Study On The Effects Of Iodine/selenium On The Susceptibily To AITD And The Production Of TPO Autoantibodies

Autoimmune thyroid diseases(AITD) are organ specific diseases characterized bythe appearance of high levels of thyroid autoantibodies and a destruction of thyroidtissues and thyroid disfunction frequently. Studies have showed that TPOAb had a closerelationship with the onset and development of AITD. TPOAb have been considered asan important indicator in the diagnosis, curative effect and prognosis of AITD.Environmental factors have an important role in the pathogenesis of AITD. In recentyears, clinical endocrinologists brought forward that the incidence of AITD and the levelsof thyroid autoantibodies seemed to be evaluated, which caused some scholars a highattention. It is unclear whether this phenomena had some relation to the changes of iodineintake after USI. Also some epidemiological studies reported that a high incidence ofAITD had been found in selenium deficient areas. In nature, selenium deficiency is aswide as iodine deficiency and frequently overlaps with each other in the geographicaldistribution.It could hypothesize that in iodine deficient areas after iodine supplementation,selenium deficiency may become more predominant and then influenced the AITDsusceptibility. Whether a certain level of selenium could antagonize the role of escessiveiodine intake in AITD and the detailed mechanism involved in it are not very clear. Sostudying on the relationship between iodine/selenium intake and the development ofAITD and its mechanism, effects of iodine/selenium on the thyroid anutoantigens,immune system and selenium supplementation in the precaution of AITD would providea much higher theoretical and practical significance in the precaution and treatment ofAITD.First part: TGAb,TMAb and TPOAb's behaviour in AITDAITD patients with different thyroid function (including hyperthyroid, hypothyroid,subclinical hypothyroid and those who once suffered AITD but now thyroid function wasrestored to normal) and a certain number of healthy blood donors taken as control wereenrolled in our experiment. The level of TPO Ab, TGAb and thyroid microsomalantibodies(TMAb) as well as thyroid hormones were measured and the relationshipbetween thyroid autoantibodies and thyroid dysfunction was observed. Results:Thepositivity rate of TPOAb was higher than those of TGAb and TMAb in each group,(P＜ 0.01). In restored thyroid function group, the positivity rate and the average positive levelof thyroid autoantibodies were still higher than those of the control group (P＜0.01)while lower than those of hyperthyroid, hypothyroid and subclinical hypothyroid groupexcept that no statistical differences of the positive level of both TGAb and TMAb werefound among these groups. Conclusion: Our experiment further ascertained that TPOAbwere not only an important marker of thyroid autoimmune,but also had more clinicalvalue rather than TGAb and TMAb for those thyroid dysfunction patients to be diagnosedas AITD.Second part: TGAb and TPOAb's behaviour in rats and mice with different EATsusceptibility.EAT susceptible Lewis rats and unsesceptible Wistar rats, femal, 4-6 weeks old,weighing 100-150g and EAT susceptible CBA/CAJ mice and unsesceptibe Balb/cmice,femal,6-8 weeks old, weighing 18-20g were all used as experimental animals inthis experiment. Lewis and Wistar rats were randomly divided into two groupsrespectively, ie, EAT group(L/EAT, W/EAT) and control group(L/Control,W/Control).Also, CBA/CAJ mice and Balb/c mice were randomly divided into twogroups respectively, ie, EAT group(C/EAT, B/EAT) and control group(C/Control,B/Control).Porcine TG emulsified with the same volume of complete Freud's adjunct(CFA) were used to immunize the rats from each EAT group for inducing EAT. Twoweeks after the last immunization, all rats and mice were sacrificed and their blood andthyroid glands were taken. The pathological changes in the thyroid tissues were observedand the levels of thyroid autoantibodies (TGAb and TPOAb) and thyroid hormones (TT₃and TT₄) were determined by Radioimmuno Assay (RIA).Results: The levels of thyroidautoantibodies (TGAb and TPOAb) in EAT groups were significantly increased afterEAT induction comparing with those of control groups in both rats and mice. The levelsof TGAb showed no statistical difference between L/EAT (Lewis) and W/EAT (Wistar)groups while the levels of TPOAb in L/EAT (Lewis) were remarkably higher than thoseof W/EAT (Wistar) groups. Contrarily, there was no significant difference of the levels ofTPOAb between C/EAT(CBA/CAJ) and B/EAT (Bablb/c) groups while the levels ofTGAb in C/EAT(CBA/CAJ) group were higher than B/EAT (Bablb/c) group, P＜0.05.Conclusion: The levels of TPOAb showed high sensitivity in EAT susceptible rats. EATinduced Lewis rats showed not only a obvious inflammatory reaction in the thyroidtissues but also a high levels of TPOAb, so Lewis rats would be choosed as theexperimental animals for the third part.Third part: Study on the effects of iodine/selenium on the susceptibily to AITD and theproduction of anti-TPO autoantibodies. Female Lewis rats were used in this part of the experiment. Rats for EAT inductionwere randomly divided into five groups, ie,â‘ low selenium and normal iodine EATgroup (L_seN_I—EAT)â‘¡low selenium and high iodine EAT group (L_SeH_I—EAT)â‘¢normalselenium and high iodine EAT group (N_SeH_I—EAT)â‘£normal selenium and normaliodine EAT group (N_SeN_I—EAT)⑤normal selenium and normal iodine group(N_SeN_I). Rats for the experiment of antigen presentation were randomly divided into fourgroups, ie,â‘ low selenium and normal iodine group (L_SeN_I)â‘¡low selenium and highiodine group (L_SeH_I)â‘¢normal selenium and high iodine group (N_SeH_I)â‘£normalselenium and normal iodine group (N_SeN_I). All rats were fed by a special diet with lowerselenium and iodine in it and drunk ion-free water containing different levels of iodineand selenium for 3 months. Then EAT were induced forâ‘ -â‘£and those rats fromgroups for antigen presentation experiment were tested too. The levels of selenium in theserum, the morphological changes in the thyroid tissues, the appearance of CD3 positivelymphocytes, the levels of thyroid autoantibodies (TPOAb and TGAb), the levels ofthyroid hormones (TT₃ and TT₄), the activity of GSH-PX, the levels of MDA in liver,the levels of IL-2 in the culture supernate of celiac macrophages and the levels ofexpressions of IFN-γ, IL-4, IL-10 and CD86 mRNA in the spleen were all determined.Results showed that the levels of selenium in both the L_SeN_I—EAT and L_SeH_I—EATwere significantly lower than control group. The incidence of EAT in L_SeH_I—EAT werethe highest(about 80%) and the inflammatory reaction were most severe whilecomparing with the other groups. Comparing with N_SeN_I—EAT, Both the levels of TGAband TPOAb in N_SeH_I—EAT and L_SeH_I—EAT were obviously increased while onlyTPOAb in L_SeN)I-EAT significantly increased and no statistical changes in the levels ofTGAb were found. The levels of TT3 in the serum in N_SeH_I-EAT, L_SeN_I-EAT and L_SeH_I-EAT were remarkably decreased comparing with control group while the levels of TT4decreased in N_SeH_I-EAT while decreased in L_SeN_I-EAT and L_SeH_I-EAT. The activity ofGSH-PX in N_SeH_I-EAT, L_SeN_I-EAT and L_SeH_I-EAT were all obviously lower thancontrol, especially in the latter two groups while the levels of MDA in these threegroups increased. The levels of the expression of IFN-γmRNA in N_SeH_I-EAT, L_SeN_I-EAT and L_SeH_I-EAT were all higher than that of N_SeN_I-EAT especially in L_SeH_I-EATwhile no significant differences were found among these four groups. The levels of theexpression of IL-10 mRNA in L_SeH_I-EAT decreased comparing with N_SeH_I-EAT whileno statistical changes were found among N_SeH_I-EAT, L_SeN_I-EAT and N_SeH_I-EAT.Comparing with N_SeN_I, the levels of IL-2 in the culture supernate of celiac macrophagesin N_SeH)I increased significantly while decreased in L_SeN_I significantly too and no statistical changes were found between L_SeH_I and N_SeN_I. The expression of CD86 mRNAin N_SeH_I were higher than that of N_SeN_I, P＜0.05 and no significant differences wereshown among L_SeN_I, L_SeH_I and N_SeN_I. Conclusion: 1. Both high iodine and low seleniumintake would increase the incidence of EAT and aggravate the inflammation in thyroidtissues of Lewis rats. In addition, high iodine would cooperate with low selenium in theinduction of EAT. 2. high iodine intake would increase the levels of TGAb and TPOAbin the induced EAT Lewis rats while low selenium intake only increase the levels ofTPOAb. 3. The immune mechanism aggravating the formation of EAT by high iodine orlow selenium intake is proposed as follows (1) high iodine or low selenium intake couldbreak the balance of Th1/Th2 cytokines and present a Th1 predominance. Th1 cytokinescould participate the inflammatory reaction in the thyroid tissues leading to the damagesof the tissues. (2) high iodine or low selenium intake would boost the production ofTPOAb, which could aggravate the damage in the thyroid tissues by ADCC or CDC.(3)high iodine could promote the presentation function of macrophages to a higher statethan normal, which became an important factor for the formation of EAT. low seleniumcould weaken the ability of recognizing and presenting OVA antigen of celiacmacrophages. Considering that a weak function of recognizing and presenting antigencould affect the clearing of the degraded self-antigen, senile cells and destroyimmunological homeostasis, which may become an inducing factor in EAT. 4. Seleniumsupplementation could antagonize the action of high iodine in the induction of EAT bymany ways such as adjusting the immune function, improving the thyroid function,decreasing the production of TPOAb and reducing the oxidation injury. Therefore, Areasonable supplementation of trace element based on different region would have morepractical value in the control of AITD,...