Monoclonal antiidiotypic antibodies neutralize cytotoxic effects of anti-alphaGal antibodies.

The aims of this study were to produce and characterize mouse monoclonal antiidiotypic antibodies (AIAs) that specifically bind human antipig (anti-alphaGal) antibodies and to select those AIAs that neutralize the cytotoxicity of human or baboon serum to pig (PK15) cells. Mice were immunized with human anti-pig antibodies, and hybridomas were produced using conventional techniques. From a total of 480 clones, 11 produced AIAs that bound with high affinity to human anti-alpha Gal IgG and F(ab')2 fragments, and individually reduced serum cytotoxicity to pig cells by 40 - 90%. Seven of the AIAs also bound to human peripheral B lymphocytes (that express the same idiotypes as the antibodies produce). Several combinations of two or three AIAs provided 100% protection of PK15 cells. Selected AIAs injected intravenously into baboons reduced the cytotoxicity of subsequently drawn sera by 50--80% for >48 hr. The cytotoxicity studies also indicated that there are at least two dominant idiotypes expressed in the human anti-alphaGal population. We conclude that AIAs against anti-alphaGal antibodies could be successfully used in 1) preoperative characterization of a recipient's anti-alphaGal profile, (2) prevention of hyperacute rejection of a pig organ, and (3) specific immunosuppression through elimination of anti-alphaGal-producing B lymphocytes.

Non-cirrhotic and non-malignant acute extrahepatic portal vein thrombosis (PVT): short- and long-term results.

This observational cohort study reports the short- and long-term clinical outcomes of 31 patients admitted for acute non-malignant, non-cirrhotic portal vein thrombosis (PVT) over a 10-year period. Patients had a mean age of 43 years at admission and a mean duration of follow-up of 84 months. All patients were initially treated with anticoagulants. Complete recanalization occurred within 30 days after admission in 18 patients (58%), partially in nine patients (29%), and failed in four patients (13%). During follow-up, 10 patients (32%) had at least one episode of gastrointestinal bleeding. The probability of remaining bleed-free was 0.93 at 24 months and 0.61 at 48 months. Fundal varices were not controlled by endoscopic sclerotherapy, so all four patients underwent portosystemic shunt construction. To date, there has been no mortality. In conclusion, using a combination of different treatment options reduces the risk of death and late complications in patients with non-malignant, non-cirrhotic PVT.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in acute lower limb ischaemia.

For various reasons some patients are unable to undergo intra-arterial thrombolysis for acute limb ischaemia. This interventional case series study prospectively evaluated the effect of thrombolytic treatment with 100 mg recombinant tissue plasminogen activator (rt-PA), administered intravenously, in patients with acute thrombosis of the lower limb arteries and onset of symptoms within 12 h prior to treatment. During a 3-year period (2007-2009), 18 of 86 patients satisfied the inclusion criteria and were included in the study (age range 65-80 years; 11 women). Complete and partial thrombolysis was observed in eight (44.4%) and six (33.3%) patients, respectively. All patients experienced clinical improvement. There were no amputations during the 36-month follow-up period and no haemorrhagic complications in the first 30 days post-treatment. Five patients died (27.8%) during follow-up from unrelated causes. This small study demonstrated that thrombolytic treatment with intravenous rt-PA in selected patients with acute limb ischaemia is feasible.