Antibodies to gangliosides in coeliac disease with neurological manifestations

Abstract

Sirs, The authors thank Dr Volta et al. for their interest in our article on ‘Antiganglioside antibodies in children with celiac disease’,1 and for calling attention to their interesting data on adult coeliac disease (CD) patients with and without neurological manifestations. The authors find antibodies to GM1 and GD1b gangliosides in 36% of CD patients with neurological manifestations compared with 10% of CD patients without neurological symptoms. Although the difference is not significant, it points to a greater level of autoimmunity to neuronal antigens in CD patients with neurological manifestations. Different biological and immunological characteristics in childhood and adulthood, make it difficult to compare our findings in CD children to those reported in adults, as was discussed in our paper.1 Children express higher IgM antiganglioside antibody levels in the absence of neurological symptoms, whereas some CD adults with neuropathy have IgG antibodies to gangliosides.2 It would be interesting to know the antibody isotype for the CD patients described by Dr Volta et al. The different isotype may, in fact, reflect a different function of the antibodies (expression of innate repertoire in children, possible T cell-mediated mechanism of pathogenicity in adults), thus explaining the absence or presence of neurological involvement. The authors agree with Dr Volta et al. that the difference between the two studies might be ascribed to the well-known higher prevalence of neurological complications in adult, although it is still unclear whether this is a consequence of a longer exposure to gluten. We are currently prospectively following 42 adults with CD (32 female, 10 males, median age 36.3 ± 12 years), four of whom (9.5%) have clinical and neurophysiological evidence of mild, often subclinical, neuropathy.3 However, antiganglioside antibodies are not present in this population. It is possible that a more severe nerve damage is required before the antiganglioside antibodies are generated as a secondary response. Interestingly, three of the four patients with neuropathy have been on gluten-free diet for several years (11, 6, and 2, respectively), thus likely excluding a direct role of gluten in nerve damage. On the contrary, five of the 42 patients had antiganglioside antibody titres in the absence of neurological symptoms or signs. A follow-up evaluation after a median period of 9 months of both neurophysiological and humoral parameters did not show any significant difference. Hopefully, a large-scale prospective study might help to define the role, if any, of the antibodies to neuronal antigens in the neurological complications of CD.