ORIGINAL RESEARCH

Long-term effect of high cyclophosphamide doses on the repertoire of T-cell receptors of peripheral blood T-lymphocytes in patients with autoimmune vasculitis

Merzlyak EM1, Kasatskaya SA1, Sosnovskaya AV2, Israelson MA, Staroverov DB, Nakonechnaya TO, Novikov PI2, Chudakov DM, Britanova OV
About authors

1 Group of structural Organization of T-cell Immunity, Department of Adaptive Immunity Genomics, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow

2 I. M. Sechenov First Moscow State Medical University, Moscow, Russia

Correspondence should be addressed: Olga V. Britanova
ul. Miklukho-Maklaya, d. 16/10, Moscow, Russia, 117997; moc.liamg@natirblo

About paper

Funding: this work was supported by the Russian Science Foundation (Grant No. 16-15-00149). Equipment used in the study was provided by the shared facility of the Institute of Bioorganic Chemistry (the facility is supported by the Ministry of Education and Science of the Russian Federation, project ID RFMEFI62117X0018).

All authors' contribution to this work is equal: selection and analysis of literature, research planning, data collection, analysis, and interpretation, drafting of a manuscript, editing.

Received: 2017-10-04 Accepted: 2017-10-25 Published online: 2018-01-14
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  1. Brodsky RA. High dose cyclophosphamide treatment for autoimmune disorders. ScientificWorldJournal. 2002 Jun 28; 2: 1808–15. DOI: 10.1100/tsw.2002.863.
  2. DeZern AE, Styler MJ, Drachman DB, Hummers LK, Jones RJ, Brodsky RA Repeated treatment with high dose cyclophosphamide for severe autoimmune diseases. Am J Blood Res. 2013; 3 (1): 84–90.
  3. Gladstone DE, Golightly MG, Brannagan TH 3rd. High dose cyclophosphamide preferentially targets naïve T (CD45/CD4/RA+) cells in CIDP and MS patients. J Neuroimmunol. 2007 Oct; 190 (1–2): 121–6. DOI: 10.1016/j.jneuroim.2007.07.005.
  4. Britanova OV, Shugay M, Merzlyak EM, Staroverov DB, Putintseva EV, Turchaninova MA et al. Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians. J Immunol. 2016 Jun 15; 196 (12): 5005–13. DOI: 10.4049/jimmunol.1600005.
  5. Wilde B, Thewissen M, Damoiseaux J, van Paassen P, Witzke O, Tervaert JWC. T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells? Arthritis Res Ther. 2010; 12 (1): 204. DOI: 10.1186/ar2923.
  6. McKinney EF, Willcocks LC, Broecker V, Smith KGC. The immunopathology of ANCA-associated vasculitis. Semin Immunopathol. 2014 Jul; 36 (4): 461–78. DOI: 10.1007/s00281-014-0436-6.
  7. Giscombe R, Wang XB, Kakoulidou M, Lefvert AK. Characterization of the expanded T-cell populations in patients with Wegener's granulomatosis. J Intern Med. 2006 Sep; 260 (3): 224–30. DOI: 10.1111/j.1365-2796.2006.01688.x.
  8. Ruth AJ, Kitching AR, Kwan RY, Odobasic D, Ooi JD, Timoshanko J et al. Anti-neutrophil cytoplasmic antibodies and effector CD4+ cells play nonredundant roles in anti-myeloperoxidase crescentic glomerulonephritis. J Am Soc Nephrol. 2006 Jul; 17 (7): 1940–9. DOI: 10.1681/ASN.2006020108.
  9. Kanakry CG, Ganguly S, Zahurak M, Bolaños-Meade J, Thoburn C, Perkins B et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med. 2013 Nov 13; 5 (211): 211ra157. DOI: 10.1126/scitranslmed.3006960.
  10. Kanakry CG, Coffey DG, Towlerton AM, Vulic A, Storer BE, Chou J et al. Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide. JCI Insight. 2016; 1 (5): e86252. DOI: 10.1172/jci.insight.86252.
  11. Britanova OV, Putintseva EV, Shugay M, Merzlyak EM, Turchaninova MA, Staroverov DB et al. Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol. 2014 Mar 15; 192 (6): 2689–98. PubMed PMID:24510963 doi: 10.4049/jimmunol.1302064.
  12. Shugay M, Britanova OV, Merzlyak EM, Turchaninova MA, Mamedov IZ, Tuganbaev TR et al. Towards error-free profiling of immune repertoires. Nat Methods. 2014 Jun; 11 (6): 653–5. DOI: 10.1038/nmeth.2960.
  13. Shugay M, Bagaev DV, Turchaninova MA, Bolotin DA, Britanova OV, Putintseva EV et al. VD Jtools: Unifying Post-analysis of T Cell Receptor Repertoires. PLoS Comput Biol. 2015 Nov 25; 11 (11): e1004503. DOI: 10.1371/journal.pcbi.1004503.
  14. Bolotin DA, Poslavsky S, Mitrophanov I, Shugay M, Mamedov I, Putintseva E et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods. 2015 May; 12 (5): 380–1. DOI: 10.1038/nmeth.3364. 
15. Egorov ES, Merzlyak EM, Shelenkov AA, Britanova OV, Sharonov GV, Staroverov DB et al. Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers. J Immunol. 2015; 194 (12): 6155–63. DOI: 10.4049/jimmunol.1500215.
  15. Pogorelyy MV, Elhanati Y, Marcou Q, Sycheva AL, Komech EA, Nazarov VI et al. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires. PLoS Comput Biol. 2017 Jul 6; 13 (7): e1005572. DOI: 10.1371/journal.pcbi.1005572.
  16. Grunewald J, Halapi E, Wahlström J, Giscombe R, Nityanand S, Sanjeevi C et al. T-cell expansions with conserved T-cell receptor beta chain motifs in the peripheral blood of HLA-DRB1*0401 positive patients with necrotizing vasculitis. Blood. 1998; 92 (10): 3737–44.
  17. Müschen M, Warskulat U, Perniok A, Even J, Moers C, Kismet B et al. Involvement of Soluble CD95 in Churg-Strauss Syndrome. Am J Pathol. 1999 Sep; 155 (3): 915–25. DOI: 10.1016/S0002-9440(1)65191-7.
  18. Link CS, Eugster A, Heidenreich F, Rücker-Braun E, Schmiedgen M, Oelschlägel U et al. Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8+ T cell receptor alpha repertoire following allogeneic transplantation. Clin Exp Immunol. 2016 Jun; 184 (3): 389–402. DOI: 10.1111/cei.12770.
  19. Ruggiero E, Nicolay JP, Fronza R, Arens A, Paruzynski A, Nowrouzi A et al. High-resolution analysis of the human T-cell receptor repertoire. Nat Commun. 2015 Sep 1; 6: 8081. DOI: 10.1038/ncomms9081.
  20. Faham M, Carlton V, Moorhead M, Zheng J, Klinger M, Pepin F et al. Discovery of T Cell Receptor β Motifs Specific to HLA-B27-Positive Ankylosing Spondylitis by Deep Repertoire Sequence Analysis. Arthritis Rheumatol. 2017 Apr; 69 (4): 774–84. DOI: 10.1002/art.40028.
  21. Komech Е, Zvyagin I, Shmidt E, Klimenko A, Shostak N, Mamedov I, Lebedev Y. Shared T-cell clones are found in synovial fluid of patients with ankylosing spondylitis. In: Abstract book of 12th EJI-EFIS Tatra Immunology Conference; 2016 Sep 3–7; Strbske Pleso, Slovakia. p. 39.
  22. Guida G, Vallario A, Stella S, Boita M, Circosta P, Mariani S et al. Clonal CD8+ TCR-Vbeta expanded populations with effector memory phenotype in Churg Strauss syndrome. Clin Immunol. 2008 Jul; 128 (1): 94–102. DOI: 10.1016/j.clim.2008.03.505.