Autoantibodies in HIV‐infected patients: Cross site‐specific hydrolysis of H1 histone and myelin basic protein

Abstract

Histones act as damage‐associated molecules, while anti‐DNA antibodies are directed against histone‐DNA nucleosomal complexes. Myelin basic protein (MBP) plays an important role in the pathogenesis of multiple sclerosis. Autoantibodies (Abs) with enzymatic activities are the distinctive feature of some autoimmune and viral diseases. Abzymes with proteolytic activity against different proteins specifically hydrolyze only these specific proteins. Using chromatography of IgGs on columns with immobilized H1 histone and then by chromatography of the fraction having an affinity for the histone (eluted upon loading) on MBP Sepharose, the anti‐MBP antibodies were obtained. Anti‐H1 antibodies were obtained using these columns in reverse order. IgGs against H1 and MBP effectively hydrolyze both H1 histone and MBP but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H1 histone and MBP by abzymes against these proteins are found. The hydrolysis of MBP by anti‐MBP IgGs occurs at four clusters (22 sites of the hydrolysis) locating at four known antigenic determinants of MBP. Anti‐H1 Abs hydrolyze MBP only at one cluster (11 sites of the hydrolysis); this cluster is only partially overlapped with one of the four MBP clusters. Anti‐H1 antibodies hydrolyze H1 at five sites of one cluster of the protein when anti‐MBP IgGs cleavage this histone at two clusters containing 17 sites of the cleavage. Anti‐H1 and anti‐MBP abzymes are the first examples of Abs possessing not only with cross‐complexing but also with catalytic cross‐reactivity. The existence of cross‐reactivity of abzymes against histones and MBP represent great danger to humans. © 2018 BioFactors, 45(2):211–222, 2019

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.…”

Natural Catalytic IgGs Hydrolyzing Histones in Schizophrenia: Are They the Link between Humoral Immunity and Inflammation?

“…The literature describes the widespread phenomenon of cross-complexing certain antibodies and enzymes with foreign ligands-antigens [ 32 , 33 , 34 , 46 ]. At the same time, cross-catalysis in the case of canonical enzymes is an extremely rare occurrence [ 47 ]. It was shown that abzymes against any specific protein usually hydrolyze only this, but no other control proteins [ 30 , 31 , 32 , 33 , 34 ].…”

“…It was shown that abzymes against any specific protein usually hydrolyze only this, but no other control proteins [ 30 , 31 , 32 , 33 , 34 ]. The first examples of cross-catalytic activity of antibodies have been discovered recently [ 41 , 47 ]. It has been shown that IgG antibodies against human histones effectively hydrolyze myelin basic protein (MBP) and, conversely, antibodies against MBP cleave histones [ 41 , 47 ].…”

“…The first examples of cross-catalytic activity of antibodies have been discovered recently [ 41 , 47 ]. It has been shown that IgG antibodies against human histones effectively hydrolyze myelin basic protein (MBP) and, conversely, antibodies against MBP cleave histones [ 41 , 47 ]. Therefore, catalytic cross-reactive antibodies against histones and MBP can play a negative role, contributing to the development of the disease [ 47 ].…”

“…It has been shown that IgG antibodies against human histones effectively hydrolyze myelin basic protein (MBP) and, conversely, antibodies against MBP cleave histones [ 41 , 47 ]. Therefore, catalytic cross-reactive antibodies against histones and MBP can play a negative role, contributing to the development of the disease [ 47 ]. Recently, we detected catalytic antibodies in serum of patients with schizophrenia that hydrolyze MBP [ 48 ].…”