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Assocication of CTLA-4 Gene Products and CD154 with Autoimmune Throid Disease

Author: PanHongZhen
Tutor: DongJiXiang
School: Suzhou University
Course: Endocrinology
Keywords: autoimmune thyroid disease cytotoxic T-lymphocyte antigen 4 CD40L
CLC: R581
Type: Master's thesis
Year: 2011
Downloads: 19
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Abstract

Objective To observe the expression and significance of cells cytotoxic T- lymphocyte antigen 4 (CTLA-4, CD152), CD154 (CD40L)on the T cells and the serum level of serum soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4) in adult autoimmune thyroid disease.Methods The studied subjects include 23 cases of untreated GD patients(GD before treatment group), 20 cases of clinical remission after treatment patients with GD(GD clinical remission group ),12 patients with Graves Ophthalmopathy(GO) (GO group) ,10 cases of Hashimoto thyroiditis(HT) patients(HT group) and 15 healthy volunteers(normal control group).the expression of cells cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152)、CD154 on the T cells were measured by Flow cytometry; Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of sCTLA-4, And thyroid function and autoantibodies were detected by chemiluminescence.The methods of statistical analysis included Kruskal-Wallis H test among groups,Independent sample t test or Mann-whitney U test beween two groups, Pearson or Spearman correlation analysis between two groups.Results 1 The serum levels of sCTLA-4 in control group, GD before treatment group , GD clinical remission group,GO group and HT group were respectively 0.877±1.143(ng/ml),11.779±14.141(ng/ml),8.588±10.614(ng/ml),22.364±29.394(ng/ml),7.848±8.713(ng/ml).Compared with the normol control group,the remaining four groups significantly increased(P<0.01); the level of sCTLA-4 between GD before treatment group and GD clinical remission group was no significant different(P>0.05);the level of sCTLA-4 in GO group significantly increased compared with GD before treatment (P<0.05). 2 The percentage of CD3~+CD152~+T、CD4~+CD152~+T in normal control group, GD before treatment group,GD clinical remission group,GO group and HT group were respectively 2.60±2.26and3.07±2.78,10.45±4.21and7.99±3.12,5.45±1.78and4.00±1.93,14.05±4.30and11.55±3.20,0.95±0.77and1.35±0.76.Compared with the normal control group, the percentage of CD3~+CD152~+T、CD4~+CD152~+T was significantly higher in GD before treatment group,GD clinical remission group,GO group,( P<0.05). GD clinical remission group significantly decreased compared with GD before treatment group(P<0.01). Compared with the control group,The percentage of CD3~+CD152~+T、CD4~+CD152~+T was significantly low in HT group(P<0.05).3 The percentage of CD4~+CD154~+T in normal control group, GD before treatment group,GD clinical remission group,GO group and HT group was respectively 0.59±12.96,27.09±7.89,29.50±14.26,29.45±15.49,24.78±14.41. Compared with the normal control group or GD before treatment group, The percentage of CD4~+CD154~+T in the remaining groups had no significantly difference(P>0.05).4 The correlation of CTLA-4 gene products and CD154 with clinical parameters in GD before treatment group or HT group: (1)There were no correlation of the level of sCTLA-4 and the percentage of CD3~+CD152~+T,CD4~+CD152~+T,CD4~+CD154~+T with FT3,FT4,TSH,age.(P>0.05).(2) There were no difference of sCTLA-4 between men and women group;There were no diference of sCTLA-4 between smoking and non-smoking group too.(3) The percentage of CD3~+CD152~+T(r=0.447),CD4~+CD152~+T(r=0.424) was positively correlated with TRAb in GD before treatment group(P<0.05).There were no correlation of sCTLA-4 and the percentage of CD4~+CD154~+ with TPOAb,TGAb,TRAb in GD before treatment group(P>0.05).(4) The percentage of CD3~+CD152~+T(r=-0.841),CD4~+CD152~+T(r=-0.706) was negatively correlated with TGAb in HT group(P<0.05)There were no correlation of sCTLA-4 and the percentage of CD4~+CD154~+ with TPOAb,TGAb,TRAb in HT group(P>0.05).Conclusion 1 The serum level of sCTLA-4 in GD group or HT group was higher than that in normal control group. It suggests that sCTLA-4 may be involved in the development of AITD through the interaction with the costimulatoty molecules B7. There were no correlation of sCTLA-4 with age, sex, smoking, thyroid hormones, thyroid autoantibodies and therapy. It suggests that gene maybe determine the serum level of sCTLA-4 which was not affected by external environment such as smoking and treatment.Its participation in the process of AITD may be unrelated to the production of thyroid autoantibodies.2 The level of sCTLA-4 in GO group was much higher than that in GD before treatment group. It suggests that sCTLA-4 was involved in the occurrence and development of GO.sCTLA-4 may a sensitive indicator which indicates the occurrence of GO.3 The expression of CD3~+CD152~+T and CD4~+CD152~+T was significantly abnormal in AITD;The level of CD152 was associated with thyroid autoantibodies; GD clinical remission group decreased significantly compared with GD before treatment group. It speculates that CD152 may play a role through the production of autoantibodies in AITD; The treatment of AITD may play an inmmune adjustment role.4 Compared with the percentage of CD4~+CD154~+ of the control group and GD before treatment group, the percentage of CD4~+CD154~+ in the remaining groups had no significantly difference. There were no correlation of the percentage of CD4~+CD154~+ with FT3,FT4,TSH,TPOAb,TGAb and TRAb.The role of CD154 as an important costimulatory molecule ligand in AITD needs further study.

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