The humoral response in the pathogenesis of gluten ataxia

To the Editor:

Patients with sporadic ataxia (about 10%) have evidence of gluten sensitivity, a syndrome that is contingent on intolerance to dietary gluten.1 Intestinal manifestations result from an immunologically mediated process, while the pathogenesis of neurologic symptoms is not yet understood. As in celiac disease, the HLA DQB1*0201 haplotype is found in 70% of patients with gluten ataxia, suggesting that neurologic symptoms are likely to refer to similar pathomechanisms.

In their recent article Hadjivassiliou et al.2 report the critical role of circulating antibodies against Purkinje cells in gluten ataxia.2 However, pathologic studies have pointed to a cell-mediated immune response with loss of Purkinje cells and lymphocytic infiltration.3 The question to address is whether circulating antibodies account for cerebellar symptoms in gluten ataxia by testing patients’ sera for crossreactivity with CNS tissue. Cerebellar slices of Callithrix jacchus were stained with sera of 10 patients with gluten ataxia (mean age 53.4 ± 19.7), 6 patients with hereditary cerebellar ataxia, and 9 healthy controls. Patients were not under a gluten-free diet nor did they receive any immune-modulating therapy. Sera of patients with anti-Yo syndrome and anti-Hu syndrome served as positive controls for antineuronal reactivities.

All sera were tested at different dilutions with a BIOCHIP-mosaic containing primate cerebellum and liver as control tissue (Euroimmum, Germany). Fluorescently labeled anti-IgG or anti-IgA secondary antibodies were used as conjugates. This technique is characterized by staining specifications under controlled conditions with sensitivities comparable to immunocytochemical detection methods. Results were compared to staining sensitivities of positive controls on rat cerebellar slices using immunocytochemistry (peroxidase detection) applying the BIOCHIP immunofluorescence technique. Both techniques yielded comparable detection thresholds in anti-Hu and anti-Yo syndrome even at high dilutions, and the immunofluorescence technique provided higher specificity with more defined cellular and subcellular distribution of staining.

Whereas anti-IgG in …