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The Variation Of Th1/Th2 Cell Balance Of Peripheral Blood From Patients With Juvenile Rheumatoid Arthritis

Posted on:2006-04-11Degree:MasterType:Thesis
Country:ChinaCandidate:J GuoFull Text:PDF
GTID:2144360155952499Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Juvenile rheumatoid arthritis (JRA) is a kind of disease characteristic of chronic arthritis which children under 16 years old often suffered from. General pathological change JRA is chronic inflammation of synovium of joint and conjunction organization. If the arthritis lasts too time, arthrodial cartilage or the tissues under gristle will be damaged, even led to permanence artic crippledom at the end. At present, it is a general view that JRA is a systemic and heterogeneity autoimmune disease. With the development of immunology and more studies on the subgroup of T cell, especially on CD+4 T Th1/Th2,it was found that the balance of Thl and Th2 was an important element in immune response regulation. Helper T cells are consisted of Thl cell and Th2 cell. Th1 cell and Th2 cell could be transformed into each other. In normal state, they are in balance but when they were off balance, the immune system will be disturbed that the Th1 cell or Th2 cell will get advantage over the other, this is called Thl drift or Th2 drift. In general, when the Th1 cell and the cytokines they excrete are dominant, it is called Th1 cell predominance, and the other state is called Th2 predominance. One predominance could inhibit the other one. The more understanding of the helper T cell Th1/Th2, the more understanding of the network of cytokines. Now, it is known that the balance of Thl cell and Th2 cell is the most important element in the cytokines network balance. IFN-γand IL-4 reflect the level of Th1 and Th2, respectively, and, it is always to use the rate of IFN-γ/IL-4 to reflect the level of Th1 and Th2 in immunology. JRA is a systemic autoimmune disease that the homeostatic function of T cell is damaged. In JRA patients, the peripheral tolerance mechanism is confused, T cell proliferation function will be abnormal, the amount of potentiality autoreactivity T cells will be increased. Cells competition will inhibit the proliferation of other normal T cells. RA is classified into the disease that the function of Th1/Th2 is abnormal and the activities of Th1 cell get advantages over Th2 cell. In our country, most of the studies on the relationship between Th1/Th2 and RA focus on mature, there are few reports about JRA, since JRA is a disease which children often suffer from, the onset rate of JRA is about 5% of the total ofrheumatoid arthritis. It has been studied in this study that whether the disbalance of Th1/Th2 and the changes in activity and silent periodin exist in JRA. There are 30 objectives in this study, among them 12 were male and 18 were female, 8.5 years old on average. The disease course of JRA was 2.5-4.3 years, 14 of them were more than one year. Clinical classification: 11 were panarthritis, 10 were polyarthritis and 9 were pauciarthritis. The control group was 18 children who were healthy examined in OPD, including 7 male and 11 female and they were 9 years old on average. Venous blood samples of these objectives were collected prior treatment, and collected again half or one year post treatment. The concentration of IFN-γand IL-4 in these samples were tested by ELISA. These are results: (1) The concentration of IFN-γin JRA group was higher (median 18.84±3.92pg/ml) than the control group (median 10.68±3.55pg.ml), the deviation was significant between them (P<0.01). The concentration of IL-4 in JRA group was lower (median 1.86±0.54pg/ml) than the control group (median 2.45±0.45pS/m1), there was significant difference between them(P<0.05). The rate of IFN-γ/IL-4 in control group and JRA group were 4.43 ±1.23pg/ml and10.13 ±2.15pg/ml, respectively.The IFN-γ/IL-4 rate in JRA group was higher (P<0.01). (2)The concentration of IFN-γin different type JRA groups, panarthritis, polyarthritis and pauciarthritis were 18.96±6.87pg/ml, 17.44±5.59pg/ml, 16.38±6.25pg/ml, respectively, and the concentration of IL-4 were 2.02±0.56pg/ml, 1.82±0.73pg/ml, 1.74±0.35pg/ml, respectively. There was no significant difference between groups (P>0.05). (3)In different JRA disease course: In group of the disease course under one year, the concentration of IFN-γwas 15.58±5.77pg/ml and IL-4 was 1.96±0.65pS/ml, when above one year, IFN-γwas 21.23 ±6.82pg/m1 and IL-4 was 1.52 ±0.34ps/m1. There was significant difference between these two groups (P<0.01). (4) Prior treatment group and post-treatment half to one year group. The concentration of IFN-γwas 18.84±3.92pg/ml for the prior treatment group and 11.53±2.42pg/ml for the post-treatment group, as for as IL-4, 1.86±0.54pg/ml for prior treatment group and 2.35 ±0.57pg/ml for the the post-treatment group. Comparison of these two groups, there wassignificant difference (P<0.01). (5)The relationship between the ratio of IFN-γ/IL-4 and the JRA proceeding was positive correlation (r=0.86, P<0.01). IFN-γis a very important factor in immune response and inflammatory reaction, regulating the proliferation and differentiation of T and B cells, activating rhagiocrine cell, natural killer cell, vascular endothelial cell and fibroblast, promoting the differentiation of CDs+T to killer cells and inhibiting the Th2 cells producing their cytokines. It's found in this study that the concentration of IFN-γin patients was increased very much, which demonstrated that IFN-γwas over excreted, the factors promoting inflammation were hyperactivity, and IFN-γinduced immune reactions and resulted in synovial membrane damage. IL-4 is a kind of inflammation inhibition factor, which could inhibit monocyte excreting IL-1, TNF, inducing B cell producing IgG. IL-4 is the only cytokine Th cell produced which could transmit the host immune response to humoral immunity, and at the same time, deviate from cell-mediated immunity. In this study, the IL-4 level in JRA patients was lower compared with the control, showing that the inflammation inhibition factors werereduced. And because the high level IFN-γcould depress the producing of IL-4, this demonstrated that the excretion function between this two cytokines could inhibited each other. Th1 cell excretes Th1 type cytokines including IFNγ, IL-2, IL-12, INF-α. IFN-γmainly mediates cellular immunologic response. Th2 cell also excretes Th2 type cytokines including IL-4, IL-5, IL-6, IL-10, IL-13. IL-4 mainly mediates the proliferation and differentiation of B cell. Between these two types cytokines, Th1 cytokines and Th2 cytokines, one type could interact with the other one, and they all are in a dynamic equilibrium state, both Th1 type and Th2 type cytokines keep the normal function of cell-mediated immunity and humoral immunity. In this study, IFN-γrepresents the level of Th1 and IL-4 represents the level of Th2. The high level expression of IFN-γin JRA group patients showed that the Th1 immune response increased, and the low level expression of IL-4 showed the Th2 immune response decreased. The ratio of IFN-γ/IL-4 in the JRA group increased, showing the balance of Thl/Th2 was drift to Th1, the balance of Thl/Th2 in JRA patients was disturbed. It's reported that the CD4+T cell existed in the RA patient's synovial...
Keywords/Search Tags:Th1/Th2
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