Naslov
T-cell gene expression patterns affect quantitative phenotypic characteristics of Hashimoto's thyroiditis

Autori
Štefanić, Mario ; Tokić, Stana ; Glavaš-Obrovac, Ljubica ; Mihaljević, Ivan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 14th International Thyroid Congress / Schlumberger, M - , 2010, OP-0242

Skup
14th International Thyroid Congress

Mjesto i datum
Pariz, Francuska, 11.09.2010. - 16.09.2010

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Genes ; Hashimoto’s thyroiditis ; T-cells

Sažetak
Abstract: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disorder mediated by deregulated T-cell responses. Several gene candidates encoding immune regulators have been implicated in HT etiology, including vitamin D receptor (VDR), cytotoxic T-lymphocyte antigen- 4 (CTLA-4), CD28 and CD45 transcripts. Aim: To evaluate clinical implications of VDR, CTLA-4, CD28 and CD45 mRNA expression profiles in peripheral T-cells of HT patients. Methods: 44 HT patients (3 male, mean age 47±14.4 years) and 46 geographically-matched, euthyroid, TPOAb-negative controls without a family history of autoimmune disorders (10 male, 42±12.3 years) were recruited. HT was diagnosed by positive TPOAb-IgG (median titer 302 IU/mL, interquartile range 88-1440 IU/mL), ultrasonographic and cytopathologic findings on FNAB and/or biochemical hypothyroidism (median TSH 5.27 mU/L, interquartile range 3.11- 13.8 mU/L). Untouched T-lymphocytes were negatively isolated from peripheral blood using magnetic beads. Total mRNA was extracted and gene expression studied by RT-PCR and ImageQuant method relative to GAPDH products (%). Biochemical data and goitre volume were compared to gene expression data by rank correlations and robust regression procedures. Results: VDR, CTLA-4, CD28 and five isoforms of CD45R mRNA (ABC, AB, BC, B and 0) were successfully detected in at least 95% of samples. Total mRNA expression did not differ by case- control status, gender and need for hormone replacement therapy. A family history of thyroid disorders (n=12) was associated with lower CD45RABC mRNA expression (P=0.009, 11.4±2.9 vs 20.9±1.8, HT group). CD28 (β=0.236±0.062, R2a~28%, P<0.001, HC3 estimators) and CTLA-4 mRNA levels (β=-0.09±0.04, R2a~7%, P=0.03) were independently associated with CD45RBC expression in HT patients. A strong age- dependent shift toward CD45R0 expression was seen (Spearman's ρ=0.341, P=0.027, n=42), as judged by CD45R0/RB ratio (ρ=0.462, P=0.002 ; R2a~19%, β=0.0094±0.0029, P=0.0023). Moreover, VDR mRNA expression was independently and inversely associated with CD45R0 mRNA expression (R2 a~9%, β=-0.237±0.096, P=0.018) and, particularly, CD45R0/RB ratio (β=-0.0038±0.001, P=0.0017, R2a~16%, HT group). Conversely, a positive correlation, independent of the case- control status, was detected between age-corrected VDR and CTLA-4 mRNA levels(ρ=0.26, P=0.014, R2a~6%, β=0.273±0.113, P=0.018), as well as VDR and CD45RABC mRNA (R2a~5%, β=0.093±0.045, P=0.04). CD45RAB, adjusted for the CD45RABC level, was significantly higher in female participants (14.7±0.77 vs 10.4±1.93, P=0.042). CD45RBC and B mRNA expression was highly related to CD28 levels in both groups (P<0.002). At diagnosis, CTLA-4 mRNA expression was inversely related to age- and FT4-corrected logTSH values (β=-0.0047±0.002, P=0.026, R2a~5%). Subsequently, age (β=-0.013±0.004, P=0.0017) and VDR mRNA expression (β=0.0045±0.0017, P=0.013, R2 a~7%) were the only significant predictors of FT4-corrected FT3 values. Conclusion: Unlike naive T-cells which preferentially express large CD45R isoforms (ABC/AB/BC), activated and memory T lymphocytes express the shortest one, CD45R0. Collectively, CD45, CTLA-4 and VDR network interplay is differentially controlled during lymphocyte development and activation and affects HT disease characteristics through poorly characterized mechanisms. Further analysis by combining qPCR and FACS is needed.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA