Tests for penicillin allergy in man. I. Carrier effect on response to penicilloyl conjugates

Abstract

The value of using benzylpenicilloyl (BPO) conjugates rather than benzylpenicillin (B.Pen.) itself in skin tests and in in vitro diagnostic tests for penicillin allergy in man is assessed. The effect of various carriers on the outcome of these tests has also been investigated in order to find the most appropriate. Skin tests with B.Pen. and BPO conjugates (with polylysine, PL, and human serum albumin, HSA) in penicillin allergic patients were positive in 36 per cent and up to 50 per cent respectively. The two carriers used were equally effective. Negative results were obtained in the non-allergic control subjects. For in vitro studies two tests were selected on the basis of their well established value, the lymphocyte transformation test (LTT) and histamine release from sensitized leucocytes (HRL). In the HRL test BPO conjugates with PL, HSA, bovine serum albumin (BSA) and bovine gamma globulin (BGG) were also compared with B.Pen. The BPO conjugates were all more effective than B.Pen. and the proportion of patients giving positive results with these conjugates was much higher than with B.Pen. (up to 86 per cent compared with 29 per cent). The rank order of effectiveness of the various carriers as judged from maximal histamine release by various penicilloyl conjugates was PL<BSA<HSA<BGG, BGG being the most effective. In the LTT, where BPO:PL, BPO:HSA, BPO:BGG as well as BPO human gamma globulin have been used, the BPO conjugates were also more effective than B.Pen. but the difference was relatively less marked than in HRL test (positive results being obtained with conjugates in up to 92 per cent of patients as compared with 57 per cent with B.Pen.). The rank order of effectiveness of the carriers in the LTT, as judged by comparing the maximum response obtained with each BPO-protein conjugate with the maximum response obtained with BPO:PL, was PL<HSA<HGG<BGG, BGG being the most effective. However, BPO:HGG was effective in lower concentrations. The HRL and LTT were negative in nine out of ten non-allergic subjects, and in control experiments with the carrier molecules alone.