Small-intestinal TG2-specific plasma cells at different stages of coeliac disease

BMC Immunology

Teea Salmi¹  Katri Kaukinen¹  Outi Koskinen¹  Tuire Ilus¹  Katri Lindfors¹  Kaija Laurila¹  Minna Hietikko¹  Päivi Saavalainen²  Heini Huhtala³  Kalle Kurppa⁴ 

[1] Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere;Department of Medical and Clinical Genetics and the Research Programs Unit, Immunobiology, University of Helsinki;Faculty of Social Sciences, University of Tampere;Tampere Center for Child Health Research, University of Tampere;

关键词: Coeliac disease;    Gluten;    Transglutaminase 2;    Autoantibody;    Small intestine;   

DOI  :  10.1186/s12865-018-0275-7

来源: DOAJ

【 摘 要 】

Abstract Background In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes. Results Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (rS = 0.69, P < 0.001) and the intensity of mucosal TG2-targeting IgA deposits (rS = 0.43, P < 0.001) was observed. Conclusions Our results show that TG2-specific plasma cells are already detectable prior to villous atrophy, and that generally their frequency increases during overt disease. By contrast, on GFD, the percentage of these cells decreases. Overall, the presence of TG2-specific plasma cells in the small bowel mucosa mirrors the presence of gluten in the diet, but the frequency is not always parallel to the level of serum or intestinal TG2 antibodies. These findings increase the knowledge about the development of the TG2 plasma cell responses especially in the early phases of coeliac disease.

【 授权许可】

Unknown