Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto’s thyroiditis patients

Abstract

Introduction: The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT). Mycobacterium avium subsp. paratuberculosis (MAP) has been linked to both T1D and HT. Quite a few lines of evidence indicate that autoantibodies against several epitopes belonging to human zinc transporter 8 (ZnT8) cross-recognize the homologous MAP3865c epitopes in both T1D and HT patients. HP may play a role in HT disease, most likely acting through a molecular mimicry mechanism that targets ZnT8 as reported for MAP and the two autoimmune diseases. Methodology: An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antibodies against several epitopes deriving from HP proteins, which are highly homologous to the immunodominant ZnT8 peptides previously identified: ZnT8 178-186 and ZnT8 [186][187][188][189][190][191][192][193][194] . Results: None of the HP peptides tested were significantly recognized when the humoral responses of 92 HT patients and 91 healthy volunteers were analyzed. Conclusions: These findings do not support a triggering role for HP (through ZnT8 mimicking) in HT. If a molecular mimicry phenomenon is taking place, it involves a different self-antigen. Moreover, the negative outcome of the experiments performed stresses the fact that sharing stretches of sequence homology is relevant, but not enough to trigger an antibody-mediated cross-recognition.

Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies

“…Cross-reactivity to the common target sequences and specificity of the homologous anti-MAP/ZnT8 Abs verified by competition assays in previous studies [ 8 ] demonstrated recognition of a transmembrane domain of ZnT8 protein that cannot be evaluated by standard anti-ZnT8 Abs tests which employ a fusion protein combining extraluminal domains. The same ZnT8 region has a high homology with HP-derived peptides already evaluated in association with autoimmune thyroiditis [ 42 ]; in contrast to MAP, anti-HP Abs were detected at very low levels with similar prevalence in children at risk for T1D and the control group providing additional support for the association of MAP with autoimmune diabetes; therefore, responsiveness to MAP-derived antigens in the former group cannot be explained by an increased overall immune reactivity. A high degree of correlation between the homologous peptides further points at their cross-reactivity and segregation within the same sera.…”

Rheumatoid arthritis patient antibodies highly recognize IL-2 in the immune response pathway involving IRF5 and EBV antigens

“…To test the specificity of humoral responses mounted against the selected peptides, 22 HCs and 22 RA patients were randomly selected from the study population and tested for seroreactivity against J0I929_HELPX 1–11 control peptide derived from Helicobacter pylori homologous to human ZnT8 27 . In both groups, half number of samples tested positive to at least one (HCs) or all (RA) of the previously assessed peptides.…”

“…In addition, J0I929_HELPX 1–11 (MIIGGGVSGCA) derived from H . pylori quinone oxidoreductase, homologous to human ZnT8 27 was used as a control peptide. Moreover, wells containing no peptides adsorbed were included as negative control.…”