Treatment resistant autoimmune autonomic ganglionitis associated with increased serum immunoglobulin light chains

Abstract

Background & Objective: The mechanism of anti-ganglioside complex (GSC) antibody phenomenon in Guillain–Barre syndrome (GBS) is not revealed yet. In most case, one of the two gangliosides forming GSC is GM1, GD1b, or asialo-GM1 (GA1), which contains common neutral oligosaccharide structure, Gal(beta1-3)GalNAc, in non-reducing terminal, and patients shows clinical features of antibody against the other ganglioside. This suggests a possibility that the neutral oligosaccharide structure changes accessibility or affinity of the antibody to the pendant, not forming a novel conformational epitope. We studied the effect of the neutral oligosaccharide structure to the anti-GSC. Methods: Sera from patients with GBS or Fisher syndrome with antibodies against GSCs composed of GA1 and one of GD1a, GD1b, and GQ1b were studied on the effect of the replacement of GA1 in the GSCs with other neutral glycolipids or lipidwith partial common structure. Antibody titers were measured by enzyme-linked immunosorbent assay (ELISA). The neutral glycolipids and lipid examined were following: asialoGM2(GA2), globoside, trihexosylceramide, paragloboside, glucosaminyl lactosylceramide, lactosylceramide, glucosylceramide and ceramide. Results: Four of 11 GA1/GD1a antibody-positive cases and four of 11 GA1/ GD1b antibody-positive cases also showed an enhancement of the antibody reaction by mixing with other neutral glycolipids instead of GA1. In these cases, the degree of the enhancementwasweaker compared to mixing with GA1. Nine of 16 GA1/GQ1b antibody-positive cases, also showed an enhancement of the antibody reaction by mixing with other neutral glycolipids. In five of them, the degree of the enhancement was equal or stronger than in GA1/GQ1b complex. Twelve cases showed enhancement bymixingwith ceramide. In these cases, ELISAwith reduced amount of the single ganglioside, which had been mixed with ceramide, showed decrement of the titer in seven cases and increment in three. Conclusions: There would be non-conformational, i.e. structure-nondependent, mechanism in enhancement of antigen–antibody reaction by mixing two gangliosides, as well as structure-dependent one. In the cases who showed enhanced reaction by reducing the quantity of ganglioside antigen, it is possibly considered that accessibility of antibody to antigen has improved by reduction of antigen density. One of the gangliosides in GSC might act as spacer separating true antigenic epitope in some cases.