Neurology -- Correspondence for Bushara et al., 62 (1) 132-133

Correspondence published:

Reply to Barta et al: K.O. Bushara (11 February 2004)

Antigliadin antibodies in Huntington’s disease: Zsolt Barta, Gabriella Mekkel and Margit Zeher (11 February 2004)

Reply to Barta et al 11 February 2004

K.O. Bushara,
Minneapolis VA Medical Center
(127) Minneapolis VAMC, One Veterans Drive, Minneapolis, MN 55417
Send Correspondence to journal:
Re: Reply to Barta et al

busha001{at}umn.edu K.O. Bushara

We thank Barta et al for their comments. Whether the increased expression of tissue transglutaminase (tTG) shown in degenerative diseases (Alzheimer’s disease, HD and other polyglutamine diseases) leads to the development of anti-tTG antibodies is still unclear. However, from our prior study in ataxia patients, anti-tTG antibodies were positive in only a minority of patients with high anti-gliadin antibodies. [4]
References
4. Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M. Gluten sensitivity in sporadic and hereditary cerebellar ataxia. Ann Neurol 2001;49:540-3.

Antigliadin antibodies in Huntington’s disease 11 February 2004

Zsolt Barta,
3rd Department of Medicine, University of Debrecen
Moricz Zs. krt. 22, Debrecen, Hungary,
Gabriella Mekkel and Margit Zeher
Send Correspondence to journal:
Re: Antigliadin antibodies in Huntington’s disease

barta{at}iiibel.dote.hu Zsolt Barta, et al.

We read with interest the article by Bushara et al on antigliadin antibodies in Huntington's disease (HD). [1] The authors report high antigliadin antibody titers in 44% patients with HD, suggesting a previously unrecognized association between HD and gluten sensitivity. Tissue transglutaminase (tTG) antibodies assay and duodenal biopsies were not performed.
The tTG antibodies should be considered. Gluten sensitive diseases (dermatitis herpetiformis and celiac disease) have common immunopathological and genetic mechanisms. Celiac disease (CD) is a complex autoimmune disease characterized by a strong genetic association with gluten as a nutritional etiological factor and the enzyme tissue transglutaminase as an endomysial autoantigen. Patients develop highly predictive IgA autoantibodies to tTG. Increased intestinal expression of tTG in patients with CD may play an important role in the pathogenesis of CD. Modification of gluten peptides by tTG, especially deamidation of certain glutamine residues, can enhance their binding to HLA-DQ2 or -DQ8 and potentiate T cell stimulation. tTG-catalyzed cross- linking and consequent haptenization of gluten with extracellular matrix proteins allows for storage and extended availability of gluten in the mucosa. [1]
tTG likely also contributes to numerous processes in the nervous system. HD is a genetic disorder caused by an expansion of the polyglutamine domain in the huntingtin protein. Because a polypeptide bound glutamine is the determining factor for a tTG substrate (polyamination of proteins is likely to effect their function), and mutant huntingtin aggregates have been found in Huntington's diseased brains, it has been hypothesized that tTG may contribute to the pathogenesis of Huntington's disease by modifying specific proteins and altering their function or localization. [2] Based on these findings,modulation of transglutaminase activity could be explored as a treatment for HD. [3] We think that tTG antibody determination in patients with HD may enrich the authors’ observations.
References
1. Dieterich W, Esslinger B, Schuppan D. Pathomechanisms in celiac disease. Int Arch Allergy Immunol 2003; 132(2):98-108.
2. Lesort M, Chun W, Tucholski J, Johnson GV. Does tissue transglutaminase play a role in Huntington's disease? Neurochem Int 2002; 40(1):37-52.
3. Zainelli GM, Ross CA, Troncoso JC, Muma NA. Transglutaminase cross-links in intranuclear inclusions in Huntington disease. J Neuropathol Exp Neurol 2003; 62(1):14-24.