Distinct immunoglobulin class and immunoglobulin G subclass patterns against ganglioside GQ1b in Miller Fisher syndrome following different types of infection

Abstract

We studied serum antibodies against gangliosides GQ1b and GM1 in 13 patients with Miller Fisher syndrome (MFS) and in 18 patients with Guillain-Barré syndrome (GBS) with cranial nerve involvement. Anti-GQ1b titers were elevated in all patients with MFS cases (immunoglobulin G [IgG] > IgA, IgM), and in 8 of the 18 with GBS. Lower frequencies of increased anti-GM1 titers were observed in MFS patients (3 of 13), as well as in GBS patients (5 of 18). During the course of MFS, anti-GQ1b titers of all Ig classes decreased within 3 weeks after onset. By contrast, anti-GM1 titers (mainly IgM) transiently increased during the course of MFS in five of six patients, suggesting a nonspecific secondary immune response. In patients with MFS following respiratory infections, IgG was the major anti-GQ1b Ig class (six of six patients) and IgG3 was the major subclass (five of six). In contrast, four of five patients with MFS following gastrointestinal infections showed predominance of anti-GQ1b IgA or IgM over IgG and predominance of the IgG2 subclass; anti-GQ1b IgG (IgG3) prevailed in one patient only. These distinct Ig patterns strongly suggest that different infections may trigger different mechanisms of anti-GQ1b production, such as via T-cell-dependent as opposed to T-cell-independent pathways. Thus, the origin of antibodies against GQ1b in MFS may be determined by the type of infectious agent that precipitates the disease.

FIG. 1

IgA, IgG, and IgM anti-GQ1b titers (log₁₀ scale) in serum of 13 MFS patients, 18 GBS/cra patients, and 16 healthy controls (CON). Each point represents one individual (earliest serum sample available, 1:20 dilution). Broken lines indicate the cutoffs (mean ΔE plus 2 standard deviations of control group) for IgA, IgG, and IgM, respectively.

FIG. 2

Antibody titers against GQ1b and GM1 during the course of disease in sera of six MFS patients (A to F). Each point represents a sequential sample, diluted 1:20 and 1:10 for anti-GQ1b and anti-GM1, respectively. Titers of the IgA class (triangles), IgG class (circles), and IgM class (squares) are given as ΔE/cutoff ratios; values above the corresponding cutoff are given as solid symbols, and those below the cutoff as given as open symbols. Cases shown in panels A, B, C, D, E, and F correspond to patients 5, 13, 12, 2, 10, and 6, respectively (see Table 3). Arrows indicate the time points of treatment with intravenous Ig (B, C, D, and F) or plasmapheresis (A).