Hapten-Specific Lymphocytes: Biomarkers of Allergy in Man
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Drug Information Journal. Vol. 31, pp. 1379-1382, 1997 Printed in the USA. All rights reserved.
HUMAN HAPTEN-SPECIFIC LYMPHOCYTES: BIOMARKERS OF ALLERGY IN MAN VERAD. M. STEJSKAL, PHD Department of Clinical Chemistry, Danderyds Hospital and Karolinska Institute, Stockholm, Sweden
Environmental pollutants and other chemicals may have increasing impact on the immune system of human beings. Disregulation of the immune system by chemicals may be one of the reasons why the frequency of allergies and autoimmune diseases increases. Human hapten-specific memory lymphocytes can be detected in the blood of patients with druginduced immunologic side effects but not in similarly exposed healthy individuals. The immune reactivity of human lymphocytes in vitro to white coloring agent-titanium dioxide (TiO,), and mercurial conservatives thimerosal and phenylmercury-has been studied. It was found that out of 650 patients tested, 3% reacted to titanium dioxide. The percentages for phenylmercury and thimerosal were 14% and 7%. respectively. Human memory cells can be used as markers of susceptibility in future choices of appropriate additives in pharmaceutic products. Key Words: Haptens; Memory lymphocytes; MELISA; Titanium; Thimerosal; Drug
allergy
INTRODUCTION THE INDUSTRIAL REVOLUTION and the demand for a high standard of living contribute greatly to the increasing impact of environmental pollutants and other chemicals on the immune system of human beings (1). Disregulation of the immune system by chemicals may be one of the reasons why the prevalence of allergies and autoimmune diseases is increasing. As regards pharmaceuticals, which are often used on a long-term basis, it is of great importance that these products are devoid
Presented at the DIA Workshop “Immunotoxicity of Pharmaceuticals: Current Knowledge, Testing Strategies, Risk Evaluation & Consequences for Human Health,” October 2 4 1996, Montreux, Switzerland. Reprint address: Dr.Vera Stejskal, Deparunent of Clinical Chemistry, Danderyds Hospital, S-182 88 Danderyd, Sweden.
of any potentially harmful additives which could induce unwanted side effects. Such side effects may be falsely blamed on the pharmaceutically active drug. Modem immunology provides the tools for measurement of biological events which may occur in the body upon exposure to low molecular substances. Such biomarkers may be divided into three different categories: markers of exposure, markers of susceptibility, and markers of health effects (1,2).
BACKGROUND AND DISCUSSION Human memory lymphocytes can be restimulated with various immunogenic substances such as proteins, viruses, or bacterial antigens in vitro. This so-called lymphocyte proliferation test (LTT, LST) has been used for years for the testing of cell-mediated immunity by clinical immunologists. In the immunotoxicologic laboratory, the test can be used
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Vera D.M. Stejskal
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for the detection of bacterial impurities in pharmaceutical preparations obtai
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