ELISpot responses towards abacavir in HLA-B*5701 positive and negative HIV-infected patients
S. Esser1, F.M. Heinemann2, S. Reuter3, H. Jäger4, A. von Krosigk4, R. Jablonka1, P.A. Horn2, M. Lindemann2
1University of Duisburg Essen, Department of Dermatology, Essen, Germany, 2University Hospital Essen, Institute for Transfusion Medcine, Essen, Germany, 3University of Düsseldorf, Department of Gastroenterology, and Infectiology, Düsseldorf, Germany, 4Practice Dr Jäger, München, Germany
Background: Abacavir (ABC) causes a potentially fatal hypersensitivity reaction (HSR) in 5-8% of HIV-infected patients. HLA-B*5701 testing became available as a predictive test to avoid HSR. But individual cases with ABC-HSR are observed even in HLA-B*5701 negative patients. A safe diagnostic tool to confirm ABC-HSR is mandatory. Therefore, we evaluated an ELISpot method to measure cellular immunity towards ABC.
Methods: ABC-ELISpot was performed in 79 HIV-infected patients (Figure) with clinically determined ABC-HSR (either patch test confirmed or suspected). Patients prior to ABC treatment, either HLA-B*5701 positive or negative, were included as controls. Fourteen patients were female; the average CD4 T cell count was 450/ml (range 15-1143). Peripheral blood mononuclear cells were stimulated by 10 µg/µL of abacavir sulphate in 200 µL of cell culture medium. Following preincubation for 2 days, the cells were incubated in ELISpot plates for 2 further days and the number of interferon-gamma producing cells was measured.
Results: ABC treated patients with HSR (patch test confirmed or suspected) vs. without HSR displayed significantly higher numbers of ABC-specific cells (25.5±14.6 or 4.2±2.0 vs. -0.2±0.4 spots increment, P< 0.01 each). All patients with patch test confirmed ABC-HSR were HLA-B*5701 positive whereas all with suspected HSR were negative. The patients with suspected ABC-HSR displayed reactions similar to those which are HLA-B*5701 positive but have never been treated with ABC.
Conclusion: The data indicate that ABC-ELISpot is a safe diagnostic tool to confirm HSR. The presence of HLA-B*5701 per se (irrespective of ABC treatment) leads to increased ELISpot reactions.
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