N-glycoforms of serum alpha-1-acid glycoprotein in patients with lower limb chronic arterial ischaemia

Abstract

Alterations of serum acute phase proteins (APP) N-glycosylation are observed in various necrotic and inflammatory processes. In artherosclerotic chronic arterial ischaemia of the lower extremities, such alterations have not been reported. N-glycoforms of representative APP, alpha-1-acid glycoprotein (AGP), interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R), involved in regulation of APP N-glycosylation, were studied in 42 patients sera. Twelve patients had moderate, and 30 had critical ischaemia. In 35 patients reconstructive surgery, and in 7, amputation, was performed. In 16 patients following surgery complications were observed. AGP N-glycoforms were studied using crossed immuno-affino-electrophoresis with Concanavalin A before surgery, at days 1–3, and 7–12 following operation. Three AGP N-glycoforms were found: AGP-0, AGP-1 and AGP-2. In moderate ischaemia, shift towards AGP-0 was seen. In critical ischaemia, shift towards AGP-2 was observed. IL-6 levels were higher in critical than moderate ischaemia, while sIL-6R levels were similar. At days 1–3, shift of AGP N-glycoforms typical for acute infection was seen. At days 7–12, in uncomplicated cases, AGP N-glycosylation profiles returned to normal, while with complications, they stayed unchanged or continue to shift further. Assessment of AGP serum N-glycoforms may prove to be clinically useful in grading of chronic lower limb ischaemia and monitoring of patients undergoing surgery.