Phospholipid and Glutamic Acid Decarboxylase Autoantibodies in Diabetic Neuropathy

OBJECTIVE To determine the prevalence and significance of phospholipid autoantibodies (PLAs) and glutamic acid decarboxylase (GAD) autoantibodies in the circulation of normal patients and diabetic patients with and without neuropathy.

RESEARCH DESIGN AND METHODS We measured PLAs in a total of 78 patients (a diabetic group with somatic or autonomic neuropathy [n = 40] another group without neuropathy [n = 38]), and GAD autoantibodies in a subset of 22 patients.

RESULTS PLAs are found in 2% of the general population. We found PLAs in 32% of the diabetic population without neuropathy, in 88% of those with neuropathy, in 55% of those with retinopathy, and in 25% of those with established nephropathy. The frequencies of immunoglobulins in the neuropathic group were: IgG = 78%, IgM = 33%, and IgA = 23%. There was no correlation between PLAs and microalbuminuria, macrovascular disease, fibrinogen, duration of diabetes, or neuropathy, but there was a strong correlation with total neuropathy score. Sera with high PLA IgG titers bound to the surface of neuroblastoma cells and inhibited cell growth. Antibodies to GAD65 were present in 32% and to GAD67 in 0% of patients. No titers of GAD65, GAD67, or the GAD65 ratio were associated with the degree of neuropathy of the presence of PLAs.

CONCLUSIONS PLAs occur frequently in the sera of patients with diabetes and correlate with the extent of neuropathy, suggesting a role for PLAs in the etiology thereof. The measurement of PLAs may constitute a marker for ongoing damage to nerves.