Peripheral blood regulatory T cells and disease activity, quality of life, and outcomes in children with juvenile idiopathic arthritis.
Juvenile idiopathic arthritis
Patient-reported outcomes
T regulatory cells
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
received:
13
05
2024
accepted:
20
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
1
8
2024
Statut:
epublish
Résumé
To measure regulatory T cell (Treg) levels in the peripheral blood of children with juvenile idiopathic arthritis (JIA) and analyse the association of this measure with disease activity, quality of life, adjustment of treatment, and hospitalisation. We conducted a two-phase study (cross-sectional and prospective), including consecutive children with a JIA diagnosis according to ILAR criteria. Our independent variables were Tregs, Th1, Th2, and cytokines in peripheral blood, and our dependent variables in the cross-sectional phase were arthritis category, JIA activity, and patient-reported outcomes. To test associations, we used Spearman's correlation coefficient and the Mann-Whitney U test. In the prospective phase, we explored the probability of treatment adjustment and hospitalisation for JIA during follow-up according to Tregs levels at baseline, using Cox proportional regression. Our sample included 87 participants (median age 11 years, 63.2% girls). Tregs were not associated with most variables of interest. However, we found that higher Tregs concentration was associated with lower erythrocyte sedimentation rate (ESR) and better subjective disease status and course, while higher IL-10 and TGF-β levels were associated with lower ESR, less pain, and better subjective disease status We found no association between Tregs and treatment adjustments or hospitalisation. Higher baseline Treg levels in the peripheral blood of children with JIA may be associated with reduced disease activity and better quality of life, though were not informative on the inflammatory progression on the follow-up.
Identifiants
pubmed: 39090751
doi: 10.1186/s12969-024-01006-x
pii: 10.1186/s12969-024-01006-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
69Subventions
Organisme : ISABIAL
ID : VIII Convocatoria de Ayudas para el Apoyo y Fomento de la Investigación de ISABIAL, EXP.2021-0443
Organisme : Sociedad Valenciana Reumatologia
ID : Beca de Investigación de la Fundación Valenciana de Reumatología, 2019
Informations de copyright
© 2024. The Author(s).
Références
Thierry S, Fautrel B, Lemelle I, Guillemin F. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Joint Bone Spine. 2014;81:112–7. https://doi.org/10.1016/j.jbspin.2013.09.003 .
doi: 10.1016/j.jbspin.2013.09.003
pubmed: 24210707
Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur A-M, Suarez-Almazor ME, Woo P. International League of Associations for Rheumatology, International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.
pubmed: 14760812
Eng SWM, Duong TT, Rosenberg AM, Morris Q, Yeung RSM. REACCH OUT and BBOP Research Consortia, the biologic basis of clinical heterogeneity in juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66:3463–75. https://doi.org/10.1002/art.38875 .
doi: 10.1002/art.38875
pubmed: 25200124
pmcid: 4282094
Rezaei E, Hogan D, Trost B, Kusalik AJ, Boire G, Cabral DA, Campillo S, Chédeville G, Chetaille A-L, Dancey P, Duffy C, Duffy KW, Eng SWM, Gordon J, Guzman J, Houghton K, Huber AM, Jurencak R, Lang B, Laxer RM, Morishita K, Oen KG, Petty RE, Ramsey SE, Scherer SW, Scuccimarri R, Spiegel L, Stringer E, Taylor-Gjevre RM, Tse SML, Tucker LB, Turvey SE, Tupper S, Wintle RF, Yeung RSM, Rosenberg AM. BBOP Study Group, associations of clinical and inflammatory biomarker clusters with juvenile idiopathic arthritis categories. Rheumatology (Oxford). 2020;59:1066–75. https://doi.org/10.1093/rheumatology/kez382 .
doi: 10.1093/rheumatology/kez382
pubmed: 32321162
Martini A, Ravelli A, Avcin T, Beresford MW, Burgos-Vargas R, Cuttica R, Ilowite NT, Khubchandani R, Laxer RM, Lovell DJ, Petty RE, Wallace CA, Wulffraat NM, Pistorio A, Ruperto N. Pediatric Rheumatology International Trials Organization (PRINTO), toward new classification criteria for juvenile idiopathic arthritis: first steps. Pediatr Rheumatol Int Trials Organ Int Consensus J Rheumatol. 2019;46:190–7. https://doi.org/10.3899/jrheum.180168 .
doi: 10.3899/jrheum.180168
Ravelli A, Consolaro A, Horneff G, Laxer RM, Lovell DJ, Wulffraat NM, Akikusa JD, Al-Mayouf SM, Antón J, Avcin T, Berard RA, Beresford MW, Burgos-Vargas R, Cimaz R, De Benedetti F, Demirkaya E, Foell D, Itoh Y, Lahdenne P, Morgan EM, Quartier P, Ruperto N, Russo R, Saad-Magalhães C, Sawhney S, Scott C, Shenoi S, Swart JF, Uziel Y, Vastert SJ, Smolen JS. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2018;77:819–28. https://doi.org/10.1136/annrheumdis-2018-213030 .
doi: 10.1136/annrheumdis-2018-213030
pubmed: 29643108
Giancane G, Muratore V, Marzetti V, Quilis N, Benavente BS, Bagnasco F, Alongi A, Civino A, Quartulli L, Consolaro A, Ravelli A. Disease activity and damage in juvenile idiopathic arthritis: methotrexate era versus biologic era. Arthritis Res Ther. 2019;21:168. https://doi.org/10.1186/s13075-019-1950-7 .
doi: 10.1186/s13075-019-1950-7
pubmed: 31287015
pmcid: 6615271
Shoop-Worrall SJW, Kearsley-Fleet L, Thomson W, Verstappen SMM, Hyrich KL. How common is remission in juvenile idiopathic arthritis: a systematic review. Semin Arthritis Rheum. 2017;47:331–7. https://doi.org/10.1016/j.semarthrit.2017.05.007 .
doi: 10.1016/j.semarthrit.2017.05.007
pubmed: 28625712
pmcid: 5687936
Wallace CA, Ruperto N, Giannini E. Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology International Trials Organization, Pediatric Rheumatology Collaborative Study Group, preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004;31:2290–4.
pubmed: 15517647
Consolaro A, Bracciolini G, Ruperto N, Pistorio A, Magni-Manzoni S, Malattia C, Pederzoli S, Davì S, Martini A, Ravelli A. Paediatric Rheumatology International Trials Organization, Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: defining criteria based on the juvenile arthritis disease activity score. Arthritis Rheum. 2012;64:2366–74. https://doi.org/10.1002/art.34373 .
doi: 10.1002/art.34373
pubmed: 22231288
Consolaro A, Negro G, Chiara Gallo M, Bracciolini G, Ferrari C, Schiappapietra B, Pistorio A, Bovis F, Ruperto N, Martini A, Ravelli A. Defining criteria for disease activity states in nonsystemic juvenile idiopathic arthritis based on a three-variable juvenile arthritis disease activity score. Arthritis Care Res (Hoboken). 2014;66:1703–9. https://doi.org/10.1002/acr.22393 .
doi: 10.1002/acr.22393
pubmed: 24980508
Ravelli A, Martini A. Remission in juvenile idiopathic arthritis. Clin Exp Rheumatol 24 (2006) S105–110.
Shenoi S, Wallace CA. Remission in juvenile idiopathic arthritis: current facts. Curr Rheumatol Rep. 2010;12:80–6. https://doi.org/10.1007/s11926-010-0085-2 .
doi: 10.1007/s11926-010-0085-2
pubmed: 20425015
Rypdal V, Arnstad ED, Aalto K, Berntson L, Ekelund M, Fasth A, Glerup M, Herlin T, Nielsen S, Peltoniemi S, Zak M, Rygg M, Rypdal M, Nordal E. Nordic Study Group of Pediatric Rheumatology (NoSPeR), Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the nordic cohort study. Arthritis Res Ther. 2018;20:91. https://doi.org/10.1186/s13075-018-1571-6 .
doi: 10.1186/s13075-018-1571-6
pubmed: 29724248
pmcid: 5934822
Guzman J, Henrey A, Loughin T, Berard RA, Shiff NJ, Jurencak R, Huber AM, Oen K, Gerhold K, Feldman BM, Scuccimarri R, Houghton K, Chédeville G, Morishita K, Lang B, Dancey P, Rosenberg AM, Barsalou J, Bruns A, Watanabe Duffy K, Benseler S, Duffy CM, Tucker LB. ReACCh-Out investigators, Predicting which children with juvenile idiopathic arthritis will not attain early remission with Conventional Treatment: results from the ReACCh-Out cohort. J Rheumatol. 2019;46:628–35. https://doi.org/10.3899/jrheum.180456 .
doi: 10.3899/jrheum.180456
pubmed: 30647178
Spreafico R, Rossetti M, van Loosdregt J, Wallace CA, Massa M, Magni-Manzoni S, Gattorno M, Martini A, Lovell DJ, Albani S. A circulating reservoir of pathogenic-like CD4 + T cells shares a genetic and phenotypic signature with the inflamed synovial micro-environment. Ann Rheum Dis. 2016;75:459–65. https://doi.org/10.1136/annrheumdis-2014-206226 .
doi: 10.1136/annrheumdis-2014-206226
pubmed: 25498120
Rossetti M, Spreafico R, Consolaro A, Leong JY, Chua C, Massa M, Saidin S, Magni-Manzoni S, Arkachaisri T, Wallace CA, Gattorno M, Martini A, Lovell DJ, Albani S. TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis. Ann Rheum Dis. 2017;76:435–41. https://doi.org/10.1136/annrheumdis-2015-208992 .
doi: 10.1136/annrheumdis-2015-208992
pubmed: 27311837
van Dijkhuizen EHP, Del Chierico F, Malattia C, Russo A, Pires Marafon D, Ter Haar NM, Magni-Manzoni S, Vastert SJ, Dallapiccola B, Prakken B, Martini A, De Benedetti F, Putignani L, Model Driven Paediatric European Digital Repository Consortium. Microbiome Analytics of the gut microbiota in patients with juvenile idiopathic arthritis: a longitudinal Observational Cohort Study. Arthritis Rheumatol. 2019;71:1000–10. https://doi.org/10.1002/art.40827 .
doi: 10.1002/art.40827
pubmed: 30592383
pmcid: 6593809
Orczyk K, Smolewska E. The potential importance of MicroRNAs as Novel indicators how to manage patients with juvenile idiopathic arthritis more effectively. J Immunol Res. 2021;2021:9473508. https://doi.org/10.1155/2021/9473508 .
doi: 10.1155/2021/9473508
pubmed: 33575364
pmcid: 7864733
Rosina S, Natoli V, Santaniello S, Trincianti C, Consolaro A, Ravelli A. Novel biomarkers for prediction of outcome and therapeutic response in juvenile idiopathic arthritis. Expert Rev Clin Immunol. 2021;17:853–70. https://doi.org/10.1080/1744666X.2021.1945441 .
doi: 10.1080/1744666X.2021.1945441
pubmed: 34139935
Fischer J, Dirks J, Haase G, Holl-Wieden A, Hofmann C, Girschick H, Morbach H. IL-21 + CD4 + T helper cells co-expressing IFN-γ and TNF-α accumulate in the joints of antinuclear antibody positive patients with juvenile idiopathic arthritis. Clin Immunol. 2020;217:108484. https://doi.org/10.1016/j.clim.2020.108484 .
doi: 10.1016/j.clim.2020.108484
pubmed: 32485239
Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3 + regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10:490–500. https://doi.org/10.1038/nri2785 .
doi: 10.1038/nri2785
pubmed: 20559327
Shan J, Jin H, Xu Y, Cell Metabolism T. A New Perspective on Th17/Treg Cell Imbalance in systemic Lupus Erythematosus. Front Immunol. 2020;11:1027. https://doi.org/10.3389/fimmu.2020.01027 .
doi: 10.3389/fimmu.2020.01027
pubmed: 32528480
pmcid: 7257669
Jiang Q, Yang G, Liu Q, Wang S, Cui D. Function and Role of Regulatory T Cells in rheumatoid arthritis. Front Immunol. 2021;12:626193. https://doi.org/10.3389/fimmu.2021.626193 .
doi: 10.3389/fimmu.2021.626193
pubmed: 33868244
pmcid: 8047316
Feng M, Guo H, Zhang C, Wang Y, Liang Z, Zhao X, Qin Y, Wu Y, Liu G, Gao C, Luo J. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019;77:105912. https://doi.org/10.1016/j.intimp.2019.105912 .
doi: 10.1016/j.intimp.2019.105912
pubmed: 31669890
Frantz C, Auffray C, Avouac J, Allanore Y. Regulatory T cells in systemic sclerosis. Front Immunol. 2018;9:2356. https://doi.org/10.3389/fimmu.2018.02356 .
doi: 10.3389/fimmu.2018.02356
pubmed: 30374354
pmcid: 6196252
Stelmaszczyk-Emmel A, Jackowska T, Rutkowska-Sak L, Marusak-Banacka M, Wąsik M. Identification, frequency, activation and function of CD4 + CD25(high)FoxP3 + regulatory T cells in children with juvenile idiopathic arthritis. Rheumatol Int. 2012;32:1147–54. https://doi.org/10.1007/s00296-010-1728-3 .
doi: 10.1007/s00296-010-1728-3
pubmed: 21249500
Haufe S, Haug M, Schepp C, Kuemmerle-Deschner J, Hansmann S, Rieber N, Tzaribachev N, Hospach T, Maier J, Dannecker GE, Holzer U. Impaired suppression of synovial fluid CD4 + CD25- T cells from patients with juvenile idiopathic arthritis by CD4 + CD25 + Treg cells. Arthritis Rheum. 2011;63:3153–62. https://doi.org/10.1002/art.30503 .
doi: 10.1002/art.30503
pubmed: 21702013
Bending D, Giannakopoulou E, Lom H, Wedderburn LR. Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and require local signals to stabilize FOXP3 protein expression. J Immunol. 2015;195:5616–24. https://doi.org/10.4049/jimmunol.1500391 .
doi: 10.4049/jimmunol.1500391
pubmed: 26561546
pmcid: 4671090
Henderson LA, Volpi S, Frugoni F, Janssen E, Kim S, Sundel RP, Dedeoglu F, Lo MS, Hazen MM, Beth Son M, Mathieu R, Zurakowski D, Yu N, Lebedeva T, Fuhlbrigge RC, Walter JE, Nee Lee Y, Nigrovic PA, Notarangelo LD. Next-generation sequencing reveals restriction and clonotypic expansion of Treg Cells in Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2016;68:1758–68. https://doi.org/10.1002/art.39606 .
doi: 10.1002/art.39606
pubmed: 26815131
pmcid: 5398095
Juanola O, Moratalla A, Gutiérrez A, Sempere L, Zapater P, Giménez P, Almenta I, Peiró G, González-Navajas JM, Such JF, Francés R. Anti-TNF-alpha loss of response is associated with a decreased percentage of FoxP3 + T cells and a variant NOD2 genotype in patients with Crohn’s disease. J Gastroenterol. 2015;50:758–68. https://doi.org/10.1007/s00535-014-1020-5 .
doi: 10.1007/s00535-014-1020-5
pubmed: 25500977
Nordal EB, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, Lahdenne P, Nielsen S, Peltoniemi S, Straume B, Rygg M. Validity and predictive ability of the juvenile arthritis disease activity score based on CRP versus ESR in a nordic population-based setting. Ann Rheum Dis. 2012;71:1122–7. https://doi.org/10.1136/annrheumdis-2011-200237 .
doi: 10.1136/annrheumdis-2011-200237
pubmed: 22258487
McErlane F, Beresford MW, Baildam EM, Chieng SEA, Davidson JE, Foster HE, Gardner-Medwin J, Lunt M, Wedderburn LR, Thomson W, Hyrich KL. Childhood arthritis prospective study (CAPS), validity of a three-variable Juvenile Arthritis Disease Activity score in children with new-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2013;72:1983–8. https://doi.org/10.1136/annrheumdis-2012-202031 .
doi: 10.1136/annrheumdis-2012-202031
pubmed: 23256951
Filocamo G, Consolaro A, Schiappapietra B, Dalprà S, Lattanzi B, Magni-Manzoni S, Ruperto N, Pistorio A, Pederzoli S, Civino A, Guseinova D, Masala E, Viola S, Martini A, Ravelli A. A new approach to clinical care of juvenile idiopathic arthritis: the Juvenile Arthritis Multidimensional Assessment Report. J Rheumatol. 2011;38:938–53. https://doi.org/10.3899/jrheum.100930 .
doi: 10.3899/jrheum.100930
pubmed: 21362761
Schober P, Boer C, Schwarte LA. Correlation coefficients: appropriate use and interpretation. Anesth Analgesia. 2018;126:1763. https://doi.org/10.1213/ANE.0000000000002864 .
doi: 10.1213/ANE.0000000000002864
Bending D, Pesenacker AM, Ursu S, Wu Q, Lom H, Thirugnanabalan B, Wedderburn LR. Hypomethylation at the Regulatory T cell–specific Demethylated Region in CD25hi T cells is decoupled from FOXP3 expression at the Inflamed Site in Childhood Arthritis. J Immunol. 2014;193:2699–708. https://doi.org/10.4049/jimmunol.1400599 .
doi: 10.4049/jimmunol.1400599
pubmed: 25092890
pmcid: 4157061
de Kleer IM, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M, de Jager W, Pugayung G, Giannoni F, Rijkers G, Albani S, Kuis W, Prakken B. CD4 + CD25bright Regulatory T cells actively regulate inflammation in the joints of patients with the Remitting form of Juvenile Idiopathic Arthritis. J Immunol. 2004;172:6435–43. https://doi.org/10.4049/jimmunol.172.10.6435 .
doi: 10.4049/jimmunol.172.10.6435
pubmed: 15128835
Grose RH, Millard DJ, Mavrangelos C, Barry SC, Zola H, Nicholson IC, Cham WT, Boros CA, Krumbiegel D. Comparison of blood and synovial fluid th17 and novel peptidase inhibitor 16 Treg cell subsets in juvenile idiopathic arthritis. J Rheumatol. 2012;39:2021–31. https://doi.org/10.3899/jrheum.111421 .
doi: 10.3899/jrheum.111421
pubmed: 22896021
Luca N, Feldman BM. Pediatric rheumatology: improving the assessment of children with JIA. Nat Rev Rheumatol. 2011;7:442–4. https://doi.org/10.1038/nrrheum.2011.99 .
doi: 10.1038/nrrheum.2011.99
pubmed: 21727934
Berard R, Laxer RM. Improving the quality of care in children with juvenile idiopathic arthritis: a step in the right direction. J Rheumatol. 2011;38:789–90. https://doi.org/10.3899/jrheum.110047 .
doi: 10.3899/jrheum.110047
pubmed: 21532058
Chen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, Voehringer D, Schett G, Bozec A. Th2 and eosinophil responses suppress inflammatory arthritis. Nat Commun. 2016;7:11596. https://doi.org/10.1038/ncomms11596 .
doi: 10.1038/ncomms11596
pubmed: 27273006
pmcid: 4899615
Stockis J, Colau D, Coulie PG, Lucas S. Membrane protein GARP is a receptor for latent TGF-β on the surface of activated human Treg. Eur J Immunol. 2009;39:3315–22. https://doi.org/10.1002/eji.200939684 .
doi: 10.1002/eji.200939684
pubmed: 19750484
Pesenacker AM, Wedderburn LR. T regulatory cells in childhood arthritis–novel insights. Expert Rev Mol Med. 2013;15:e13. https://doi.org/10.1017/erm.2013.14 .
doi: 10.1017/erm.2013.14
pubmed: 24294966