Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 53, Issue 2, pp 277–290 | Cite as

Lymphocytes as Biomarkers of Therapeutic Response in Rheumatic Autoimmune Diseases, Is It a Realistic Goal?

  • Kristina Schreiber
  • Gaetane Nocturne
  • Divi Cornec
  • Claire I. Daïen
Article

Abstract

Many therapies are available for patients with rheumatoid arthritis (RA) while biological therapies have limited effects in patients with systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). In both cases, biomarkers predicting drug response would be very useful to guide clinicians in their choice. We performed a systematic review to evaluate the value of lymphocyte phenotyping as a marker of therapeutic response. Of the 1063 articles retrieved, 39 fulfilled inclusion criteria and were included in the present review (25 for RA, 10 for SLE, and 4 for pSS). Lymphocyte phenotyping was described as a biomarker of therapeutic response in many studies, but most results could not be confirmed by independent teams using multivariate analysis. The most consistent result might be the association between rituximab response and the levels of memory B cells before therapy, although some studies were controversial. Thus, lymphocyte phenotyping cannot yet be proposed as a biomarker of response in rheumatic autoimmune diseases. The lack of reproducibility between studies may be explained by technical issues influencing lymphocyte phenotyping so standardization procedures should be developed for future studies. The patients’ characteristics vary between studies, and large population studies, including a wide range of patients’ characteristics and biomarkers, are required to provide predictive models for clinical outcomes. The use of new flow cytometry techniques such as single-cell mass cytometry technology might also help finder reliable biomarkers in the future.

Keywords

Autoimmune diseases Lymphocyte subsets Rheumatoid arthritis Systemic lupus erythematosus Sjögren’s syndrome Personalized medicine Biomarkers Predictive markers Therapeutic response 

Notes

Acknowledgements

Thanks are due to Sumaiya Hoque for editing the English language.

Compliance with Ethical Standards

Conflicts of Interest

CID has received honoraria from BMS, MSD, Pfizer, Roche-Chugai, and UCB and research grants from MSD, Pfizer, Roche-Chugai, and UCB.

Funding

No funding was received.

Ethical Approval and Informed Consent

This article is a review of studies that fulfilled the ethical standards.

Supplementary material

12016_2017_8614_MOESM1_ESM.docx (59 kb)
Supplementary Table 1 (DOCX 58 kb)

References

  1. 1.
    Lee DM, Weinblatt ME (2001) Rheumatoid arthritis. Lancet 358(9285):903–911. doi: 10.1016/S0140-6736(01)06075-5 CrossRefPubMedGoogle Scholar
  2. 2.
    Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR (2001) Systemic lupus erythematosus. Lancet 357(9261):1027–1032. doi: 10.1016/S0140-6736(00)04239-2 CrossRefPubMedGoogle Scholar
  3. 3.
    Nocturne G, Seror R, Devauchelle-Pensec V, Saraux A, Mariette X, Chiche L (2017) Prevalence of primary Sjogren syndrome: what if Sjogren was right after all? Arthritis Care Research. doi: 10.1002/acr.23223
  4. 4.
    Weisman MH, Moreland LW, Furst DE, Weinblatt ME, Keystone EC, Paulus HE, Teoh LS, Velagapudi RB, Noertersheuser PA, Granneman GR, Fischkoff SA, Chartash EK (2003) Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther 25(6):1700–1721CrossRefPubMedGoogle Scholar
  5. 5.
    Bykerk VP, Ostor AJ, Alvaro-Gracia J, Pavelka K, Ivorra JA, Graninger W, Bensen W, Nurmohamed MT, Krause A, Bernasconi C, Stancati A, Sibilia J (2012) Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. Ann Rheum Dis 71(12):1950–1954. doi: 10.1136/annrheumdis-2011-201087 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepanski LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H (2010) Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis 69(9):1629–1635. doi: 10.1136/ard.2009.119933 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, Cohen S, Luggen M, Shergy W, Nuamah I, Becker JC (2002) Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis & Rheumatism 46(6):1470–1479. doi: 10.1002/art.10294 CrossRefGoogle Scholar
  8. 8.
    Dooley MA, Houssiau F, Aranow C, D’Cruz DP, Askanase A, Roth DA, Zhong ZJ, Cooper S, Freimuth WW, Ginzler EM, Bliss, Study G (2013) Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus 22(1):63–72. doi: 10.1177/0961203312465781 CrossRefPubMedGoogle Scholar
  9. 9.
    Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D, Sanchez-Guerrero J, Schwarting A, Merrill JT, Chatham WW, Stohl W, Ginzler EM, Hough DR, Zhong ZJ, Freimuth W, van Vollenhoven RF, Group B-S (2011) A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis & Rheumatism 63(12):3918–3930. doi: 10.1002/art.30613 CrossRefGoogle Scholar
  10. 10.
    Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G, Group LI (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis & Rheumatism 64(4):1215–1226. doi: 10.1002/art.34359 CrossRefGoogle Scholar
  11. 11.
    Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puechal X, Le Guern V, Sibilia J, Gottenberg JE, Chiche L, Hachulla E, Hatron PY, Goeb V, Hayem G, Morel J, Zarnitsky C, Dubost JJ, Pers JO, Nowak E, Saraux A (2014) Treatment of primary Sjogren syndrome with rituximab: a randomized trial. Ann Intern Med 160(4):233–242. doi: 10.7326/M13-1085 CrossRefPubMedGoogle Scholar
  12. 12.
    Gottenberg JE, Ravaud P, Puechal X, Le Guern V, Sibilia J, Goeb V, Larroche C, Dubost JJ, Rist S, Saraux A, Devauchelle-Pensec V, Morel J, Hayem G, Hatron P, Perdriger A, Sene D, Zarnitsky C, Batouche D, Furlan V, Benessiano J, Perrodeau E, Seror R, Mariette X (2014) Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren syndrome: the JOQUER randomized clinical trial. JAMA : the journal of the American Medical Association 312(3):249–258. doi: 10.1001/jama.2014.7682 CrossRefPubMedGoogle Scholar
  13. 13.
    Moutsopoulos NM, Katsifis GE, Angelov N, Leakan RA, Sankar V, Pillemer S, Wahl SM (2008) Lack of efficacy of etanercept in Sjogren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation. Ann Rheum Dis 67(10):1437–1443. doi: 10.1136/ard.2007.077891 CrossRefPubMedGoogle Scholar
  14. 14.
    van der Heijde D, Aletaha D, Carmona L, Edwards CJ, Kvien TK, Kouloumas M, Machado P, Oliver S, de Wit M, Dougados M (2015) 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis 74(1):8–13. doi: 10.1136/annrheumdis-2014-206350 CrossRefPubMedGoogle Scholar
  15. 15.
    Fedele AL, Tolusso B, Gremese E, Bosello SL, Carbonella A, Canestri S, Ferraccioli G (2014) Memory B cell subsets and plasmablasts are lower in early than in long-standing rheumatoid arthritis. BMC Immunol 15:28. doi: 10.1186/s12865-014-0028-1 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ponchel F, Goeb V, Parmar R, El-Sherbiny Y, Boissinot M, El Jawhari J, Burska A, Vital EM, Harrison S, Conaghan PG, Hensor E, Emery P (2014) An immunological biomarker to predict MTX response in early RA. Ann Rheum Dis 73(11):2047–2053. doi: 10.1136/annrheumdis-2013-203566 CrossRefPubMedGoogle Scholar
  17. 17.
    Kuuliala K, Kuuliala A, Koivuniemi R, Oksanen S, Hamalainen M, Moilanen E, Kautiainen H, Leirisalo-Repo M, Repo H (2015) Constitutive STAT3 phosphorylation in circulating CD4+ T lymphocytes associates with disease activity and treatment response in recent-onset rheumatoid arthritis. PLoS One 10(9):e0137385. doi: 10.1371/journal.pone.0137385 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Citro A, Scrivo R, Martini H, Martire C, De Marzio P, Vestri AR, Sidney J, Sette A, Barnaba V, Valesini G (2015) CD8+ T cells specific to apoptosis-associated antigens predict the response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis. PLoS One 10(6):e0128607. doi: 10.1371/journal.pone.0128607 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Daien CI, Gailhac S, Mura T, Combe B, Hahne M, Morel J (2014) High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study. Arthritis research & therapy 16(2):R95. doi: 10.1186/ar4543 CrossRefGoogle Scholar
  20. 20.
    Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL (2011) Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-alpha therapy. Arthritis research & therapy 13(4):R126. doi: 10.1186/ar3431 CrossRefGoogle Scholar
  21. 21.
    Daien CI, Gailhac S, Audo R, Mura T, Hahne M, Combe B, Morel J (2015) High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis. Rheumatology (Oxford) 54(4):601–608. doi: 10.1093/rheumatology/keu363 CrossRefGoogle Scholar
  22. 22.
    Kikuchi J, Hashizume M, Kaneko Y, Yoshimoto K, Nishina N, Takeuchi T (2015) Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response. Arthritis research & therapy 17:10. doi: 10.1186/s13075-015-0526-4 CrossRefGoogle Scholar
  23. 23.
    Scarsi M, Ziglioli T, Airo P (2010) Decreased circulating CD28-negative T cells in patients with rheumatoid arthritis treated with abatacept are correlated with clinical response. J Rheumatol 37(5):911–916. doi: 10.3899/jrheum.091176 CrossRefPubMedGoogle Scholar
  24. 24.
    Scarsi M, Ziglioli T, Airo P (2011) Baseline numbers of circulating CD28-negative T cells may predict clinical response to abatacept in patients with rheumatoid arthritis. J Rheumatol 38(10):2105–2111. doi: 10.3899/jrheum.110386 CrossRefPubMedGoogle Scholar
  25. 25.
    Gazeau P, Devauchelle-Pensec V, Pochard P, Pers JO, Saraux A, Renaudineau Y, Cornec D (2016) Abatacept efficacy in rheumatoid arthritis is dependent upon baseline blood B-cell levels. Rheumatology (Oxford) 55(6):1138–1140. doi: 10.1093/rheumatology/kev417 CrossRefGoogle Scholar
  26. 26.
    Roll P, Dorner T, Tony HP (2008) Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis & Rheumatism 58(6):1566–1575. doi: 10.1002/art.23473 CrossRefGoogle Scholar
  27. 27.
    Moller B, Aeberli D, Eggli S, Fuhrer M, Vajtai I, Vogelin E, Ziswiler HR, Dahinden CA, Villiger PM (2009) Class-switched B cells display response to therapeutic B-cell depletion in rheumatoid arthritis. Arthritis research & therapy 11(3):R62. doi: 10.1186/ar2686 CrossRefGoogle Scholar
  28. 28.
    Vital EM, Dass S, Rawstron AC, Buch MH, Goeb V, Henshaw K, Ponchel F, Emery P (2010) Management of nonresponse to rituximab in rheumatoid arthritis: predictors and outcome of re-treatment. Arthritis & Rheumatism 62(5):1273–1279. doi: 10.1002/art.27359 CrossRefGoogle Scholar
  29. 29.
    Brezinschek HP, Rainer F, Brickmann K, Graninger WB (2012) B lymphocyte-typing for prediction of clinical response to rituximab. Arthritis research & therapy 14(4):R161. doi: 10.1186/ar3901 CrossRefGoogle Scholar
  30. 30.
    Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y (2011) Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis & Rheumatism 63(12):3692–3701. doi: 10.1002/art.30599 CrossRefGoogle Scholar
  31. 31.
    Tony HP, Roll P, Mei HE, Blumner E, Straka A, Gnuegge L, Dorner T, teams FRs (2015) Combination of B cell biomarkers as independent predictors of response in patients with rheumatoid arthritis treated with rituximab. Clin Exp Rheumatol 33(6):887–894PubMedGoogle Scholar
  32. 32.
    Stradner MH, Dejaco C, Brickmann K, Graninger WB, Brezinschek HP (2016) A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study. Arthritis research & therapy 18:190. doi: 10.1186/s13075-016-1091-1 CrossRefGoogle Scholar
  33. 33.
    Adlowitz DG, Barnard J, Biear JN, Cistrone C, Owen T, Wang W, Palanichamy A, Ezealah E, Campbell D, Wei C, Looney RJ, Sanz I, Anolik JH (2015) Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLoS One 10(6):e0128269. doi: 10.1371/journal.pone.0128269 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Gaujoux-Viala C, Gossec L, Cantagrel A, Dougados M, Fautrel B, Mariette X, Nataf H, Saraux A, Trope S, Combe B, French Society for R (2014) Recommendations of the French Society for Rheumatology for managing rheumatoid arthritis. Joint Bone Spine 81(4):287–297. doi: 10.1016/j.jbspin.2014.05.002 CrossRefPubMedGoogle Scholar
  35. 35.
    Moura RA, Weinmann P, Pereira PA, Caetano-Lopes J, Canhao H, Sousa E, Mourao AF, Rodrigues AM, Queiroz MV, Souto-Carneiro MM, Graca L, Fonseca JE (2010) Alterations on peripheral blood B-cell subpopulations in very early arthritis patients. Rheumatology (Oxford) 49(6):1082–1092. doi: 10.1093/rheumatology/keq029 CrossRefGoogle Scholar
  36. 36.
    Duty JA, Szodoray P, Zheng NY, Koelsch KA, Zhang Q, Swiatkowski M, Mathias M, Garman L, Helms C, Nakken B, Smith K, Farris AD, Wilson PC (2009) Functional anergy in a subpopulation of naive B cells from healthy humans that express autoreactive immunoglobulin receptors. J Exp Med 206(1):139–151. doi: 10.1084/jem.20080611 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lawson CA, Brown AK, Bejarano V, Douglas SH, Burgoyne CH, Greenstein AS, Boylston AW, Emery P, Ponchel F, Isaacs JD (2006) Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology (Oxford) 45(10):1210–1217. doi: 10.1093/rheumatology/kel089 CrossRefGoogle Scholar
  38. 38.
    Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch M, Verburg RJ, Henwood J, Douglas SH, Masurel A, Conaghan P, Gesinde M, Taylor J, Markham AF, Emery P, van Laar JM, Isaacs JD (2002) Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood 100(13):4550–4556. doi: 10.1182/blood-2002-03-0671 CrossRefPubMedGoogle Scholar
  39. 39.
    Leipe J, Grunke M, Dechant C, Reindl C, Kerzendorf U, Schulze-Koops H, Skapenko A (2010) Role of Th17 cells in human autoimmune arthritis. Arthritis & Rheumatism 62(10):2876–2885. doi: 10.1002/art.27622 CrossRefGoogle Scholar
  40. 40.
    Wijbrandts CA, Dijkgraaf MG, Kraan MC, Vinkenoog M, Smeets TJ, Dinant H, Vos K, Lems WF, Wolbink GJ, Sijpkens D, Dijkmans BA, Tak PP (2008) The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium. Ann Rheum Dis 67(8):1139–1144. doi: 10.1136/ard.2007.080440 CrossRefPubMedGoogle Scholar
  41. 41.
    Fort MM, Leach MW, Rennick DM (1998) A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis. J Immunol 161(7):3256–3261PubMedGoogle Scholar
  42. 42.
    Trivedi PP, Roberts PC, Wolf NA, Swanborg RH (2005) NK cells inhibit T cell proliferation via p21-mediated cell cycle arrest. J Immunol 174(8):4590–4597CrossRefPubMedGoogle Scholar
  43. 43.
    Nocturne G, Boudaoud S, Ly B, Pascaud J, Paoletti A, Mariette X (2017) Impact of anti-TNF therapy on NK cells function and on immunosurveillance against B-cell lymphomas. J Autoimmun. doi: 10.1016/j.jaut.2017.02.001
  44. 44.
    Warrington KJ, Takemura S, Goronzy JJ, Weyand CM (2001) CD4+,CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis & Rheumatism 44(1):13–20. doi: 10.1002/1529-0131(200101)44:1<13::AID-ANR3>3.0.CO;2-6 CrossRefGoogle Scholar
  45. 45.
    Namekawa T, Wagner UG, Goronzy JJ, Weyand CM (1998) Functional subsets of CD4 T cells in rheumatoid synovitis. Arthritis & Rheumatism 41(12):2108–2116. doi: 10.1002/1529-0131(199812)41:12<2108::AID-ART5>3.0.CO;2-Q CrossRefGoogle Scholar
  46. 46.
    Park W, Weyand CM, Schmidt D, Goronzy JJ (1997) Co-stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28- T cells. Eur J Immunol 27(5):1082–1090. doi: 10.1002/eji.1830270507 CrossRefPubMedGoogle Scholar
  47. 47.
    Vos K, Thurlings RM, Wijbrandts CA, van Schaardenburg D, Gerlag DM, Tak PP (2007) Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis. Arthritis & Rheumatism 56(3):772–778. doi: 10.1002/art.22400 CrossRefGoogle Scholar
  48. 48.
    Thurlings RM, Vos K, Wijbrandts CA, Zwinderman AH, Gerlag DM, Tak PP (2008) Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis 67(7):917–925. doi: 10.1136/ard.2007.080960 CrossRefPubMedGoogle Scholar
  49. 49.
    Walsh CA, Fearon U, FitzGerald O, Veale DJ, Bresnihan B (2008) Decreased CD20 expression in rheumatoid arthritis synovium following 8 weeks of rituximab therapy. Clin Exp Rheumatol 26(4):656–658PubMedGoogle Scholar
  50. 50.
    Teng YK, Levarht EW, Hashemi M, Bajema IM, Toes RE, Huizinga TW, van Laar JM (2007) Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment. Arthritis & Rheumatism 56(12):3909–3918. doi: 10.1002/art.22967 CrossRefGoogle Scholar
  51. 51.
    Teng YK, Levarht EW, Toes RE, Huizinga TW, van Laar JM (2009) Residual inflammation after rituximab treatment is associated with sustained synovial plasma cell infiltration and enhanced B cell repopulation. Ann Rheum Dis 68(6):1011–1016. doi: 10.1136/ard.2008.092791 CrossRefPubMedGoogle Scholar
  52. 52.
    Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, Richards A, Rauz S, Emery P (2008) Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis 67(11):1541–1544. doi: 10.1136/ard.2007.083865 CrossRefPubMedGoogle Scholar
  53. 53.
    Lacki JK, Mackiewicz SH, Leszczynski P, Muller W (1997) The effect of intravenous cyclophosphamide pulse on peripheral blood lymphocytes in lupus erythematosus patients. Rheumatol Int 17(2):55–60CrossRefPubMedGoogle Scholar
  54. 54.
    Jonsdottir T, Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF (2008) Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann Rheum Dis 67(3):330–334. doi: 10.1136/ard.2007.079095 CrossRefPubMedGoogle Scholar
  55. 55.
    Lindholm C, Borjesson-Asp K, Zendjanchi K, Sundqvist AC, Tarkowski A, Bokarewa M (2008) Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus. J Rheumatol 35(5):826–833PubMedGoogle Scholar
  56. 56.
    Furie R, Stohl W, Ginzler EM, Becker M, Mishra N, Chatham W, Merrill JT, Weinstein A, McCune WJ, Zhong J, Cai W, Freimuth W, Belimumab Study G (2008) Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis research & therapy 10(5):R109. doi: 10.1186/ar2506 CrossRefGoogle Scholar
  57. 57.
    Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, Aranow C, Wellborne FR, Abud-Mendoza C, Hough DR, Pineda L, Migone TS, Zhong ZJ, Freimuth WW, Chatham WW, Group B-S (2012) Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis & Rheumatism 64(7):2328–2337. doi: 10.1002/art.34400 CrossRefGoogle Scholar
  58. 58.
    Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, Moutsopoulos HM (2005) Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis & Rheumatism 52(2):501–513. doi: 10.1002/art.20858 CrossRefGoogle Scholar
  59. 59.
    Anolik JH, Barnard J, Owen T, Zheng B, Kemshetti S, Looney RJ, Sanz I (2007) Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis & Rheumatism 56(9):3044–3056. doi: 10.1002/art.22810 CrossRefGoogle Scholar
  60. 60.
    Iwata S, Saito K, Tokunaga M, Yamaoka K, Nawata M, Yukawa S, Hanami K, Fukuyo S, Miyagawa I, Kubo S, Tanaka Y (2011) Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. J Rheumatol 38(4):633–641. doi: 10.3899/jrheum.100729 CrossRefPubMedGoogle Scholar
  61. 61.
    Reis EA, Athanazio DA, Lima I, Oliveira e Silva N, Andrade JC, Jesus RN, Barbosa LM, Reis MG, Santiago MB (2009) NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int 29(4):469–475. doi: 10.1007/s00296-008-0719-0 CrossRefPubMedGoogle Scholar
  62. 62.
    Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, van Vollenhoven R, Malmstrom V, Trollmo C (2007) Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol 122(1):62–74. doi: 10.1016/j.clim.2006.08.016 CrossRefPubMedGoogle Scholar
  63. 63.
    Delli K, Haacke EA, Kroese FG, Pollard RP, Ihrler S, van der Vegt B, Vissink A, Bootsma H, Spijkervet FK (2016) Towards personalised treatment in primary Sjogren’s syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis 75(11):1933–1938. doi: 10.1136/annrheumdis-2015-208304 CrossRefPubMedGoogle Scholar
  64. 64.
    Cornec D, Costa S, Devauchelle-Pensec V, Jousse-Joulin S, Marcorelles P, Berthelot JM, Chiche L, Hachulla E, Hatron PY, Goeb V, Vittecoq O, Saraux A, Pers JO (2016) Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjogren’s syndrome. J Autoimmun 67:102–110. doi: 10.1016/j.jaut.2015.11.002 CrossRefPubMedGoogle Scholar
  65. 65.
    Cornec D, Jousse-Joulin S, Costa S, Marhadour T, Marcorelles P, Berthelot JM, Hachulla E, Hatron PY, Goeb V, Vittecoq O, Nowak E, Pers JO, Devauchelle-Pensec V, Saraux A (2016) High-grade salivary-gland involvement, assessed by histology or ultrasonography, is associated with a poor response to a single rituximab course in primary Sjogren’s syndrome: data from the TEARS randomized trial. PLoS One 11(9):e0162787. doi: 10.1371/journal.pone.0162787 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Seror R, Nocturne G, Lazure T, Hendel-Chavez H, Desmoulins F, Belkhir R, Ravaud P, Benbijja M, Poirier-Colame V, Taoufik Y, Mariette X (2015) Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sjogren’s syndrome: results of the BELISS study. Arthritis research & therapy 17:241. doi: 10.1186/s13075-015-0750-y CrossRefGoogle Scholar
  67. 67.
    Nocturne G, Cornec D, Seror R, Mariette X (2015) New biological therapies in Sjogren’s syndrome. Best Pract Res Clin Rheumatol 29(6):783–793. doi: 10.1016/j.berh.2016.02.009 CrossRefPubMedGoogle Scholar
  68. 68.
    Brown S, Navarro Coy N, Pitzalis C, Emery P, Pavitt S, Gray J, Hulme C, Hall F, Busch R, Smith P, Dawson L, Bombardieri M, Wan-Fai N, Pease C, Price E, Sutcliffe N, Woods C, Ruddock S, Everett C, Reynolds C, Skinner E, Poveda-Gallego A, Rout J, Macleod I, Rauz S, Bowman S, team Tt (2014) The TRACTISS protocol: a randomised double blind placebo controlled clinical trial of anti-B-cell therapy in patients with primary Sjogren’s syndrome. BMC Musculoskelet Disord 15:21. doi: 10.1186/1471-2474-15-21 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Meijer JM, Meiners PM, Vissink A, Spijkervet FK, Abdulahad W, Kamminga N, Brouwer E, Kallenberg CG, Bootsma H (2010) Effectiveness of rituximab treatment in primary Sjogren’s syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis & Rheumatism 62(4):960–968. doi: 10.1002/art.27314 CrossRefGoogle Scholar
  70. 70.
    Jousse-Joulin S, Devauchelle-Pensec V, Cornec D, Marhadour T, Bressollette L, Gestin S, Pers JO, Nowak E, Saraux A (2015) Brief report: ultrasonographic assessment of salivary gland response to rituximab in primary Sjogren’s syndrome. Arthritis & Rheumatology 67(6):1623–1628. doi: 10.1002/art.39088 CrossRefGoogle Scholar
  71. 71.
    Delli K, Haacke EA, Kroese FG, Pollard RP, Ihrler S, van der Vegt B, Vissink A, Bootsma H, Spijkervet FK (2016) In primary Sjogren’s syndrome high absolute numbers and proportions of B cells in parotid glands predict responsiveness to rituximab as defined by ESSDAI, but not by SSRI. Ann Rheum Dis 75(6):e34. doi: 10.1136/annrheumdis-2016-209317 CrossRefPubMedGoogle Scholar
  72. 72.
    Cornec D, Costa S, Devauchelle-Pensec V, Chiche L, Saraux A, Pers JO (2016) Do high numbers of salivary gland-infiltrating B cells predict better or worse outcomes after rituximab in patients with primary Sjogren’s syndrome? Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-209300
  73. 73.
    Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, Desmoulins F, Nocturne G, Ravaud P, De Vita S (2015) Efficacy and safety of belimumab in primary Sjogren’s syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis 74(3):526–531. doi: 10.1136/annrheumdis-2013-203991 CrossRefPubMedGoogle Scholar
  74. 74.
    Finak G, Langweiler M, Jaimes M, Malek M, Taghiyar J, Korin Y, Raddassi K, Devine L, Obermoser G, Pekalski ML, Pontikos N, Diaz A, Heck S, Villanova F, Terrazzini N, Kern F, Qian Y, Stanton R, Wang K, Brandes A, Ramey J, Aghaeepour N, Mosmann T, Scheuermann RH, Reed E, Palucka K, Pascual V, Blomberg BB, Nestle F, Nussenblatt RB, Brinkman RR, Gottardo R, Maecker H, McCoy JP (2016) Standardizing flow cytometry immunophenotyping analysis from the Human ImmunoPhenotyping Consortium. Scientific reports 6:20686. doi: 10.1038/srep20686 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    McNeil LK, Price L, Britten CM, Jaimes M, Maecker H, Odunsi K, Matsuzaki J, Staats JS, Thorpe J, Yuan J, Janetzki S (2013) A harmonized approach to intracellular cytokine staining gating: results from an international multiconsortia proficiency panel conducted by the Cancer Immunotherapy Consortium (CIC/CRI). Cytometry A 83(8):728–738. doi: 10.1002/cyto.a.22319 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Jamin C, Le Lann L, Alvarez-Errico D, Barbarroja N, Cantaert T, Ducreux J, Dufour AM, Gerl V, Kniesch K, Neves E, Trombetta E, Alarcon-Riquelme M, Maranon C, Pers JO (2016) Multi-center harmonization of flow cytometers in the context of the European “PRECISESADS” project. Autoimmun Rev 15(11):1038–1045. doi: 10.1016/j.autrev.2016.07.034 CrossRefPubMedGoogle Scholar
  77. 77.
    Daien CI, Morel J (2014) Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine. Mediat Inflamm 2014:386148. doi: 10.1155/2014/386148 CrossRefGoogle Scholar
  78. 78.
    Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L, Dijkmans BA, Tak PP, Wolbink GJ (2007) Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 66(7):921–926. doi: 10.1136/ard.2006.065615 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Rojas-Serrano J, Perez LL, Garcia CG, Moctezuma F, Alvarez-Hernandez E, Vazquez-Mellado J, Montiel JL, Burgos-Vargas R (2011) Current smoking status is associated to a non-ACR 50 response in early rheumatoid arthritis. A cohort study. Clin Rheumatol 30(12):1589–1593. doi: 10.1007/s10067-011-1775-5 CrossRefPubMedGoogle Scholar
  80. 80.
    Saevarsdottir S, Wedren S, Seddighzadeh M, Bengtsson C, Wesley A, Lindblad S, Askling J, Alfredsson L, Klareskog L (2011) Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis & Rheumatism 63(1):26–36. doi: 10.1002/art.27758 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kristina Schreiber
    • 1
  • Gaetane Nocturne
    • 2
  • Divi Cornec
    • 3
  • Claire I. Daïen
    • 1
    • 4
  1. 1.Rheumatology DepartmentLapeyronie Hospital and Montpellier I UniversityMontpellierFrance
  2. 2.Rheumatology DepartmentParisFrance
  3. 3.Rheumatology DepartmentBrestFrance
  4. 4.Institute of Molecular GeneticUMR 5535, CNRSMontpellierFrance

Personalised recommendations