Transglutaminase 2-specific coeliac disease autoantibodies induce morphological changes and signs of inflammation in the small-bowel mucosa of mice.
Amino Acids
; 49(3): 529-540, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27503559
ABSTRACT
Coeliac disease is hallmarked by an abnormal immune reaction against ingested wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2 (TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of the disorder develops gradually from normal villus morphology to inflammation and finally to villus atrophy with crypt hyperplasia. Patients with early-stage coeliac disease have TG2-autoantibodies present in serum and small-intestinal mucosa and they may already suffer from abdominal symptoms before the development of villus atrophy. Previously, we have shown that intraperitoneal injections of coeliac patient-derived sera or purified immunoglobulin fraction into mice induce a condition mimicking early-stage coeliac disease. In the current study, we sought to establish whether recombinantly produced patient-derived TG2-targeted autoantibodies are by themselves sufficient for the development of such an experimentally induced condition in immune-compromised mice. Interestingly, mice injected with coeliac patient TG2-antibodies had altered small-intestinal mucosal morphology, increased lamina propria cellular infiltration and disease-specific autoantibodies deposited in the small bowel, but did not evince clinical features of the disease. Thus, coeliac patient-derived TG2-specific autoantibodies seem to be sufficient for the induction of subtle small-bowel mucosal alterations in mice, but the development of clinical features probably requires additional factors such as other antibody populations relevant in coeliac disease.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
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Enfermedad Celíaca
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Transglutaminasas
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Huésped Inmunocomprometido
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Proteínas de Unión al GTP
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Mucosa Intestinal
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Intestino Delgado
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Anticuerpos Monoclonales
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Amino Acids
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Finlandia