SOLUBLE CD4 ANTIGEN REACTIVITY IN INTRAVENOUS IMMUNOGLOBULIN PREPARATIONS - IS IT SPECIFIC

Soluble CD4 antigen (sCD4) was measured in seven commercially availabl e intravenous immunoglobulin preparations (IVIg) by means of a double determinant immunoassay (DDIA), whereby two MoAbs recognizing two dist inct and spatially distant epitopes on CD4 were used to capture and de tect the antigen, respectively. Preincubation of six out of seven IVIg , which were found to be apparently positive for sCD4, with mouse- and bovine-derived serum or purified immunoglobulins completely neutraliz ed DDIA reactivity for sCD4. The inhibition was specific since it was not or only partially observed when IVIg were mixed with whole serum o r purified IgG from rabbit. Extensive absorption of six IVIg on insolu bilized mouse IgG (mIgG) resulted in a complete loss of reactivity. fl uted human anti-mouse antibodies (HAMA) from any of the IVIg displayed a dose-dependent binding in a DDIA, though its extent varied from one preparation to another. Western blot analysis showed that HAMA from a ll IVIg contained no component with a molecular weight identical with or close to that of recombinant CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg (Sandoglobulin and Globuman I.V.) whe n sCD4 was measured with a purchased 'CD4-specific Test Kit', thus sug gesting that HAMA can exceed the absorbing capacity of the sample dilu ent. Taken as a whole, these data indicate that sCD4-based DDIA signal is mostly, if not completely, generated by the presence of human immu noglobulin with anti-mouse immunoglobulin reactivity, thus casting dou bts on the actual occurrence of sCD4 in IVIg.