Detection of human antibodies binding with smooth and rough LPSs from Proteus mirabilis O3 strains S1959, R110, R45

Abstract

Bacteria of the genus Proteus of the family Enterobacteriaceae are facultative human pathogens responsible mainly for urinary tract and wound infections, bacteremia and the development of rheumatoid arthritis (RA). We have analyzed and compared by ELISA the titer of antibodies in plasmas of healthy individuals and in sera of rheumatoid arthritis patients recognizing a potential host cross-reactive epitope (lysine-galacturonic acid epitopes) present in Proteus lipopolysaccharide (LPS). In our experiments LPSs isolated from two mutants of smooth Proteus mirabilis 1959 (O3), i.e. strains R110 and R45, were used. R110 (Ra type mutant) is lacking the O-specific polysaccharide, but possesses a complete core oligosaccharide, while R45 (Re type) has a reduced core oligosaccharide and contains two 3-deoxy-d-manno-oct-2-ulosonic acid residues and one of 4-amino-4-deoxy-l-arabinopyranose residues. Titer of P. mirabilis S1959 LPS-specific-antibodies increased with the age of blood donors. RA and blood donors’ sera contained antibodies against S and Ra and Re type of P. mirabilis O3 LPSs. Antibodies recognizing lysine-galacturonic acid epitopes of O3 LPS were detected by ELISA in some plasmas of healthy individuals and sera of rheumatoid arthritis patients. RA patients antibodies reacting with P. mirabilis S1959 S and R LPSs may indicate a potential role of anti-LPS antibodies in molecular mimicry in RA diseases.

Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus mirabilis O3 (S1959) Lipopolysaccharide May React with Collagen Type I

“…LPS R45 showed the highest level of antibody binding. This contrasts with our previous finding that R45 bound the least antibodies in human plasma [ 22 ]. The difference can be explained by the surface to which the antigen was attached.…”

“…The differences may be explained by the carbohydrate structure of LPS, and differences in antibodies production. On the other hand, the lack of correlation between age and IgG antibodies reaction did not confirm previous studies showing that the amount of antibodies against LPS O3 increases with age [ 22 ].…”

“…Previous studies showed a significant difference in the level of antibodies to lysine-containing LPS O3 between RA patients and healthy donors [ 26 ]. Moreover, it has been shown that human sera produce antibodies against the amide of galacturonic acid and lysine present in the polysaccharide chain of LPS O3, and it is possible that antibodies against Lys-GalA react with collagen I [ 22 ]. Lysine is the most common amino acid incorporated in the polysaccharide chain of P. mirabilis LPS, and it is an important epitope responsible for cross-reactions between serogroups of bacterial LPS which confirms the results of animal studies [ 12 , 20 , 21 ].…”

“…LPSs extracted by phenol-water method from P. mirabilis strains S1959 (O3), PrK49/57 (O26), 50/57 (O27) contained lysine in O antigen repeating unit, and LPS of P. mirabilis HI 4320 (O10) contained lysine in the core region. LPSs extracted using the PCP method from Ra mutant of P. mirabilis S1959 (R110) had no O polysaccharide part, and the Re mutant of P. mirabilis 1959 (R45) had only a fragment of the lipid A and two rests of Kdo [ 22 , 35 , 36 ].…”

“…Moreover, it have been shown that antibodies against Lys-GalA can be partially adsorbed by collagen I. This suggests that antibodies against P. mirabilis LPS might cross-react with human tissue [ 22 ]. Studies based on the detection and description of neo-epitopes in arthritis show that enzymatic degradation of joint collagen, including collagen I, may affect biomarkers production useful in diagnostics indicates a role of collagen type I in disease development [ 23 ].…”