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P263 Association between inflammatory bowel diseases and the non-classical histocompatibility complex HLA-G

S. da Costa Ferreira1, I. Abiodoun Sadissou2, R. Serafim Parra3, M. Ribeiro Feitosa3, F. Santos Lizarte Neto4, D. Pretti da Cunha Tirapelli4, L. Naira Zambelli Ramalho5, O. Féres3, E. Antônio 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 Medical School, University of São Paulo, Ribeirao Preto, Brazil, 4Molecular Biology Laboratory, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil, 5Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

Background

HLA-G is a non-classical major histocompatibility complex (HLA) class I molecule with immunomodulatory properties. Considering that inflammatory bowel diseases (IBD), represented mainly by Crohn's disease (CD) and ulcerative colitis (UC), have immune-mediated mechanisms in their pathogenesis, the aim of this study was to determine the association between soluble (s) HLA-G production and the HLA-G expression in patients with IBD in a tertiary IBD unit in Southeastern Brazil.

Methods

sHLA-G levels were measured with ELISA in plasma of IBD patients (n = 199; 54.4% female; mean age at diagnosis: 32.84 ± 13.37 years) and healthy controls (n = 120). Tissue expression of HLA-G was assessed by immunohistochemistry in samples of the colon and terminal ileum from 152 patients (91 CD; 62 UC) and 24 healthy controls. We evaluated sHLA-G levels and HLA-G expression in patients with IBD (CD and UC) when compared with healthy controls. We also determined the relationships between sHLA-G levels and tissue HLA-G expression and CD phenotype and localisation, and UC extension.

Results

There was a significant increase (p < 0.0001) in sHLA-G levels in IBD patients when compared with healthy controls (Figure 1).

Boxplot of serum sHLA-G concentrations in patients with IBD and in healthy controls.

There were no significant differences between CD and UC patients. No differences were observed between the various CD phenotypes and localisation patterns, neither between subgroups of UC patients with different disease extent. HLA-G was similarly expressed (p = 0.21) in the epithelial cells of the colon and terminal ileum in IBD patients (CD: 64.8%; UC: 70.5%) and in healthy controls (83.3%). Regarding inflammatory cells (plasma cells and lymphocytes), HLA-G was highly expressed in IBD intestinal tissue samples (CD: 73.3%; UC: 80.3%; p > 0.05), which was not found in any sample (0%) of healthy controls (p < 0.001). In CD, expression of HLA-G in tissue inflammatory cells was found more frequently in the inflammatory phenotype than in patients with stenosis (94.1% vs. 61.1%; p = 0.03). No differences were observed between the various CD localisation patterns, neither between subgroups of UC patients with different disease extent.

Conclusion

Higher levels of sHLA-G and increased tissue expression of HLA-G in patients with IBD suggest that this molecule may play a role in disease pathogenesis. Measurement of sHLA-G production may comprise a novel non-invasive diagnostic tool in IBD.1,2

References

1. Zidi I, Yahi HB, Bortolotti D, et al. Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn’s disease. Int Immunol 2014;27:289–96. doi:10.1093/intimm/dxv002

2. Gomes RG, Brito CAA, Martinelli VF, et al. 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. Hum Immunol 2018;79:477–84. doi:10.1016/j.humimm.2018.03.006