholze J, Lipsky PE, Dörner T: Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjogren's syndrome. Arthritis Rheum. 2005, 52: 2109-2119.CrossRefPubMed
42.
43.
Schmutz C, Hulme A, Burman A, Salmon M, Ashton B, Buckley C, Middleton J: Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5. Arthritis Res Ther. 2005, 7: R217-229.PubMedCentralCrossRefPubMed
44.
Carlsen HS, Baekkevold ES, Morton HC, Haraldsen G, Brandtzaeg P: Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis. Blood. 2004, 104: 3021-3027.CrossRefPubMed
45.
Katschke KJ, Rottman JB, Ruth JH, Qin S, Wu L, LaRosa G, Ponath P, Park CC, Pope RM, Koch AE: Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis. Arthritis Rheum. 2001, 44: 1022-1032.CrossRefPubMed
46.
Ruschpler P, Lorenz P, Eichler W, Koczan D, Hanel C, Scholz R, Melzer C, Thiesen HJ, Stiehl P: High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis. Arthritis Res Ther. 2003, 5: R241-252.PubMedCentralCrossRefPubMed
47.
Shi K, Hayashida K, Kaneko M, Hashimoto J, Tomita T, Lipsky PE, Yoshikawa H, Ochi T: Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients. J Immunol. 2001, 166: 650-655.CrossRefPubMed
48.
Tsubaki T, Takegawa S, Hanamoto H, Arita N, Kamogawa J, Yamamoto H, Takubo N, Nakata S, Yamada K, Yamamoto S, Yoshie O, Nose M: Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts. Clin Exp Immunol. 2005, 141: 363-371.PubMedCentralCrossRefPubMed
49.
50.
Zlotnik A, Yoshie O: Chemokines: a new classification system and their role in immunity. Immunity. 2000, 12: 121-127.CrossRefPubMed
51.
Flaishon L, Becker-Herman S, Hart G, Levo Y, Kuziel WA, Shachar I: Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration. Blood. 2004, 104: 933-941.CrossRefPubMed
52.
Campbell DJ, Kim CH, Butcher EC: Chemokines in the systemic organization of immunity. Immunol Rev. 2003, 195: 58-71.CrossRefPubMed
53.
Allen CD, Ansel KM, Low C, Lesley R, Tamamura H, Fujii N, Cyster JG: Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol. 2004, 5: 943-952.CrossRefPubMed
54.
Hargreaves DC, Hyman PL, Lu TT, Ngo VN, Bidgol A, Suzuki G, Zou YR, Littman DR, Cyster JG: A coordinated change in chemokine responsiveness guides plasma cell movements. J Exp Med. 2001, 194: 45-56.PubMedCentralCrossRefPubMed
55.
Muehlinghaus G, Cigliano L, Huehn S, Peddinghaus A, Leyendeckers H, Hauser AE, Hiepe F, Radbruch A, Arce S, Manz RA: Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood. 2005, 105: 3965-3971.CrossRefPubMed
56.
De Miguel S, Jover JA, Vadillo C, Judez E, Loza E, Fernandez-Gutierrez B: B cell activation in rheumatoid arthritis patients under infliximab treatment. Clin Exp Rheumatol. 2003, 21: 726-732.PubMed
57.
Gonzalez-Gay MA, Garcia-Unzueta MT, De Matias JM, Gonzalez-Juanatey C, Garcia-Porrua C, Sanchez-Andrade A, Martin J, Llorca J: Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2006, 24: 373-379.PubMed
58.
Klimiuk PA, Sierakowski S, Domyslawska I, Fiedorczyk M, Chwiecko J: Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab. Arch Immunol Ther Exp (Warsz). 2004, 52: 36-42.
59.
Smeets TJ, Kraan MC, van Loon ME, Tak PP: Tumor necrosis factor alpha blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum. 2003, 48: 2155-2162.CrossRefPubMed
60.
Taylor PC, Peters AM, Paleolog E, Chapman PT, Elliott MJ, McCloskey R, Feldmann M, Maini R: Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum. 2000, 43: 38-47.CrossRefPubMed
61.
Ohshima S, Saeki Y, Mima T, Sasai M, Nishioka K, Ishida H, Shimizu M, Suemura M, McCloskey R, Kishimoto T: Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, and white blood cell subset counts in patients with rheumatoid arthritis (RA) after monoclonal anti-TNF alpha antibody therapy. J Clin Immunol. 1999, 19: 305-313.CrossRefPubMed
62.
Lorenz HM, Grunke M, Hieronymus T, Antoni C, Nusslein H, Schaible TF, Manger B, Kalden JR: In vivo blockade of tumor necrosis factor-alpha in patients with rheumatoid arthritis: longterm effects after repeated infusion of chimeric monoclonal antibody cA2. J Rheumatol. 2000, 27: 304-310.PubMed
Metadata
Title
Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor
Authors
M Margarida Souto-Carneiro
Vijayabhanu Mahadevan
Kazuki Takada
Ruth Fritsch-Stork
Toshihiro Nanki
Margaret Brown
Thomas A Fleisher
Mildred Wilson
Raphaela Goldbach-Mansky
Peter E Lipsky
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2009
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2718

Other articles of this Issue 3/2009

Arthritis Research & Therapy 3/2009 Go to the issue

Research article

Identification of novel genetic susceptibility loci for Behçet's disease using a genome-wide association study

Research article

Reduced rates of primary joint replacement for osteoarthritis in Italian and Greek migrants to Australia: the Melbourne Collaborative Cohort Study

Research article

Relationship of compartment-specific structural knee status at baseline with change in cartilage morphology: a prospective observational study using data from the osteoarthritis initiative

Research article

Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts

Research article

Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems

Review

Progress in spondylarthritis. Immunopathogenesis of spondyloarthritis: which cells drive disease?
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