N Smith’s research while affiliated with Queen Elizabeth Hospital Birmingham and other places

Forty-two patients with chronic lymphocytic leukaemia (CLL), serum IgG levels < 5.5 milligrams and a history of two or more recent infections, were randomized to receive infusions of 18 g human intravenous immunoglobulin (IVIg) or human albumin placebo every three weeks. During the 12 month study 122 infections were documented but only four were associated with neutropenia. Ten patients (24%) with IgG levels < 3.0 milligrams experienced 65% of the infections. In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections. If three further infections occurred, placebo patients were commenced on 18 g IVIg, and IVIg patients were increased to 24 g IVIg. Approximately 50% of these cases subsequently remained infection free. The study shows the usefulness of prophylactic Sandoglobulin in CLL patients with hypogammaglobulinaemia, and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams.

We investigated the ability of six different pooled human immunoglobulin (PHIG) preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to MPO. All six PHIG preparations inhibited the binding of anti-MPO antibodies from six sera to MPO in a concentration-dependent manner in the concentration range 0.016-10 mg/ml. There was considerable variation in the ability of each PHIG preparation to inhibit the binding of anti-MPO antibody in a given serum. Further differences were seen in the ability of a given PHIG to inhibit anti-MPO binding in different sera. F(ab')2 fragments from two PHIG preparations also inhibited in a concentration-dependent manner anti-MPO binding to MPO in all six sera in the concentration range 0.002-2.65 mg/ml, with a maximum inhibition of 42%. Little inhibition was seen with F(ab')2 of normal human IgG from individual donors (1.8-12.2% at the maximum concentration of 2 mg/ml). F(ab')2 fragments from three anti-MPO containing sera and two affinity-purified anti-MPO antibodies were eluted by affinity chromatography from Sepharose-bound PHIG F(ab')2 and showed anti-MPO antibody activity. We have shown that PHIG and F(ab')2 fragments of PHIG inhibit anti-MPO binding to MPO, and further that F(ab')2 fragments of PHIG bind to F(ab')2 fragments of anti-MPO antibodies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti-MPO antibodies, and are consistent with an anti-idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti-MPO-positive sera implies differences in their anti-idiotype content, while the variability of the inhibitory effect of a particular PHIG preparation between different sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an important determinant of their therapeutic effect.

This study demonstrates that pooled human immunoglobulin (PHIG) contains anti-idiotypes to anti-myeloperoxidase (MPO) antibodies and can inhibit the binding of anti-MPO to MPO. The variability seen in the inhibitory effect of different PHIG preparations in the same and also in different patient sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies.

Summary Anti-Rho(D) immunoglobulin (anti-D) contained more high molecular weight (HMW) IgG polymers than intravenous non-specific immunoglobulin (i.v. Ig). The low-dose anti-D and high-dose i.v. Ig regimens used to treat idiopathic thrombocytopenic purpura (ITP) therefore contained similar total amounts of HMW IgG. In vitro, the HMW IgG polymers were more effective competitive inhibitors of monocyte phagocyte Fc receptors than monomeric IgG. The IgG subclass composition of anti-D and i.v. Ig were both similar to normal human plasma. We conclude that the HMW IgG content but not the IgG subclass composition of anti-D may explain its low-dose therapeutic efficacy in ITP.

Previous work in our department showed that after blood transfusion, the platelet count often falls to levels which are clinically significant. The probable site of platelet sequestration was identified as the spleen, and post-transfusion thrombocytopenia was prevented by blood filters which remove microaggregate debris from the donor blood. Since the duration of the thrombocytopenia has not been investigated, the purpose of the present study was to establish the rate of onset and duration of post-transfusion thrombocytopenia following packed red blood cell transfusions. In addition, the effect of spleen size, patients' diagnosis and post-transfusion history were examined. These observations provide interesting new data on the mechanisms involved in this phenomenon.