In vitro lymphocyte proliferation in the diagnosis of allergy to phenoxymethylpenicillin

Background The aim of this study was to investigate in vitro lymphocyte proliferation in the diagnosis of allergy to phenoxymethylpenicillin (PcV), comparing chemically reactive PcV, added to cell cultures in unconjugated form, to a PcV-PLL (poly-L-lysine) conjugate as antigens. Side-chain specificity of lymphoproliferative responses was investigated with reactive benzylpenicillin (PcG) and bacampicillin. Methods Seventeen patients with a history of hypersensitivity reactions in connection with PcV treatment were studied by means of the lymphocyte transformation test (LTT), the radioallergosorbent test (RAST), skin tests (prick and intracutaneous), and oral challenge with PcV. LTT was also performed in 20 control subjects exposed to PcV therapeutically, and in eight subjects with occupational exposure to this penicillin. Results Nine patients had a positive in vivo test to PcV (five by oral challenge, three by intracutaneous test, and one by both tests), and six were challenge-negative. When reactive PcV was used as antigen in LTT, positive LTT responses were observed in five of the nine patients with a positive in vivo test, and two of them were also side-chain specific. Positive LTT responses with reactive PcV also correlated with a positive RAST in five of seven subjects. None of the six patients with a negative challenge test, and only one of the 28 controls showed a positive LTT result with reactive PcV. Thus, the specificity of LTT with reactive PcV was 96%. In contrast, when PLL-conjugated PcV served as antigen, four challenge-negative subjects and 11 controls were LTT-positive. Conclusions The results of this study indicate that LTT with chemically reactive PcV could be useful as an in vitro complement in the diagnosis of PcV allergy and as a tool to reveal the side-chain specificity of peripheral blood lymphocytes. A positive LTT to PLL-conjugated PcV may be an indicator of immunization, but not necessarily allergy, to the penicilloyl structure.