Antibodies against advanced glycation end product N-epsilon-(carboxymethyl)lysine in healthy controls and diabetic patients

Aims/hypothesis. N-epsilon-(carboxymethyl)lysine (CML) is one of the end pr oducts of protein glycoxidation and its accumulation is associated with dia betes complications. Since CML-modified proteins are immunogenic, we have i nvestigated the presence of anti-CML antibodies in diabetic patients. Methods. Antibodies against CML-modified human serum albumin (HSA) were mea sured by direct enzyme-linked immunosorbent assay in the sera from 289 non- selected diabetic and in 120 healthy control subjects. Results. Immunoglobulin-G reactivity towards CML-HSA was significantly high er in diabetic than in control sera. The presence of anti-CML IgG in diabet ics, however, was not influenced by age, duration of disease or glycaemic c ontrol. Analysis of distribution frequency revealed that anti-CML IgG in bo th control and diabetic subjects were not normally distributed and that the distribution curves were similar in the two groups. Moreover, only 14% of the diabetic subjects displayed antibody binding to CML-HSA above 95 centil e in the control cohort. Competition experiments confirmed that the IgG det ected in both control and diabetic groups were specific for CML epitopes an d did not recognise glycated-HSA in which CML formation was inhibited. Conclusion/interpretation. The presence of anti-CML IgG in diabetic sera is probably not related to the development of an immune response against prot ein glycoxidation products.