Autoantibodies to a specific peptide epitope of human Hsp60 (ATVLA) with homology to Helicobacter pylori HspB in H. pylori‐infected patients

Abstract

Chmiela M. Autoantibodies to a specific peptide epitope of human Hsp60 (ATVLA) with homology to Helicobacter pylori HspB in H. pylori-infected patients. APMIS 2019; 127: 139-149.Helicobacter pylori (Hp) may initiate autoimmunity as a result of molecular mimicry. The aim of this study was to compare the level of IgG antibodies to a specific epitope (P1 peptide) of human heat shock protein (Hsp)60 homologous to Hp Hsp60 (HspB) in the sera of healthy donors (HD), patients with Hp-related gastritis or coronary heart disease (CHD), uninfected or with Hp infection confirmed by rapid urease test, histological examination (dyspeptic patients) the 13 C urea breath test ( 13 C UBT), and anti-Hp antibodies (healthy donors, CHD patients). The Anti-P1 IgG induction by Hp was verified by adsorption of sera with these bacteria and by experimental immunization of Caviae porcellus with Hp. Cytokine secretion by THP-1Blue TM monocytes in response to P1 was also assessed. Anti-P1 antibodies were detected in patients with gastritis or CHD infected with Hp and they were not found in uninfected individuals or asymptomatic carriers. No antibodies were raised against P2 in any group. Reduced cross-reactivity to P1 was exhibited by sera adsorbed with Hp. Caviae porcellus infected with Hp produced anti-P1 autoantibodies. THP-1XBlue TM monocytes responded to P1 by production of proinflammatory cytokines. Autoantibodies against P1 in Hp-positive patients with gastritis or CHD and upregulation of proinflammatory cytokines by P1 may contribute to the pathogenesis of Hp infection.

Medical, Genomic, and Evolutionary Aspects of the Peptide Sharing between Pathogens, Primates, and Humans

“…Molecular mimicry and the consequent potential cross-reactivity following infections have been repeatedly described in humans. [1][2][3][4][5][6][7][8][9][10][11][12] Such cross-reactivity is not evident in experimental infections of primates. 13 Actually, following preclinical studies performed in primates [14][15][16][17][18] as recommended by the Food and Drug Administration, 19 the reports declare that primate active immunization by pathogen vaccine administration is well tolerated and exempt of relevant events.…”

Review: Pathogenesis of Helicobacter pylori infection

“…In Western but not Asian H pylori strains, a linear glucan-heptan linker between these two parts of LPS was identified. This dependence was also shown by the stimulation by ATVLA of human THP-1Blue™ monocytes for the secretion of proinflammatory cytokines 31. IgG class antibodies to synthetic P1 peptide containing ATVLA were detected in patients with gastritis or coronary heart disease (CHD) infected with H pylori as well as in Cavia porcellus inoculated with H pylori, but not in uninfected individuals or asymptomatic H pylori carriers, suggesting a potential role of such antibodies, possibly autoreactive, in the development of H pylori-related disease.…”

“…The study carried out by Gonciarz et al, 31 Furthermore, it was shown that the H pylori genetic region, known as integrating conjugative elements of H pylori T4SS, contains a novel type of T4SS, which is considered as a H pylori virulence factor. 33 However, the structure containing genes encoding components of this system, and the interactions between this T4SS and other virulence factors remain unknown.…”

“…Another study revealed that the LPS of Western and Asian H pylori strains was different in the type of linker between the core oligosaccharide (Glc-Gal-Hep-III-Hep-II-Hep-I-KDO) and attached trisaccharide (GlcNAc-Fuc-Hep) 30. The presence of an alternative linker in LPS of Asian strains and its role in H pylori pathogenesis were suggested because H pylori infection is more severe and symptomatic in Asia than it is in Western countries.The study carried out by Gonciarz et al,31 on a common epitope (ATVLA sequence) of H pylori heat shock protein (Hsp)B and human Hsp60, revealed its immunogenicity. The presence of an alternative linker in LPS of Asian strains and its role in H pylori pathogenesis were suggested because H pylori infection is more severe and symptomatic in Asia than it is in Western countries.The study carried out by Gonciarz et al,31 on a common epitope (ATVLA sequence) of H pylori heat shock protein (Hsp)B and human Hsp60, revealed its immunogenicity.…”

Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes

“…tuberculosis, different herpes virus infections, Dengue virus infections [9,10], hepatitis, or events summarized as "common cold" and "feverish infection" (for review see [5]). This suggests the action of viral or bacterial proteins mimicking antibody targets as first initiating events, as seen in patients with Guillain Barré Syndrome [11,12] or some other antibody-driven diseases [13,14].…”