IMMUNOLOGICAL MECHANISMS IN PROXIMAL DIABETIC NEUROPATHY

It has recently been proposed that proximal diabetic neuropathy (PDN) is an immune-mediated cindition which may improve following immunotherapy. We disigned a controlled, comparative, study of immunomodulation (human immunoglobulin) vs. immunosuppression (pronison with azathioprine) in a group of individuals with PDN. To avoid heterogenicity of the study group, we decided to include only those with classic, abrupt-onset form of PDN. Ten NIDDM patients have been enrolled in the study so far (age 65.4 ą 7.2 yrs, diabetes duration 10.2 ą 7.2 yrs, neuropathy duration 4.2 ą 1.7 mo, HbA1c 7.7 ą 1.3 %, femoral nerve conduction velocity 39.9 ą 8.4 m/s). One distal (sural) and one proximal nerve (intermediate cutaneous nerve of the tigh, ICNT) were surgically taken for histopathology, morphometry and immunopathology, before randomisation. The number of myelinated fibers was reduced in bothe the sural nerve (2756 ą 1436, p=0.0009) and ICNT (3104 ą 573, p=0.0004), as compared to a group of 11 control sural nerves (6561 ą 1152). Light microscopy revealed perivasculitis in the ICNT in one patient. No sural nerve had signs of immune cell infiltration. Other immunopathology findings re shown in the table. Axonal Ab Perineurial Ab Both Abs C3 Sural 2 3 3 3 ICNT 5 1 1 - Control - - - - Both, immunoglobulin M (IgM) and G were seen in the axons and perineurium, IgM being more prevalent. No clear correlation was found between various immunopathologic patterns and morphometric or neurphysiologic parameters. This study indicates a role of immunologic meshanisms in the pathogenesis of PDN. It seems that the humoral immune system effectors are more important in the process of nerve damage then the cellular.