Impaired immune defense in hemodialysis patients: Role of alpha-defensins?

Abstract

The mechanisms underlying the impaired immune response in hemodialysis (HD) patients are not completely understood. The alpha-defensins human neutrophil peptides-1, 2, and 3 are low molecular weight peptides with antimicrobial activity and important effector molecules of innate immune responses. We now examined the expression of these peptides in HD patients. Seventy-six patients on chronic HD treatment (mean time on HD 5.8 years; mean age 70 years) were studied and compared with 38 healthy volunteers and 20 patients with infections and normal renal function. Expression of alpha-defensins was analyzed semiquantitatively in leukocytes on the messenger RNA (mRNA) level by reverse transcriptase polymerase chain reaction; the alpha-defensin protein levels in serum were detected by enzyme-linked immunosorbent assay. alpha-Defensin concentrations (140 +/- 10.5 ng/mL; mean +/- standard error of the mean) as well as mRNA levels in leukocytes (82.9 +/- 7.9 arbitrary units [a.u.]) in HD patients were not significantly different from those in healthy volunteers (156 +/- 15.2 ng/mL; 81.4 +/- 11.3 a.u.). Defensin levels were independent of the time of the patient on HD and their age. During infection periods (mean increase of the C-reactive protein to 161 +/- 17.3 mg/L), defensin serum levels increased to 321 +/- 65 ng/mL (P < 0.005) and mRNA expression in leukocytes to 159 +/- 19.2 a.u. (P < 0.05). These increases were not significantly different from those in patients with normal renal function (298 +/- 46.8 ng/mL and 128 +/- 9.1 a.u., respectively) suffering from infections (C-reactive protein 222 +/- 26.6 mg/L). Our results suggest that the impaired immune defense in dialysis patients is not due to a deficiency in alpha-defensins in these patients as neither basal levels nor expression during infections were reduced compared with subjects with normal renal function.