Authors
Ulrich Loos, Johannes W. Dietrich, Siegrid Bräth
Abstract
Introduction: TPO-Ab and TRAb are biomarkers of thyroid autoimmunity. Here we measured biological activity of thyroid autoimmunity (TA) by a TSH receptor bioassay in sera from patients with HD.
Methods: fT4, fT3, TSH, TPO-Ab, TRAb (Thermo Fisher) and sTRAb [1] were tested to confirm the diagnosis. Stimulating (sBIO positive>ca. 1.2–1.3 SI) and blocking (bBIO positive<0.7–0.8 SI) activity were measured by a TSH receptor TRE reporter gene bioassay in HEK cells [2]. Groups of patients with TA: 1. Hypothyroid and only TPO extremely positive; 2.Hypothyroid and TPO-Ab, TRAb and sTRAb moderately (a) and highly (b) positive. 3. In an extended G1 collective (52 only TPO-Ab positive patients) the correlation between TPO-Ab and bBIO values was studied. Statistical distributions were compared with Welch’s t test and Pearson’s correlation.
Results: Means ± SEMs were: G1: TPO-Ab=7713.9±1403 U/ml, TRAb<1 IU/L, sTRAb=0.16±0.161 IU/L, bBIO=0,495±0.055 SI (n=10). G2a: TPO-Ab=2355.1±264.4 U/ml, TRAb=3.3±2.7 IU/L, sTRAb=2.2±2.1 IU/L, bBIO= 1.022±0.08 SI (n=20). G2b: TPO-Ab=2544±625.2 U/ml, TRAb=26.8±14.3 IU/L, sTRAb=24.7±7.6 IU/L, sBIO= 1.32±0.28 SI (n=5). Signal transduction was impaired in sera with high TPO-Ab titers in G1 (p<0.001) as compared to G2a and in total there was a significant correlation between TPO Ab titers and inhibition of TSH signaling in the blocking assay (r=04691, p<0.001, n=52). Interestingly, in G1 TRAb and sTRAb were negative, however positive in G2. CRE signaling could be stimulated in sera containing high TRAb (p<0.001). In G2b stimulatory character of coexisting TRAb values was detected.
Conclusion: Sera in HT inhibit cAMP accumulation increasingly with the height of TPO-Ab titers in none thyroidal cells harboring the TSHR and CRE-AP suggesting cAMP pathway is involved in the pathogenesis of hypothyroidism in HD.
References: 1. Horm Metab Res. 2015 Nov;47(12):880-8; 2. Poster ITC Paris 2010 P-0020: https://bcom. mcigroup.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=32320
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