Abstract
OBJECTIVES—The aim of this study was to evaluate serum interleukin (IL) 12 concentration in patients with juvenile chronic arthritis (JCA), according to disease subtype, activity, and duration. IL12 has been demonstrated to prime the selective expansion of T helper (Th) cells with a Th1-type pattern of cytokine production. METHODS—Sixty eight serum samples from 50 JCA patients (12 systemic, 12 polyarticular, 26 pauciarticular), 20 serum samples from age matched healthy controls were tested with two different immunoassays specific for total IL12 (p40 and p70 heterodimer) and for IL12 (p70) heterodimer, respectively. The following disease activity parameters were evaluated: (a) presence of arthritis at least in one joint, (b) physician global estimate of disease activity, (c) disability index according to the Childhood Health Assessment Questionnaire (CHAQ), (d) C reactive protein (CRP). RESULTS—Total IL12 (p40 and p70 heterodimer) was significantly higher in JCA active patients than in those on clinical remission and in healthy controls (p < 0.001). Conversely, detectable concentrations of IL12 (p70) heterodimer were found in three active JCA patients only. Moreover, total IL12 (p40 and p70 heterodimer) showed a significant negative correlation both with time from disease diagnosis (r = −0.29, p = 0.04) and, for the pauciarticular subgroup, with disease activity duration (r = − 0.71, p < 0.001). CONCLUSIONS—This study shows that the p40 moiety of IL12 is increased in serum samples from active JCA patients, especially in the earliest phases of the disease, whereas biological active IL12 (p70) heterodimer is virtually undetectable. Keywords: juvenile chronic arthritis; interluekin 12; cytokines; T helper cells
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Figure 1 .
Difference in IL12 (p40) serum concentration among systemic, polyarticular, and pauciarticular JCA patients with active and inactive disease and age matched healthy controls. The horizontal lines represent the mean values detected in each study group.
Figure 2 .
Cross sectional study of IL12 (p40) serum concentrations in active pauciarticular JCA patients according to duration of disease activity. Cut off value was 145 pg/ml (hatched area). Data were fitted by a two phase exponential decrease curve (r2 = 0.77).
Selected References
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- Abbas A. K., Murphy K. M., Sher A. Functional diversity of helper T lymphocytes. Nature. 1996 Oct 31;383(6603):787–793. doi: 10.1038/383787a0. [DOI] [PubMed] [Google Scholar]
- Bucht A., Larsson P., Weisbrot L., Thorne C., Pisa P., Smedegård G., Keystone E. C., Grönberg A. Expression of interferon-gamma (IFN-gamma), IL-10, IL-12 and transforming growth factor-beta (TGF-beta) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA). Clin Exp Immunol. 1996 Mar;103(3):357–367. doi: 10.1111/j.1365-2249.1996.tb08288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cope A. P., Aderka D., Doherty M., Engelmann H., Gibbons D., Jones A. C., Brennan F. M., Maini R. N., Wallach D., Feldmann M. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum. 1992 Oct;35(10):1160–1169. doi: 10.1002/art.1780351008. [DOI] [PubMed] [Google Scholar]
- Del Prete G. F., De Carli M., Mastromauro C., Biagiotti R., Macchia D., Falagiani P., Ricci M., Romagnani S. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest. 1991 Jul;88(1):346–350. doi: 10.1172/JCI115300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Prete G., Maggi E., Parronchi P., Chrétien I., Tiri A., Macchia D., Ricci M., Banchereau J., De Vries J., Romagnani S. IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol. 1988 Jun 15;140(12):4193–4198. [PubMed] [Google Scholar]
- Dolhain R. J., van der Heiden A. N., ter Haar N. T., Breedveld F. C., Miltenburg A. M. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum. 1996 Dec;39(12):1961–1969. doi: 10.1002/art.1780391204. [DOI] [PubMed] [Google Scholar]
- Fantini F., Corvaglia G., Bergomi P., Gattinara M., Gerloni V., Lomater C., Mazzotti J., Calori G., Galli L. Validation of the Italian version of the Stanford Childhood Health Assessment Questionnaire for measuring functional status in children with chronic arthritis. Clin Exp Rheumatol. 1995 Nov-Dec;13(6):785–791. [PubMed] [Google Scholar]
- Gattorno M., Facchetti P., Ghiotto F., Vignola S., Buoncompagni A., Prigione I., Picco P., Pistoia V. Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype. Clin Exp Immunol. 1997 Jul;109(1):4–11. doi: 10.1046/j.1365-2249.1997.4331330.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gattorno M., Picco P., Buoncompagni A., Stalla F., Facchetti P., Sormani M. P., Pistoia V. Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity in juvenile chronic arthritis. Ann Rheum Dis. 1996 Apr;55(4):243–247. doi: 10.1136/ard.55.4.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haanen J. B., de Waal Malefijt R., Res P. C., Kraakman E. M., Ottenhoff T. H., de Vries R. R., Spits H. Selection of a human T helper type 1-like T cell subset by mycobacteria. J Exp Med. 1991 Sep 1;174(3):583–592. doi: 10.1084/jem.174.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manetti R., Gerosa F., Giudizi M. G., Biagiotti R., Parronchi P., Piccinni M. P., Sampognaro S., Maggi E., Romagnani S., Trinchieri G. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med. 1994 Apr 1;179(4):1273–1283. doi: 10.1084/jem.179.4.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manetti R., Gerosa F., Giudizi M. G., Biagiotti R., Parronchi P., Piccinni M. P., Sampognaro S., Maggi E., Romagnani S., Trinchieri G. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med. 1994 Apr 1;179(4):1273–1283. doi: 10.1084/jem.179.4.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manetti R., Parronchi P., Giudizi M. G., Piccinni M. P., Maggi E., Trinchieri G., Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 1993 Apr 1;177(4):1199–1204. doi: 10.1084/jem.177.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McIntyre K. W., Shuster D. J., Gillooly K. M., Warrier R. R., Connaughton S. E., Hall L. B., Arp L. H., Gately M. K., Magram J. Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice. Eur J Immunol. 1996 Dec;26(12):2933–2938. doi: 10.1002/eji.1830261219. [DOI] [PubMed] [Google Scholar]
- Panayi G. S., Lanchbury J. S., Kingsley G. H. The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum. 1992 Jul;35(7):729–735. doi: 10.1002/art.1780350702. [DOI] [PubMed] [Google Scholar]
- Ravelli A., Viola S., Ruperto N., Corsi B., Ballardini G., Martini A. Correlation between conventional disease activity measures in juvenile chronic arthritis. Ann Rheum Dis. 1997 Mar;56(3):197–200. doi: 10.1136/ard.56.3.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. doi: 10.1126/science.254.5029.279. [DOI] [PubMed] [Google Scholar]
- Simon A. K., Seipelt E., Sieper J. Divergent T-cell cytokine patterns in inflammatory arthritis. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8562–8566. doi: 10.1073/pnas.91.18.8562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trembleau S., Penna G., Bosi E., Mortara A., Gately M. K., Adorini L. Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice. J Exp Med. 1995 Feb 1;181(2):817–821. doi: 10.1084/jem.181.2.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trinchieri G. Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood. 1994 Dec 15;84(12):4008–4027. [PubMed] [Google Scholar]