Anti-GM1 antibodies as a model of the immune response to self-glycans

NORES GA; LARDONE RD; COMIN R; ALANIZ ME; MOYANO AL; IRAZOQUI FJ

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

Elsevier

Año: 2008 vol. 1780 p. 538 - 545

0304-4165

Glycans are potentially high variable molecules, frequently found in the plasma membrane facing the extracellular space. These characteristics lead to consider glycans as putative recognizing molecules involved in the social events of the cells but also as target of pathological factors causing diseases. The induction of anti-glycan antibodies is one of early events in the defence toward bacterium that colonize the body. As a consequence of this natural infection, antibodies recognizing a variety of bacteria glycans are found in adult sera of human and animals. The immune response to glycans is restricted by self-tolerance and normally no antibodies to self-glycans should exist. Nevertheless antibodies recognizing structures close related to self-glycans exist and can be the source of harmful anti-self antibodies. Normal human serum contains low affinity anti-GM1 antibodies IgM-antibodies. Similar antibodies with higher affinities or different isotype are found in some neuropathy patient. Two hypotheses have been developed to explain the origin of disease associated anti-GM1 antibodies. The “molecular mimicry” hypothesis proposes the mimicry between GM1 and Campylobacter jejuni lipopolysaccharide carrying a GM1-like glycan as the cause of Guillain-Barré syndrome associated to anti-GM1 IgG-antibodies. The “binding site drift” hypothesis places the origin of IgM-antibodies associated to disease in changes in the binding site of normally occurring anti-GM1 antibodies. An “integrated” hypothesis, considering both proposals, can explain most of the data about anti-GM1 antibodies that have been published.