Improved Compatibility of ALG Therapy by Application of Aggregate Free Globulin

Abstract

Horse anti-human lymphocyte globulin (ALG) solutions contain, like human γ-globulin preparations, a varying amount of IgG aggregates, which increase during longer periods of storage. Aggregate formation does not impair the immunosuppressive potency of ALG, as has been shown by prolongation of skin allograft survival time in primates. Deaggregated ALG, which can be obtained by ultracentrifugation at 100,000 g over 2 h, is less immunogenic than aggregate containing ALG. The clinical compatibility of ALG was significantly improved by ultracentrifugal deaggregation.

Anaphylactoid reactions to infusions of plasma protein and human serum albumin Role of aggregated proteins and of stabilizers added during production

“…PP or HSA solutions contain a considerable amount of aggregated proteins, the nature of which is not yet completely clear. It is known, however, that IgG aggregates can be responsible for incombatibility reactions after infusion of human gammaglobulin or anti-lymphocyte globulin (Barandun et al, 1962;Ring et al, 1976b) in man as well as in experimental animals (Ring et al, 1978b). Although commercial HSA solutions usually contain at least 95% human serum albumin-most of them contain in fact 99%-the remaining 1 to 5% 'contamination' with globulins or other serum proteins cannot be ruled out as the pathogenic factor.…”

Elimination and organ distribution of intravenously administered allogeneic and xenogeneic IgG modifications (Standard IgG, F(ab′)2-fragments andβ-propiolactone treated IgG) in dogs

“…Often this anticomplementary activity is connected to the aggregate fraction of the globulin solution [23--26]. By deaggregation the compatibility of gammaglobulin solutions has been improved in animal experiments [25] as well as in clinical studies [26], when deaggregated xenogeneic IgG of known in-vitro anticomplementary activity was infused. The fact that our dogs tolerated the intravenous injection of allogeneic and xenogeneic standard gammaglobulin does, however, not allow conclusions for the clinical route of application of this preparation.…”

Immunosuppression with Antilymphocyte Globulin (ALG) in the Treatment of Ophthalmic Disorders

“…5, 7 and 13) were given so-called 'one-shot' tolerance pretreatment with 30 mg/kg horse IgG admin istered 24 h before the first ALG infusion. Prior to clinical application the ALG was deaggregated daily in the ultracentrifuge (Beckman Instruments) at 100,000 g for 2 h under sterile conditions [42], The daily dose of 20 mg/kg (for some exceptions, see table I) was diluted in 500 ml saline and infused intravenously (5 ml/min). During the period of ALG treatment, the patients' clinical symptoms of incompatibility (hypotension, tachycardia, skin symptoms, etc.)…”