A Role For Serum Concentration Of CD40 And CD40 Ligand (CD40L) In Graves' Disease

Objective: CD40 / CD40 ligand (CD40L) is one of the costimulatory signals about T-cell activation, by inducing cell activation and cytokine production, Which regulates regulating cell-mediated humoral immunity and to participate in intracellular signal transduction, in a variety of self -play a role in autoimmune disease. Graves disease (Graves Disease, GD) is a common organ-specific autoimmune disease, TSH receptor antibody (TRAb) in Graves disease in the pathogenesis of its major role. Can be expressed as a simple clinical hyperthyroidism (Hyperthyroidism), can also be expressed as function of normal Graves ophthalmopathy (Graves ophthalmopathy, GO), or hyperthyroidism and eye disease exist. Organ for the effects of autoimmune thyroid and retrobulbar organizations, Graves disease Hyperthyroidism in the thyroid gland lymphocytic infiltration of a large number of pathological features.In recent years, the incidence of GD was significantly increased, but the pathogenesis of the disease is still not very clear.In recent years, co-stimulatory signal in the pathogenesis of Graves in the role of more and more attention, so to strengthen research in this area contribute to a better reveal the immune pathogenesis of Graves disease.The topics to be Graves disease by measuring the anti-thyroid drug treatment before and after the formal relapse after remission and healthy control subjects in plasma levels of CD40/CD40L and its relationship with thyroid function and other indicators of the relationship between the immune to further clarify the CD40/CD40L in the Graves disease the role of the immune pathogenesis.Methods: 75 patients with Graves' disease in primary experimental groups for⑴untreated group: the initial issuance of hyperthyroidism without treatment, a total of 30 cases.⑵remission group: after methimazole or propylthiouracil formal treatment, remission (defined as symptoms of hyperthyroidism significantly reduced or disappeared, serum FT3, FT4, TSH returned to normal and stable for a month), a total of 25 cases.⑶recurrence group: hyperthyroidism after antithyroid drugs for the treatment of at least 1.5 years, recurrence after stopping, a total of 20 cases. The normal control group: selected from our hospital medical centers for routine health examination, age, sex matched and almost no infection within a month, no history of thyroid disease and thyroid disease, family history, no history of other autoimmune diseases, and family history of A total of 25 cases. Gender and age no difference among the three groups. Thyroid function and thyroid auto-antibodies: early morning fasting blood collected 5ml, separation of serum detection of TSH, FT3, FT4, TPOAb, TGAb (chemiluminescence), TRAb, TSAb (using ELISA method).Serum CD40, CD40L assay (double-antibody sandwich ELISA method).All data used SPSS17.0 software statistics, measurement data to the mean plus or minus standard deviation (?x±s), said multiple sets of data one-way ANOVA was used to compare between the two groups using t or t 'test was used for treatment, the rate of was used to compare between the X2, serum CD40, respectively, with other indicators of serum CD40L for linear correlation analysis and multiple linear regression analysis. Significance test with P said in the P <0.05 for the difference was significant.Results:1,Serum FT3, FT4, TSH the determination of the results,Graves' disease serum FT3, FT4 levels in the initial issuance of the untreated group (23.88±5.69,88.35±35.27pmol / L) and the recurrent group (19.49±7.59,62.07±37.49pmol / L) was significantly higher than remission group (4.32±0.47,18.89±6.78pmol / L) and normal control group (5.80±0.64,19.97±3.72pmol / L), the differences were significant (P <0.01); untreated group and relapse group TSH levels were 0.0089±0.014uIU / L, 0.0049±0.0035uIU / L, significantly lower than the remission group (1.54±0.99uIU / L) and control group (1.67±1.07uIU / L) levels, the difference was significant (P <0.01); remission groupwith the control group between the serum FT3, FT4, TSH level was no significant difference.2,Serum TPOAb, TGAb the determination of the resultsGraves' disease in primary untreated group, relapse group and ease the levels of serum TPOAb were significantly higher than the normal control group (respectively, TPOAb: 194.52±151.32,198.96±128.78,192.34±135.46 VS 70.88±57.69pmol / L), difference there was a significant (P <0.01); untreated group, remission and relapse group no significant difference between the TPOAb levels (P> 0.05); TPOAb positive rate of Graves' disease in primary untreated group, recurrence group and the remission group were significantly higher than the normal control group (respectively: 56.7%, 60%, 44% VS 8%), the difference was significant (P <0.01), untreated group, between the remission and relapse group no significant difference in positive rate of TPOAb(P> 0.05); Graves disease in primary untreated group, relapse group and ease the levels of serum TGAb were significantly higher than normal control group (respectively TGAb: 181.67±121.80,215.24±135.37,209.34±118.56 VS 52.77±42.46pmol / L), the differences were significant (P <0.01); untreated group, remission and relapse group no significant difference between the TGAb levels (P> 0.05); TGAb positive rate of Graves' disease in primary untreated group, recurrence group and the remission group were significantly higher than the normal control group (respectively: 56.7%, 60%, 44% VS 8%), the difference was significant (P <0.01), untreated group, remission and relapse between groups TGAb no significant difference in positive rate (P> 0.05).3,Serum contents of TRAb and TSAb determination in various groupsGraves' disease in primary untreated group, relapse group and ease the levels of serum TRAb levels and positive rates were significantly higher than the normal control group (respectively, TRAb: 1.27±0.27,76.7%; 1.28±0.24,80%; 1.07±0.24, 52% VS 0.85±0.16,0%), the differences were significant (P <0.01); is not between the treatment group and relapse group level and positive TRAb was significantly higher than the remission group, the difference was significant (p <0.05), no between treatment group and relapse group level and positive rate of no significant difference (P> 0.05).Graves' disease in primary untreated group, relapse group and ease the levels of serum TSAb levels and positive rates were significantly higher than the normal control group (respectively, TSAb: 1.16±0.33,76.7%; 1.19±0.39,75%; 0.98±0.29, 40%; VS 0.84±0.21,0%), untreated group and relapse group and the control group between the TSAb levels (p <0.01) and the positive rate (p <0.05) There was a significant difference in remission group and the control TSAb levels between groups (p <0.05) and the positive rate (p <0.01) are also significant differences. But not between the treatment group and relapse group level and positive rate of no significant difference (P> 0.05).4,The serum concentrations of CD40 and CD40L determination resultsGraves' disease in primary untreated CD40 serum concentration (56.74±26.39pg/ml) and the recurrent group (52.34±20.61pg/ml) was significantly higher than remission group (28.60±15.55 pg / ml) and normal control group (23.77±9.89pg/ml), the differences were significant (p <0.01).Newly diagnosed untreated group and relapse group, treatment group and the normal control group mitigate between the concentrations of serum CD40 was no significant difference (p> 0.05).Graves disease in primary untreated serum CD40L concentration (27.96±8.16pg/ml) and the recurrent group (22.16±11.40pg/ml) was significantly higher than remission group (16.11±4.57pg/ml) and normal control group (13.31±4.81pg/ml), the differences were significant (p <0.01).Remission group and normal serum CD40L levels between the control group no significant difference (p> 0.05).Newly diagnosed untreated serum CD40L concentrations above recurrence group, the difference was statistically significant (p <0.05).5,Correlation of serum CD40,CD40L,FT3, FT4, TSH, TPOAb, TGAb, TRAb, and TSAbSerum CD40 levels and serum FT3, FT4, TSH levels between the non-correlation (correlation coefficients were 0.133,0.109, -0.092, p> 0.05); serum CD40 levels of TPOAb, TGAb was a positive correlation (r = 0.325, p <0.01; r = 0.257, p> 0.05); serum CD40 levels and serum TRAb, TSAb no correlation between the level (r = 0.05,0.044; p> 0.05).Serum CD40L levels and serum FT3, FT4 levels were positively correlated (r = 0.346,0.398; p <0.01), and TSH levels were negatively correlated (r =- 0.279; p <0.05); serum CD40L levels of TPOAb, TGAb was a positive correlation(r = 0.31, 0.338; p <0.01); Serum CD40 levels and serum TRAb, TSAb levels were positively correlated (r = 0.091, 0.048; p> 0.05).CD40L levels of serum CD40 levels were positively correlated (r = 0.486, p <0.01).Serum TPOAb, TGAb of serum FT3, FT4, TSH was no correlation between the level (r = 0.17,0.16, -0.21; 0.20,0.18, -0.19, p> 0.05); serum TRAb, TSAb and serum FT3, FT4, TSH there is no correlation between levels (r = 0.15,0.05, -0.18; 0.19,0.09, -0.18, p> 0.05).Multiple linear regression analysis: each of FT3, FT4, TSH as the dependent variable, CD40, CD40L, TPOAb, TGAb, TRAb, TSAb for the purpose of multiple linear regression analysis showed that: CD40L levels are affected FT3, FT4, TSH (respectively R = 0.83,0.88,0.56; p <0.01); CD40, TPOAb, TGAb, TRAb and TSAb levels of FT3, FT4, TSH had no significant effect the change.Conclusion: This trial confirms that in the absence of treatment and relapse of Graves disease in the serum CD40, CD40L levels were significantly increased, especially in the former increased more markedly, by the anti-thyroid drug treatment of its level gradually decreased, FT3, FT4, TSH levels to normal When the levels returned to normal; serum levels of CD40 and CD40L positive correlation; serum CD40L levels and FT3, FT4, TSH levels significantly correlated, while the latter is the significant factors, serum CD40, TPOAb, TGAb, TRAb, TSAb level and thyroid function parameters Quewu correlation between serum CD40, CD40L levels were and TPOAb, TGAb level was positively correlated with serum TRAb, TSAb no correlation between levels; shows CD40, CD40L levels may reflect autoimmune Graves disease status , CD40, CD40L and TRAb, TSAb may adopt different mechanisms play a role in the pathogenesis of Graves disease. CD40/CD40L, as is to produce the first two signals, one of the main elements can be used as peripheral blood of patients with autoimmune thyroid disease, a new marker, so as to disease diagnosis, prognosis, treatment and even prognostic assessment and prediction of recurrence provides a new idea and choice...