Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

Tristetraprolin prevents gastric metaplasia in mice by suppressing pathogenic inflammation

Aberrant immune activation is associated with numerous inflammatory and autoimmune diseases and contributes to cancer development and progression. Within the stomach, inflammation drives a well-established sequence from gastritis to metaplasia, eventually resulting in adenocarcinoma. Unfortunately, the processes that regulate gastric inflammation and prevent carcinogenesis remain unknown. Tristetraprolin (TTP) is an RNA-binding protein that promotes the turnover of numerous pro-inflammatory and oncogenic mRNAs. Here, we utilized a TTP-overexpressing model, the TTPΔARE mouse, to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). We found that TTPΔARE mice were completely protected from ADX-induced gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression of Tnf, a well-known TTP target. Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.