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Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
Expression of HLA-G and MICA mRNA in renal allograft
Andrea L Racca1, Carolina M Veaute, Alejandra S Bailat
1Laboratorio de Inmunología Básica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Pje El Pozo, Santa Fe, Argentina.
Abstract:
HLA-G is a nonclassical MHC class I antigen that displays tolerogenic functions; MICA is a stress-regulated molecule recognized by NKG2D cytotoxicity-activating receptor expressed by NK and T cells subsets. We evaluated HLA-G isoforms and MICA mRNA levels in peripheral blood mononuclear cells (PBMCs) and in biopsies from kidney allograft recipients with acute rejection (AR), chronic rejection (CR), and stable graft evolution (SE). HLA-G1 was the only transcript resulted from amplification, both in PBMCs as in biopsy samples. HLA-G1 mRNA levels in PBMCs from 9/10 patients with CR, 7/9 with AR and 8/10 healthy volunteers were below the median value of SE patients. The analysis of biopsies revealed that patients with AR (n=6), who overcame rejection had a tendency towards higher HLA-G1 levels than those with nephrotoxic acute tubular necrosis (ATN) (n=3). Similar levels of MICA expression were observed in PBMCs from AR, CR, SE and C groups; MICA expression levels were similar also in biopsy specimens from AR and nephrotoxic ATN patients. No correlation was found between MICA expression and the graft state. These preliminary results suggest that HLA-G1 isoforms, but not MICA mRNA levels, may provide a marker for measuring the state of kidney allograft, and be the basis for further studies that may establish the influence of these molecules in renal allograft rejection or acceptance.
Insights
Human Leukocyte Antigen-G (HLA-G) expression may indicate kidney transplant health. Lower HLA-G1 mRNA levels in patients suggest potential rejection, unlike MICA, which showed no correlation with graft status.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Molecular diagnostics
Background:
- Human Leukocyte Antigen-G (HLA-G) is a nonclassical MHC class I antigen with tolerogenic functions.
- MICA is a stress-regulated molecule recognized by the NKG2D receptor, activating NK and T cell cytotoxicity.
- Kidney allograft recipients experience acute rejection (AR), chronic rejection (CR), or stable graft evolution (SE).
Purpose of the Study:
- To evaluate HLA-G isoforms and MICA mRNA levels in kidney allograft recipients.
- To determine if these molecules correlate with AR, CR, or SE.
- To assess their potential as biomarkers for kidney transplant status.
Main Methods:
- Analysis of HLA-G and MICA mRNA levels in peripheral blood mononuclear cells (PBMCs) and kidney allograft biopsies.
- Comparison of expression levels between patients with AR, CR, SE, and healthy controls.
- Assessment of MICA expression in relation to graft state.
Main Results:
- HLA-G1 was the only amplified HLA-G transcript in both PBMCs and biopsies.
- Lower HLA-G1 mRNA levels were observed in patients with CR and AR compared to stable graft recipients.
- Biopsy analysis showed a trend towards higher HLA-G1 levels in AR patients who recovered compared to those with acute tubular necrosis (ATN).
- MICA expression levels were similar across all groups (AR, CR, SE) and showed no correlation with graft status.
Conclusions:
- HLA-G1 isoforms, but not MICA mRNA levels, may serve as potential biomarkers for monitoring kidney allograft status.
- Further research is warranted to establish the role of HLA-G1 in renal allograft rejection and acceptance.
