Immunophenotyping of Granzyme-B Expressing Lymphocyte Subset in Renal Allograft Recipients with Chronic Allograft Dysfunction

Granzyme-B is a serine proteinase expressed and released mainly by the cytotoxic T and NK cell. Granules intact Granzyme-B is directly delivered into the target cell, while extracellular Granzyme-B, released in serum leads to nonspecific cleavages of extracellular matrix molecules like vitronectin, collagen, TGF-β, IL-1 and invites systemic inflammation, tissue remodeling and fibrosis leading to the development of chronic renal allograft dysfunction.

We aimed to immunophenotype the Granzyme-B positive T-lymphocyte subset and Granzyme- B role in the development of chronic renal allograft dysfunction.

We have analyzed the Granzyme-B+CD8+T/CD8neg and Granzyme-B+CD3+/CD3neg cell subset by the flowcytometry and serum Granzyme-B level by the enzyme-linked immunosorbent assay.

We have found that the frequency of Granzyme-B+ CD8neg CD3+T cell, Granzyme-B+ CD8lowCD3+T cell and Granzyme-B+ CD8high CD3+T cell subset was significantly lower and serum Granzyme-B level was significantly higher in CAD group. The frequency of CD3+T, CD3neg lymphocyte, CD8neg CD3+T, CD8lowCD3+T, CD8high CD3+T, Granzyme-B+CD3negCD8neg lymphocyte was similar between the group. The frequency of CD3+CD8negGzm-B+ cell was negatively correlated with serum creatinine and CD3+CD8highGzm-B+ cell was negatively correlated with serum Granzyme-B level. Similarly, Serum Granzyme-B level was positively correlated with serum creatinine, urine proteinuria and negatively with eGFR.

The circulating frequency of Granzyme-B+ CD8neg CD3+T cell, Granzyme-B+ CD8lowCD3+T cell and Granzyme-B+ CD8high CD3+T cell subsets were significantly lower and serum Granzyme-B level was significantly higher in renal allograft recipients with CAD.