Abstract: PO2410
The Role and Inducers of Nonclassical HLA-G in Renal Transplanted Allografts
Session Information
- Clinical and Immunologic Predictors of Post-Transplant Outcomes
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Kumano, Sho, Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan., Kahokugun, Japan
- Fujimoto, Keiji, Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan., Kahokugun, Japan
- Adachi, Hiroki, Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan., Kahokugun, Japan
- Furuichi, Kengo, Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan., Kahokugun, Japan
- Yokoyama, Hitoshi, Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan., Kahokugun, Japan
Background
Non-classical class I molecule HLA-G has a high potential to modulate immune response. However, the mechanism of HLA-G induction was still unknown. In this study, the expression of HLA-G on proximal tubular epithelial cells (pTECs) and the inducer of HLA-G were investigated.
Methods
Our subjects comprised 40 adult Japanese subjects whose allograft had survived for at least 1 year (35 patients from a living donor, 5 patients from a deceased donor). They were evaluated for HLA-G1/5 expression using an immunofluorescence method. We investigated inducer of HLA-G using primary cultured human pTECs treated with cytokines and immunosuppressants.
Results
In renal biopsy tissues, 2 to 4 weeks or 1 year following the transplantation, HLA-G expression was noted in the perinuclear region or on the basement membrane side of pTECs in 12 of 40 cases (30 %). Further, for median 8.8 years, the time taken for a 30 % reduction in eGFR was longer in the HLA-G-positive group than in the HLA-G-negative group (p=0.016, Figure). HLA-G1/5 expression on pTECs was also found to be an independent predictor of the improvement in renal allograft function by Cox’s proportional hazard model (p=0.030). In vitro study, interferon-beta (IFN-β) was the strongest inducer of HLA-G expression, while immunosuppressants (everolimus, tacrolimus, cyclosporin, and dexamethasone) did not induce expression.
Conclusion
The study showed that HLA-G1/5 expression on pTECs was an independent improving predictor of renal allografts. Furthermore, the strongest HLA-G1/5 inducer was IFN-β, but not the immunosuppressive agents. These results suggested the possibility that acquired expression of HLA-G exhibits a long-term renal preservation effect, different from the effect of immunosuppressants.