Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
11 Mar 2024
11 Mar 2024
Historique:
received:
04
03
2022
accepted:
04
03
2024
medline:
12
3
2024
pubmed:
12
3
2024
entrez:
12
3
2024
Statut:
epublish
Résumé
In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
Sections du résumé
BACKGROUND
BACKGROUND
In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA.
RESULTS
RESULTS
In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool.
CONCLUSIONS
CONCLUSIONS
Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
Identifiants
pubmed: 38468286
doi: 10.1186/s13059-024-03210-0
pii: 10.1186/s13059-024-03210-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
68Subventions
Organisme : Instituto de Salud Carlos III
ID : PI17/00019
Organisme : Ministerio de Economía y Competitividad
ID : IPT010000-2010-36
Informations de copyright
© 2024. The Author(s).
Références
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205–19.
pubmed: 22150039
doi: 10.1056/NEJMra1004965
O’Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350:2591–602.
pubmed: 15201416
doi: 10.1056/NEJMra040226
Orange DE, et al. RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares. N Engl J Med. 2020;383:218–28.
pubmed: 32668112
pmcid: 7546156
doi: 10.1056/NEJMoa2004114
Zhang F, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019;20:928–42.
pubmed: 31061532
pmcid: 6602051
doi: 10.1038/s41590-019-0378-1
Mitchison NA. T-cell-B-cell cooperation. Nat Rev Immunol. 2004;4:308–12.
pubmed: 15057789
doi: 10.1038/nri1334
van Steenbergen, H.W., Ajeganova, S., Forslind, K., Svensson, B. & van der Helm-van Mil, A.H. The effects of rheumatoid factor and anticitrullinated peptide antibodies on bone erosions in rheumatoid arthritis. Ann Rheum Dis. 2015;74:e3.
Edwards JC, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572–81.
pubmed: 15201414
doi: 10.1056/NEJMoa032534
Keystone E, et al. Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2009;68:216–21.
pubmed: 18388156
doi: 10.1136/ard.2007.085787
Genovese MC, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005;353:1114–23.
pubmed: 16162882
doi: 10.1056/NEJMoa050524
Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol. 2017;18:76.
pubmed: 28449694
pmcid: 5406920
doi: 10.1186/s13059-017-1207-1
Petersone L, et al. T Cell/B cell collaboration and autoimmunity: an intimate relationship. Front Immunol. 2018;9:1941.
pubmed: 30210496
pmcid: 6119692
doi: 10.3389/fimmu.2018.01941
Calis JJ, Rosenberg BR. Characterizing immune repertoires by high throughput sequencing: strategies and applications. Trends Immunol. 2014;35:581–90.
pubmed: 25306219
pmcid: 4390416
doi: 10.1016/j.it.2014.09.004
Rubelt F, et al. Adaptive Immune Receptor Repertoire Community recommendations for sharing immune-repertoire sequencing data. Nat Immunol. 2017;18:1274–8.
pubmed: 29144493
pmcid: 5790180
doi: 10.1038/ni.3873
Emerson RO, et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat Genet. 2017;49:659–65.
pubmed: 28369038
doi: 10.1038/ng.3822
Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988;334:395–402.
pubmed: 3043226
doi: 10.1038/334395a0
Schatz DG, Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nat Rev Immunol. 2011;11:251–63.
pubmed: 21394103
doi: 10.1038/nri2941
Trück J, Eugster A, Barennes P, Tipton CM, Luning Prak ET, Bagnara D, et al. Biological controls for standardization and interpretation of adaptive immune receptor repertoire profiling. eLife. 2021;10:e66274. https://doi.org/10.7554/eLife.66274 .
Fischer DS, Wu Y, Schubert B, Theis FJ. Predicting antigen specificity of single T cells based on TCR CDR3 regions. Mol Syst Biol. 2020;16: e9416.
pubmed: 32779888
pmcid: 7418512
doi: 10.15252/msb.20199416
Rossjohn J, et al. T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol. 2015;33:169–200.
pubmed: 25493333
doi: 10.1146/annurev-immunol-032414-112334
De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015;15:137–48.
pubmed: 25656706
pmcid: 4399774
doi: 10.1038/nri3804
Duarte JH. Functional switching. Nat Immunol. 2016;17:S12–S12.
doi: 10.1038/ni.3607
Lu LL, Suscovich TJ, Fortune SM, Alter G. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol. 2018;18:46–61.
pubmed: 29063907
doi: 10.1038/nri.2017.106
Bashford-Rogers RJM, et al. Analysis of the B cell receptor repertoire in six immune-mediated diseases. Nature. 2019;574:122–6.
pubmed: 31554970
pmcid: 6795535
doi: 10.1038/s41586-019-1595-3
Georgiou G, et al. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol. 2014;32:158–68.
pubmed: 24441474
pmcid: 4113560
doi: 10.1038/nbt.2782
Cui JH, et al. TCR repertoire as a novel indicator for immune monitoring and prognosis assessment of patients with cervical cancer. Front Immunol. 2018;9:2729.
pubmed: 30524447
pmcid: 6262070
doi: 10.3389/fimmu.2018.02729
Minervina AA, Komech EA, Titov A, Bensouda Koraichi M, Rosati E, Mamedov IZ, et al. Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection. eLife. 2021;10:e63502. https://doi.org/10.7554/eLife.63502 .
Page DB, et al. Deep Sequencing of T-cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy. Cancer Immunol Res. 2016;4:835–44.
pubmed: 27587469
pmcid: 5064839
doi: 10.1158/2326-6066.CIR-16-0013
Liu X, et al. T cell receptor β repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis. 2019;78:1070–8.
pubmed: 31101603
doi: 10.1136/annrheumdis-2019-215442
Pollastro S, et al. Non-response to rituximab therapy in rheumatoid arthritis is associated with incomplete disruption of the B cell receptor repertoire. Ann Rheum Dis. 2019;78:1339–45.
pubmed: 31217169
doi: 10.1136/annrheumdis-2018-214898
Han J, Lotze MT. The adaptome as biomarker for assessing cancer immunity and immunotherapy. Methods Mol Biol. 2020;2055:369–97.
pubmed: 31502161
doi: 10.1007/978-1-4939-9773-2_17
Puelma Touzel M, Walczak AM, Mora T. Inferring the immune response from repertoire sequencing. PLoS Comput Biol. 2020;16: e1007873.
pubmed: 32348312
pmcid: 7213749
doi: 10.1371/journal.pcbi.1007873
Lewis, M.J., et al. Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes. Cell Rep. 2019;28:2455–2470 e2455.
Rosati E, et al. Overview of methodologies for T-cell receptor repertoire analysis. BMC Biotechnol. 2017;17:61.
pubmed: 28693542
pmcid: 5504616
doi: 10.1186/s12896-017-0379-9
Glanville J, et al. Identifying specificity groups in the T cell receptor repertoire. Nature. 2017;547:94–8.
pubmed: 28636589
pmcid: 5794212
doi: 10.1038/nature22976
Zhang W, et al. PIRD: Pan Immune Repertoire Database. Bioinformatics. 2020;36:897–903.
pubmed: 31373607
doi: 10.1093/bioinformatics/btz614
Huang H, Wang C, Rubelt F, Scriba TJ, Davis MM. Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening. Nat Biotechnol. 2020;38:1194–202.
pubmed: 32341563
pmcid: 7541396
doi: 10.1038/s41587-020-0505-4
Wardemann H, et al. Predominant autoantibody production by early human B cell precursors. Science. 2003;301:1374–7.
pubmed: 12920303
doi: 10.1126/science.1086907
Doorenspleet ME, et al. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann Rheum Dis. 2014;73:756.
pubmed: 23606709
doi: 10.1136/annrheumdis-2012-202861
Tak PP, et al. Dominant B cell receptor clones in peripheral blood predict onset of arthritis in individuals at risk for rheumatoid arthritis. Ann Rheum Dis. 2017;76:1924.
pubmed: 28790026
doi: 10.1136/annrheumdis-2017-211351
Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol. 2020;16:145–54.
pubmed: 32066940
doi: 10.1038/s41584-020-0373-9
Alivernini S, et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nat Med. 2020;26:1295–306.
pubmed: 32601335
doi: 10.1038/s41591-020-0939-8
Haringman JJ, et al. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005;64:834–8.
pubmed: 15576415
doi: 10.1136/ard.2004.029751
Kuo D, Ding J, Cohn IS, Zhang F, Wei K, Rao DA, et al. HBEGF+ macrophages in rheumatoid arthritis induce fibroblast invasiveness. Sci Translational Med. 2019;11(491):eaau8587. https://doi.org/10.1126/scitranslmed.aau8587 .
Onuora S. Experimental arthritis: Anti-TNF kills the macrophage response. Nat Rev Rheumatol. 2018;14:64.
pubmed: 29362465
Shen P, Fillatreau S. Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015;15:441–51.
pubmed: 26065586
doi: 10.1038/nri3857
Julià A, et al. Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis. Arthritis Res Ther. 2020;22:196.
pubmed: 32843099
pmcid: 7446220
doi: 10.1186/s13075-020-02287-9
Elliott SE, et al. B cells in rheumatoid arthritis synovial tissues encode focused antibody repertoires that include antibodies that stimulate macrophage TNF-α production. Clin Immunol. 2020;212: 108360.
pubmed: 32035179
pmcid: 7327984
doi: 10.1016/j.clim.2020.108360
Grau-Expósito J, et al. Peripheral and lung resident memory T cell responses against SARS-CoV-2. Nat Commun. 2021;12:3010.
pubmed: 34021148
pmcid: 8140108
doi: 10.1038/s41467-021-23333-3
Vabret N, et al. Immunology of COVID-19: Current State of the Science. Immunity. 2020;52:910–41.
pubmed: 32505227
pmcid: 7200337
doi: 10.1016/j.immuni.2020.05.002
Humby F, et al. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 2009;6: e1.
pubmed: 19143467
pmcid: 2621263
doi: 10.1371/journal.pmed.0060001
Al Kindi MA, et al. Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides. J Autoimmun. 2015;57:77–81.
pubmed: 25577500
doi: 10.1016/j.jaut.2014.12.005
Guggino G, et al. Downregulation of miRNA17-92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis. Arthritis Res Ther. 2018;20:236.
pubmed: 30348222
pmcid: 6235230
doi: 10.1186/s13075-018-1740-7
Mo W-X, et al. Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis. Ann Rheum Dis. 2017;76:2075–84.
pubmed: 28866647
doi: 10.1136/annrheumdis-2016-211069
Jiang X, et al. Comprehensive TCR repertoire analysis of CD4(+) T-cell subsets in rheumatoid arthritis. J Autoimmun. 2020;109: 102432.
pubmed: 32115259
doi: 10.1016/j.jaut.2020.102432
Trouw LA, Pickering MC, Blom AM. The complement system as a potential therapeutic target in rheumatic disease. Nat Rev Rheumatol. 2017;13:538–47.
pubmed: 28794515
doi: 10.1038/nrrheum.2017.125
Gravina G, Erlandsson M, Bossios A, Ekerljung L, Malmhäll C. Low Serum Levels of Immunoglobulin D Recognize Autoantibody Production in Rheumatoid Arthritis. J Mol Sci. 2018;2:5.
Ge C, Holmdahl R. The structure, specificity and function of anti-citrullinated protein antibodies. Nat Rev Rheumatol. 2019;15:503–8.
pubmed: 31253945
doi: 10.1038/s41584-019-0244-4
Kongpachith S, et al. Affinity maturation of the anti-citrullinated protein antibody paratope drives epitope spreading and polyreactivity in rheumatoid arthritis. Arthritis Rheumatol. 2019;71:507–17.
pubmed: 30811898
pmcid: 6519961
doi: 10.1002/art.40760
Titcombe PJ, et al. Pathogenic citrulline-multispecific B cell receptor clades in rheumatoid arthritis. Arthritis Rheumatol. 2018;70:1933–45.
pubmed: 29927106
pmcid: 6261688
doi: 10.1002/art.40590
Greiff V, Miho E, Menzel U, Reddy ST. Bioinformatic and statistical analysis of adaptive immune repertoires. Trends Immunol. 2015;36:738–49.
pubmed: 26508293
doi: 10.1016/j.it.2015.09.006
Finak G, et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015;16:278.
pubmed: 26653891
pmcid: 4676162
doi: 10.1186/s13059-015-0844-5
Zhu Q, Rui K, Wang S, Tian J. Advances of Regulatory B Cells in Autoimmune Diseases. Front Immunol. 2021;12: 592914.
pubmed: 33936028
pmcid: 8082147
doi: 10.3389/fimmu.2021.592914
Zacca ER, et al. PD-L1(+) Regulatory B cells are significantly decreased in rheumatoid arthritis patients and increase after successful treatment. Front Immunol. 2018;9:2241.
pubmed: 30327652
pmcid: 6174216
doi: 10.3389/fimmu.2018.02241
Ishigaki K, et al. Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients. Sci Rep. 2015;5:12937.
pubmed: 26245356
pmcid: 4542667
doi: 10.1038/srep12937
Klarenbeek PL, et al. Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease. Ann Rheum Dis. 2012;71:1088.
pubmed: 22294635
doi: 10.1136/annrheumdis-2011-200612
Sakurai K, et al. HLA-DRB1 shared epitope alleles and disease activity are correlated with reduced t cell receptor repertoire diversity in CD4+ T cells in rheumatoid arthritis. J Rheumatol. 2018;45:905–14.
pubmed: 29657145
doi: 10.3899/jrheum.170909
Dendrou CA, Petersen J, Rossjohn J, Fugger L. HLA variation and disease. Nat Rev Immunol. 2018;18:325–39.
pubmed: 29292391
doi: 10.1038/nri.2017.143
Laki J, et al. Very high levels of anti-citrullinated protein antibodies are associated with HLA-DRB1*15 non-shared epitope allele in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64:2078–84.
pubmed: 22307773
doi: 10.1002/art.34421
Pitzalis C, Choy EHS, Buch MH. Transforming clinical trials in rheumatology: towards patient-centric precision medicine. Nat Rev Rheumatol. 2020;16:590–9.
pubmed: 32887976
doi: 10.1038/s41584-020-0491-4
Kingsmore SF, Lindquist IE, Mudge J, Gessler DD, Beavis WD. Genome-wide association studies: progress and potential for drug discovery and development. Nat Rev Drug Discov. 2008;7:221–30.
pubmed: 18274536
pmcid: 2853477
doi: 10.1038/nrd2519
Julia A, et al. Risk variants for psoriasis vulgaris in a large case-control collection and association with clinical subphenotypes. Hum Mol Genet. 2012;21:4549–57.
pubmed: 22814393
doi: 10.1093/hmg/dds295
Kay, J. & Upchurch, K.S. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology. 2012;51:vi5-vi9.
van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998;41:1845–50.
pubmed: 9778226
doi: 10.1002/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K
Shugay M, et al. Towards error-free profiling of immune repertoires. Nat Methods. 2014;11:653–5.
pubmed: 24793455
doi: 10.1038/nmeth.2960
Bolotin DA, et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods. 2015;12:380–1.
pubmed: 25924071
doi: 10.1038/nmeth.3364
Lefranc M-P, et al. IMGT®, the international ImMunoGeneTics information system® 25 years on. Nucleic Acids Res. 2015;43:D413–22.
pubmed: 25378316
doi: 10.1093/nar/gku1056
Liao Y, Smyth GK, Shi W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 2013;41: e108.
pubmed: 23558742
pmcid: 3664803
doi: 10.1093/nar/gkt214
Purcell S, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.
pubmed: 17701901
pmcid: 1950838
doi: 10.1086/519795
Jia X, et al. Imputing amino acid polymorphisms in human leukocyte antigens. PLoS ONE. 2013;8: e64683.
pubmed: 23762245
pmcid: 3675122
doi: 10.1371/journal.pone.0064683
Shoukat MS, et al. Use of machine learning to identify a T cell response to SARS-CoV-2. Cell Rep Med. 2021;2: 100192.
pubmed: 33495756
pmcid: 7816879
doi: 10.1016/j.xcrm.2021.100192
Kaplinsky J, Arnaout R. Robust estimates of overall immune-repertoire diversity from high-throughput measurements on samples. Nat Commun. 2016;7:11881.
pubmed: 27302887
pmcid: 4912625
doi: 10.1038/ncomms11881
Smith TF, Waterman MS. Identification of common molecular subsequences. J Mol Biol. 1981;147:195–7.
pubmed: 7265238
doi: 10.1016/0022-2836(81)90087-5
Smillie, C.S., et al. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell. 2019;178:714–730 e722.
Hochberg Y, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med. 1990;9:811–8.
pubmed: 2218183
doi: 10.1002/sim.4780090710
Nazarov VI, et al. tcR: an R package for T cell receptor repertoire advanced data analysis. BMC Bioinformatics. 2015;16:175.
pubmed: 26017500
pmcid: 4445501
doi: 10.1186/s12859-015-0613-1
Csardi G, Nepusz T. The igraph software package for complex network research. InterJournal Complex Syst. 2006;1695(5):1–9.
Aterido A, et al. Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis. Ann Rheum Dis. 2019;78:355.
doi: 10.1136/annrheumdis-2018-214158
Levenshtein VI. Binary codes capable of correcting deletions, insertions and reversals. Soviet Physics Doklady. 1966;10:707–10.
Hamming RW. Error detecting and error correcting codes. Bell System Tech J. 1950;29:147–60.
doi: 10.1002/j.1538-7305.1950.tb00463.x
Miron M, et al. Maintenance of the human memory T cell repertoire by subset and tissue site. Genome Med. 2021;13:100.
pubmed: 34127056
pmcid: 8204429
doi: 10.1186/s13073-021-00918-7
Bodenhofer U, Bonatesta E, Horejš-Kainrath C, Hochreiter S. msa: an R package for multiple sequence alignment. Bioinformatics. 2015;31:3997–9.
pubmed: 26315911
doi: 10.1093/bioinformatics/btv494
Wagih O. ggseqlogo: a versatile R package for drawing sequence logos. Bioinformatics. 2017;33:3645–7.
pubmed: 29036507
doi: 10.1093/bioinformatics/btx469
Aterido, A., et al. Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes. Gene Expression Omnibus. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE256256 (2024).
Aterido, A., et al. Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes. Github. 2024. https://github.com/Rheumatology-Research-Group/AIRR-RA .
Aterido, A., et al. Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes. Zenodo. 2024;10.5281/zenodo.10641095.