Novel immune response to gluten in individuals with schizophrenia.
Samaroo D, Dickerson F, Kasarda DD, Green PH, Briani C, Yolken RH, Alaedini A.
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, United States.
A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.
PMID: 19748229 Sept 2009
I'm happy to see this study coming out of Cornell.
Instead of just completely dismissing gluten sensitivity in those with schizophrenia because they don't neccesarily show celiac disease markers (anti-tTG2, deamidated gliadin, and HLA DQ2 or HLA DQ8)... it suggests more study is needed.
We have learned that gluten ataxia can be indepedent of celiac markers via the work of Dr. Marios Hadjivassiliou. I look forward to more meaningful research in regard to to gluten and schizophrenia.
However, the mechanism of the
observed antibody reactivity to gluten in schizophrenia appears
to be fundamentally different from celiac disease. As such, the
heightened immune response to gluten deserves further
attention and research in determining its importance and
relevance to the pathogenesis of schizophrenia, independent of
concomitant celiac disease. Further detailed characterization of
the antibody response to gluten and other dietary proteins of
concern, including casein, is likely to enhance our understanding
of the significance of the immune system and its response to
foreign antigens in schizophrenia and other neuropsychiatric
abnormalities. The elucidation of this relationship may lead to
new methods for the diagnosis, prevention, and treatment of
schizophrenia and related disorders.
Samaroo, D., et al., Novel immune response to gluten in individuals with schizophrenia, Schizophr.
Res. (2009), doi:10.1016/j.schres.2009.08.009
Other studies can be found in The Gluten File here: