Trapped immunoglobulins on peripheral nerve myelin from patients with diabetes mellitus.
Diabetic peripheral neuropathy is characterized by endoneurial capillary closure and by segmental demyelination and axonal degeneration in a spatial pattern consistent with ischemic damage. The increased permeability of human diabetic endoneurial capillaries to plasma proteins may contribute to the pathogenesis of these structural changes in peripheral nerve by further accelerating the rate at which plasma proteins are trapped by reactive nonenzymatic glycosylation products on long-lived proteins such as myelin. We have measured trapped immunoglobins (Ig) G and M on peripheral nerve myelin from diabetic and nondiabetic patients by an enzyme-linked immunosorbent assay to determine whether plasma proteins accumulate on nerves as they do in the glomerular matrix of diabetics. The amount of trapped IgG on brain myelin from these subjects was also determined. Peripheral nerve myelin from diabetics had on average greater than 14 times the amount of trapped IgM found in identically prepared samples from nondiabetics (0.90 +/- 0.2 vs. 0.06 +/- 0.004 OD/micrograms myelin protein) and greater than 4 times the amount of trapped IgG (6.40 +/- 1.92 vs. 1.5 +/- 0.25 OD/micrograms myelin protein). In contrast, no significant trapping of IgG was detected in any samples of brain myelin. This most likely reflects effective exclusion of IgG by the blood-brain barrier. These data suggest that excessive trapping of Igs and other plasma proteins by diabetic peripheral nerve myelin may contribute to the development of peripheral nerve damage, whereas the lack of such trapping by brain myelin may partly explain the rarity of diabetic central neuropathy.
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins