Susceptibility to Thyroid Disorders in Hepatitis C Luigi Muratori, Dimitrios P. Bogdanos, Paolo Muratori, Marco Lenzi, Alessandro Granito, Yun Ma, Giorgina Mieli-Vergani, Francesco B. Bianchi, Diego Vergani  Clinical Gastroenterology and Hepatology  Volume 3, Issue 6, Pages 595-603 (June 2005) DOI: 10.1016/S1542-3565(05)00018-2 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 Amino acid (aa) sequence homology between the HCV polyprotein, cytochrome P4502D6 (CYP2D6), and TPO. Boxed sequences represent 3 sets of viral/self homologous peptides constructed for testing by enzyme-linked immunosorbent assay. CYP2D6308–319 of the 1st set overlaps by 6 aa with CYP2D6314–325 of the 2nd set of viral/self mimics. HCV non-structural protein 2 (NS2)792–803 of the 2nd set overlaps by 2 aa with NS2802–813 of the 3rd set. NS5A, non-structural protein 5A. Amino acids in standard single letter code; double dot (:), identical residues; single dot (.), conservative substitution. Clinical Gastroenterology and Hepatology 2005 3, 595-603DOI: (10.1016/S1542-3565(05)00018-2) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Positive (black rectangles) and negative (white rectangles) reactivities against the 3 sets of mimic peptides. Reaction to a given peptide was considered positive when ODtest peptide/ODcontrol was ≥2. Positive OD values are reported. (A) In the LKM1-positive group, 5 patients developed AITD during interferon treatment (LKM/1–LKM/5), 2 had AITD without receiving interferon (LKM/6 and LKM/7), and 10 patients (LKM/8–LKM/17) did not have AITD; of these, only 5 were given interferon (LKM/8–LKM/12). In the LKM1-negative group, 10 patients developed AITD before interferon treatment (HCV/1–HCV/10), 8 did not develop thyroid disorders (HCV/11–HCV/18), and 6 developed AITD after interferon treatment (HCV/19–HCV/24). (B) Results in the HCV-negative control groups: 37 patients with AITD (AITD/1–AITD/37) and 21 patients with type 2 AIH (AIH2/1–AIH2/21) with (*) or without anti-TPO antibodies. HCV NS5A, HCV non-structural protein 5A; CYP2D6, cytochrome P450 2D6. Clinical Gastroenterology and Hepatology 2005 3, 595-603DOI: (10.1016/S1542-3565(05)00018-2) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 Inhibition of antibody binding against HCV non-structural protein 5A (HCV NS5A2334–2345) by preincubation with HCV NS5A2334–2345 (), cytochrome P450 2D6 (CYP2D6)308–319 (□), TPO603–614 (▵), and control peptide (x) of serum LKM/1 (A) and LKM/4 (B). On the vertical axis is the percentage of inhibition of antibody binding to the peptide in the presence of competitor peptide at different concentrations: 0, 25, 50, 100, 200, 400, 800 μg/mL. For all 6 HCV NS5A2334–2345/CYP2D6308–319/TPO603–614 multireactive sera, antibody binding to HCV NS5A2334–2345 was inhibited up to 89% by HCV NS5A2334–2345, up to 82.2% by CYP2D6308–319, and up to 73.1% by TPO603–614, but not with the irrelevant control peptide. Clinical Gastroenterology and Hepatology 2005 3, 595-603DOI: (10.1016/S1542-3565(05)00018-2) Copyright © 2005 American Gastroenterological Association Terms and Conditions