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P164 HLA G expression is differentially expressed in infiltrating cells in inflammatory bowel disease and in healthy specimens

S. Ferreira1, I. Abiodoun Sadissou2, R. Serafim Parra3, M. Ribeiro Feitosa3, F. Sanches Lizarte Neto4, D. Pretti da Cunha Tirapelli4, L. Naiara zambelli Ramalho5, O. Feres3, J.J. Ribeiro da Rocha3, E.A. Donadi2, L.E. de Almeida Troncon1

1Division of Gastroenterology, Department of Medicine- Ribeirão Preto Medical School- University of São Paulo, Ribeirao Preto, Brazil, 2Division of Clinical Immunology, Department of Medicine- Ribeirão Preto Medical School- University of São Paulo, Ribeirão Preto, Brazil, 3Division of Coloproctology, Department of Surgery and Anatomy, Ribeirão Preto, Brazil, 4Molecular Biology Laboratory, Department of Surgery and Anatomy, Ribeirão Preto, Brazil, 5Pathology, Department of Pathology- Ribeirão Preto Medical School- University of São Paulo, Ribeirão Preto, Brazil

Background

Since HLA-G is an immune checkpoint molecule and since Crohn’s disease (CD) and ulcerative colitis (UC) exhibit immune-mediated mechanism deregulation, we aimed to evaluate HLA-G intestinal expression and soluble (sHLA-G) levels in CD/UC patients, stratified according to CD phenotype/localisation and UC extension.

Methods

HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and 24 healthy controls, and in surgical resections (28 CD, 12 UC). Plasma sHLA-G levels (97 CD, 81 UC and 120 controls) were evaluated using ELISA

Results

HLA-G expression was observed in intestinal epithelial cells of controls and CD/UC specimens, exhibiting closely similar profiles, and in lamina propria infiltrating cells, exhibiting differential patterns. In biopsies, CD/UC lamina propria plasma cells/lymphocytes presented: i) increased HLA-G expression compared with controls (p < 0.0001), ii) irrespective of the extent, UC cell staining was greater compared with CD cells (p = 0.0011), and iii) the inflammatory CD phenotype presented increased number of infiltrating cells compared with stenosing and fistulizing phenotypes (p = 0.0407). In surgical resections, CD/UC patients exhibited increased infiltrating cell HLA-G expression in lesion areas compared with margins. sHLA-G levels were increased in UC/CD patients (p < 0.0001) when compared with controls, but no difference was observed between patients.

Conclusion

Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect host on-going strategies to suppress chronic inflammation.

References:

Renan Garcia Gomes, Carlos Alexandre Antunes de Brito et al, (2018), HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn’s disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression, Human Immunology, 79(6):477–484. doi: 10.1016/j.humimm.2018.03.006