Thymic function in juvenile idiopathic arthritis

A. R. Lorenzi, T. A. Morgan, A. Anderson, J. Catterall, Angela Margaret Patterson, H. E. Foster, J. D. Isaacs

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.

Methods: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alpha TREC/Sigma beta TREC ratio. Lastly, regulatory T cells (T-Reg) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.

Results: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.

Conclusions: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA'' suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

Original languageEnglish
Pages (from-to)983-990
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume68
Issue number6
Early online date15 Jul 2008
DOIs
Publication statusPublished - Jun 2009

Keywords

  • STEM-CELL TRANSPLANTATION
  • BONE-MARROW-TRANSPLANTATION
  • REGULATORY T-CELLS
  • RHEUMATOID-ARTHRITIS
  • PERIPHERAL-BLOOD
  • MULTIPLE-SCLEROSIS
  • HIV-INFECTION
  • NAIVE
  • RECONSTITUTION
  • REPERTOIRE

Cite this

Lorenzi, A. R., Morgan, T. A., Anderson, A., Catterall, J., Patterson, A. M., Foster, H. E., & Isaacs, J. D. (2009). Thymic function in juvenile idiopathic arthritis. Annals of the Rheumatic Diseases, 68(6), 983-990. https://doi.org/10.1136/ard.2008.088112

Thymic function in juvenile idiopathic arthritis. / Lorenzi, A. R.; Morgan, T. A.; Anderson, A.; Catterall, J.; Patterson, Angela Margaret; Foster, H. E.; Isaacs, J. D.

In: Annals of the Rheumatic Diseases, Vol. 68, No. 6, 06.2009, p. 983-990.

Research output: Contribution to journalArticle

Lorenzi, AR, Morgan, TA, Anderson, A, Catterall, J, Patterson, AM, Foster, HE & Isaacs, JD 2009, 'Thymic function in juvenile idiopathic arthritis', Annals of the Rheumatic Diseases, vol. 68, no. 6, pp. 983-990. https://doi.org/10.1136/ard.2008.088112
Lorenzi AR, Morgan TA, Anderson A, Catterall J, Patterson AM, Foster HE et al. Thymic function in juvenile idiopathic arthritis. Annals of the Rheumatic Diseases. 2009 Jun;68(6):983-990. https://doi.org/10.1136/ard.2008.088112
Lorenzi, A. R. ; Morgan, T. A. ; Anderson, A. ; Catterall, J. ; Patterson, Angela Margaret ; Foster, H. E. ; Isaacs, J. D. / Thymic function in juvenile idiopathic arthritis. In: Annals of the Rheumatic Diseases. 2009 ; Vol. 68, No. 6. pp. 983-990.
@article{b2038cab3ed7456ab06999ea64a8ad2b,
title = "Thymic function in juvenile idiopathic arthritis",
abstract = "Objective: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.Methods: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; {\%}RTEs) were quantified and intrathymic proliferation measured by calculating the alpha TREC/Sigma beta TREC ratio. Lastly, regulatory T cells (T-Reg) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.Results: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.Conclusions: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term {"}JIA'' suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.",
keywords = "STEM-CELL TRANSPLANTATION, BONE-MARROW-TRANSPLANTATION, REGULATORY T-CELLS, RHEUMATOID-ARTHRITIS, PERIPHERAL-BLOOD, MULTIPLE-SCLEROSIS, HIV-INFECTION, NAIVE, RECONSTITUTION, REPERTOIRE",
author = "Lorenzi, {A. R.} and Morgan, {T. A.} and A. Anderson and J. Catterall and Patterson, {Angela Margaret} and Foster, {H. E.} and Isaacs, {J. D.}",
year = "2009",
month = "6",
doi = "10.1136/ard.2008.088112",
language = "English",
volume = "68",
pages = "983--990",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "6",

}

TY - JOUR

T1 - Thymic function in juvenile idiopathic arthritis

AU - Lorenzi, A. R.

AU - Morgan, T. A.

AU - Anderson, A.

AU - Catterall, J.

AU - Patterson, Angela Margaret

AU - Foster, H. E.

AU - Isaacs, J. D.

PY - 2009/6

Y1 - 2009/6

N2 - Objective: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.Methods: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alpha TREC/Sigma beta TREC ratio. Lastly, regulatory T cells (T-Reg) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.Results: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.Conclusions: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA'' suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

AB - Objective: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined.Methods: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alpha TREC/Sigma beta TREC ratio. Lastly, regulatory T cells (T-Reg) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset.Results: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD.Conclusions: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA'' suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

KW - STEM-CELL TRANSPLANTATION

KW - BONE-MARROW-TRANSPLANTATION

KW - REGULATORY T-CELLS

KW - RHEUMATOID-ARTHRITIS

KW - PERIPHERAL-BLOOD

KW - MULTIPLE-SCLEROSIS

KW - HIV-INFECTION

KW - NAIVE

KW - RECONSTITUTION

KW - REPERTOIRE

U2 - 10.1136/ard.2008.088112

DO - 10.1136/ard.2008.088112

M3 - Article

VL - 68

SP - 983

EP - 990

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 6

ER -