Background: Since CD44 is involved in activation, proliferation, rolling and extravasation of lymphocytes, we hypothesized that it could be involved in the pathophysiology of acute renal allograft rejection.
Methods: Plasma and peripheral blood mononuclear cells (PBMCs) were collected from patients 24 h prior to transplantation and analysed retrospectively. Soluble CD44, interleukin-2 receptor (IL-2R), intracellular adhesion molecule-1 (ICAM-1) and C-reactive protein (CRP) in plasma were determined by enzyme-linked immunosorbent assay (ELISA). Cellular CD44 expression on peripheral lymphocytes was determined by flow cytometric analysis.
Results: Patients who later developed renal allograft rejection had statistically significantly increased soluble CD44 levels, but not soluble ICAM-1, IL-2R or CRP in plasma prior to transplantation. In addition, cellular CD44 on T-lymphocytes was decreased 24 h prior to transplantation in patients that would reject their allograft, compared with patients without rejection. Additionally, plasma CD44 and cellular CD44 revealed an inversely proportional correlation. Lipopolysaccharide (LPS)-induced immune activation did not influence plasma or cellular CD44 levels in healthy volunteers, suggesting that more specific factors influence the shedding of CD44 on T lymphocytes, leading to increased risk of renal allograft rejection.
Conclusion: Although the exact mechanism remains to be elucidated and further research is required, soluble CD44 levels and cellular surface CD44 on T lymphocytes prior to transplantation might be useful as predictive markers for the occurrence of acute renal rejection.