Probable Causes and Mechanisms of Imm ediate Type Hypersensitivity Objectionable Adverse Reactions towards Genetically Modified Tuberculosis Allergens in Children

Abstract

The study describes probable causes and mechanisms of development of local and systemic immediate type reactions in children after skin test with recombinant tuberculosis allergen (ATP, Diaskintest) as well as similar Danish recombinant allergen C-Tb. Both of these preparations consist of M. tuberculosis ESAT6 and CFP10 fusion proteins produced by bacteria-producents other than M. tuberculosis, Diaskintest (DST) has been untroduced into clinical practice in Russia as a tool for preventive screening for tuberculosis since 2009 and since 2015 it has replaced the original Mantoux text with tuberculin in children and adolescents from 8 to 17. The most common side effects not anticipated by the instruction developed within 1 to 12 h after injection and were represented by local or non-life threatening systemic symptoms: fever up to 39 °C lasting up to 24 h, painful excessive edema with erythema on the forearm, and, sometimes herpetiform blisters on the skin. In 72 h, the papula at the injection site was moderate, but the hyperemia around it was considerable. The most likely reason for this type of response could be the development of Type III hypersensitivity (associated with immune complexes), and/or antibody-independent anaphylactoid response to the ESAT6/CFP10 protein or contaminating bacterial culture components. To prevent possible side effects, we recommend to observe the patients for at least 15 min after the injection of RTA, and to be ready to respond in case of anaphylactic development.