Lack of immune response to mouse IgG in previously untreated haemophilia A and haemophilia B patients treated with monoclonal antibody purified factor VIII and factor IX preparations.

Immunoaffinity purification of factor VIII and factor IX results in the inclusion of trace quantities (50 ng 100 IU(-1) ) of mouse protein in the final product. It is possible that infusion of extremely low levels of proteins might induce human antimouse antibody (HAMA) responses. To test this possibility, IgG, IgM and IgE antibodies to mouse IgG were assessed in previously untreated haemophilia A and haemophilia B patients (n = 9 and n = 11, respectively) who received monoclonal antibody (MAb) purified factor VIII (Monoclate-P® Antihaemophilic Factor [Human] Centeon, King of Prussia, PA) or factor IX (Mononine® Coagulation Factor IX [Human] Centeon). HAMA were evaluated prior to and 2-42 months after initial treatment. IgE antibodies to mouse IgG were undetectable (< 19 ng ML(-1) ) at all time points. Antimouse IgG levels for Monoclate-P-treated patients averaged (mean±SD) 0.40±0.18 µg mL(-1) prior to treatment, and 0.64±0.43 µg mL(-1) at the time of last observation (P > 0.05, not significant [n.s.]). Respective values for antimouse IgM in these patients were 2.48±1.20 µg mL(-1) and 2.85±1.63 µg mL(-1) (P > 0.05, n.s.). Antimouse IgG levels for Mononine-treated patients averaged 0.48±0.52 µg mL(-1) prior to treatment, and 0.66±0.59 µg mL(-1) after 3 months of therapy (P > 0.05, n.s.). Respective values for antimouse IgM in these pa-tients were 1.94±1.52 µg mL(-1) and 1.77±0.99 µg mL(-1) (P > 0.05, n.s.). Lack of immunogenicity of traces of mouse protein in these preparations is supported in that none of the patients assessed developed anaphylactoid reactions during treatment.

Pancreatic pseudocyst resolution after parathyroidectomy for hyperparathyroidism.

Hyperparathyroidism is a rare cause of pancreatic inflammatory disease. Appropriate treatment of coexistent hyperparathyroidism and pancreatitis, especially when complicated by pseudocyst formation, is unsettled. We describe two patients with primary hyperparathyroidism who developed pancreatitis associated with multiple pseudocysts. The largest cyst in each patient was 9 and 5 cm, respectively. After correction of hyperparathyroidism and normalization of serum calcium levels by removal of a parathyroid adenoma, the pseudocysts resolved in both patients, as documented with computed tomography. We conclude that uncomplicated pancreatic pseudocysts in patients with primary hyperparathyroidism can be treated expectantly. Surgical correction of hyperparathyroidism and normalization of serum calcium levels should precede pancreatic intervention when possible, since pseudocyst resolution is likely and the risks of postoperative hypercalcemia are avoided.

Lack of immune response to mouse IgG in hemophilia A patients treated chronically with Monoclate, a monoclonal antibody affinity purified factor VIII preparation.

Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (less than 50 ng/100 I. U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgM and IgE anti-mouse IgG antibody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate infusion. Data is presented demonstrating that induction of HAMA upon Monoclate treatment does not occur. The low level of mouse IgG contained in Monoclate appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate in these clinical studies.