IgA Antibodies Against Gliadin and Tissue Transglutaminase in Dogs With Chronic Enteritis and Intestinal T-Cell Lymphoma

Abstract

Molecular clonality analysis of T-cell receptor (TCR) genes for diagnosing T-cell lymphoma is widely used in veterinary medicine. However, differentiating chronic enteritis (CE) from intestinal lymphoma is challenging because of the incompatibility between histopathologic and clonality analysis results. On the basis of findings that canine intestinal T-cell lymphoma and celiac disease share some common features, we conducted serologic examinations in combination with histopathologic and T-cell receptor clonality analyses in 48 dogs diagnosed with either CE or intestinal lymphoma. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against gliadin and tissue transglutaminase (tTG) were quantitatively measured using ELISA. The conditions were classified according to the histopathologic diagnosis, clonality analysis, and combined histopathologic/clonality analysis. Histopathologic analysis showed that dogs with intestinal lymphoma were likely to have high levels of serum IgA antibodies against gliadin and tTG, and serum IgG antibodies against tTG. No correlation between the diagnosed groups and control group was observed in the results of the clonality analysis and histopathologic/clonality analysis. It is interesting that dogs with intestinal lymphoma had a higher serum IgA titer against gliadin and tTG than did dogs with CE. These results suggest an association between repetitive inflammatory stimulation by gliadin peptides and subsequent intestinal lymphoma in dogs.

Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease

“…In humans, the presence of anti‐gliadin titers has been generally associated with food sensitivity to ingredients containing these highly immunogenic proteins causing different degrees of pathophysiology ranging from GI discomfort to celiac disease 38 . Previous studies have shown the presence of anti‐gliadin antibodies in the sera of dogs with chronic enteritis 39 using Western Blot analysis and intestinal T‐cell lymphoma 40 both by Western and ELISA, and also in dogs diagnosed with paroxysmal‐gluten sensitivity dyskinesia 41 . In our study we report that a significant proportion of dogs suffering GI conditions present with high titers of anti‐gliadin IgA antibodies in a statistical differential manner to asymptomatic (normal) dogs highlighting the potential value of gliadin seropositivity as indicator for canine GI conditions when use in combination with other relevant markers.…”

Pathological features of intestinal T‐cell lymphoma in Shiba dogs in Japan

“…Haematoxylin and eosin‐stained sections were evaluated and utilized for diagnosis by consensus between 2 veterinary pathologists. Lymphoma composed of cells with nuclei smaller than 2 red blood cells in diameter was defined as small cell lymphoma (SCL), and that with nuclei larger than 2 red blood cells in diameter was defined as large cell lymphoma (LCL), consistent with previously reported diagnostic criteria . Immunohistochemistry (IHC) was performed using a panel of antibodies including CD3 (Dako Japan, Tokyo, Japan), CD79 (Dako Japan), CD20 (Thermo Fisher Scientific, Waltham, Massachusetts), CD56 (LifeSpan BioSciences, Seattle, Washington) and granzyme B (Spring Bioscience, Pleasanton, California) on duodenal and ileal tissue specimens.…”

“…PCR for antigen receptor gene rearrangement (PARR) was conducted as described in previous studies . Briefly, tissue samples were endoscopically collected from the duodenum and ileum and stored at −20°C until use.…”

“…Histopathologic and immunohistochemical analyses were performed as described in a previous study . Briefly, endoscopic tissue samples were collected from the stomach, proximal duodenum, distal duodenum, ileum and colon.…”

“…PCR for antigen receptor gene rearrangement (PARR) was conducted as described in previous studies. 6,7 Briefly, tissue samples were endoscopically collected from the duodenum and ileum and stored at −20 C until use. Genomic DNA was extracted from frozen samples by using the DNeasy Blood and Tissue Kit (Qiagen, Valencia, California).…”