The uses of intravenous immune globulin in collagen vascular disorders

Abstract

Studies in our laboratory demonstrated that the long-term administration of intravenous immune serum globulin in patients with common variable hypogammaglobulinemia produced increased suppressor activity, which resulted in diminished in vitro B cell immunoglobulin synthesis. These studies suggested that intravenous immune globulin therapy might be a useful modality in altering immunoregulation in patients with collagen vascular autoimmune disease. In the present preliminary study, two groups of patients with collagen vascular disease were chosen: systemic lupus erythematosus and primary Sjögren's syndrome. Patients with systemic lupus erythematosus with mild clinical disease were chosen to minimize the risk of adverse effects on the disease process, particularly specific organ involvement (e.g., lupus nephritis). Each patient was used as his or her own clinical and laboratory control. Patients received 300 mg/kg of intravenous immune globulin every 4 weeks. As a whole the patient group did not experience any adverse effects from the intravenous immune globulin therapy. No clinical or laboratory changes were observed in one patient with systemic lupus erythematosus and one patient with Sjögren's syndrome. In the other patient with Sjögren's syndrome, there were subjective changes of improved well-being and increased energy levels without any objective changes in the sicca syndrome. There was a slight steroid-sparing effect (10 to 3 mg/day) but no effects on the sedimentation rate, the antinuclear antibody, or rheumatoid factor serologic studies. In a patient with steroid-dependent systemic lupus erythematosus, there was marked clinical improvement of the cutaneous vasculitis after the third infusion, with reduction in her oral steroid requirements from 25 to 7.5 mg/day. The fifth patient, with a lupus anticoagulant and multiple miscarriages, was treated with an induction regimen of 0.4 gm/kg of intravenous immune globulin for 4 days after she became pregnant. Shortly thereafter for the first time, the lupus anticoagulant became negative with a decrease in anticardiolipin serologies. However, despite maintenance infusions given every 3 weeks at 500 mg/kg, the anticardiolipin antibody titers increased, and her lupus anticoagulant levels returned to previous ranges. This patient was treated concomitantly with low-dose anticoagulants (aspirin) and low-dose heparin. She delivered a normal, healthy child at 36 weeks' gestation. The placenta was grossly and microscopically normal, with no evidence of thrombosis. These preliminary studies indicate that select patients with collagen vascular disorders may benefit, although in some cases transiently, from intravenous immune globulin therapy. Further studies are needed to identify better those patients with collagen vascular disorders that might respond to intravenous immune globulin as adjunct therapy and select an optimal dosage regimen.