Advances and highlights in T and B cell responses to drug antigens

Abstract

The immunological mechanisms involved in drug hypersensitivity reactions (DHRs) are complex, and despite important advances, multiple aspects remain poorly understood. These not fully known aspects are mainly related to the factors that drive towards either a tolerant or a hypersensitivity response and specifically regarding the role of B and T cells. In this review, we focus on recent findings on this knowledge area within the last 2 years. We highlight new evidences of covalent and non‐covalent interactions of drug antigen with proteins, as well as the very first characterization of naturally processed flucloxacillin‐haptenated human leukocyte antigen (HLA) ligands. Moreover, we have analysed new insights into the identification of risk factors associated with the development of DHRs, such as the role of oxidative metabolism of drugs in the activation of the immune system and the discovery of new associations between DHRs and HLA variants. Finally, evidence of IgG‐mediated anaphylaxis in humans and the involvement of specific subpopulations of effector cells associated with different clinical entities are also topics explored in this review. All these recent findings are relevant for the underlying pathology mechanisms and advance the field towards a more precise diagnosis, management and treatment approach for DHRs.

Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions

“…40 In this study, the highest value of sensitivity was found when the proliferation of CD4 + Th2 cells was analysed, without the need for including other subpopulations, since these are the relevant cells to promote the necessary microenvironment for IgE isotype switching in IDHR. 7,35,36,61 Besides, the inclusion of different drug metabolites to increase LTT sensitivity has also been broadly investigated to evaluate NIDHRs to sulphamethoxazole. 51,62,63 In spite of the low LTT sensitivity found in our study with CLV itself, the inclusion of synthetic analogues from both ADs, increased the sensitivity to 65%, with a specificity higher than 90%, similarly to previous studies with different drugs in both, NIDHRs, 46 and IDHRs, 61 although the latest with a different methodology.…”

“… 40 In this study, the highest value of sensitivity was found when the proliferation of CD4 + Th2 cells was analysed, without the need for including other subpopulations, since these are the relevant cells to promote the necessary microenvironment for IgE isotype switching in IDHR. 7 , 35 , 36 , 61 …”

“…30 The hapten-carrier conjugates are recognised by antigen presenting cells (APCs), and, after processing, peptides are presented to B and T cells, triggering their activation. [34][35][36] Based on all of this, our group has recently proposed two potential antigenic determinants (ADs) from CLV, following two different degradation pathways after protein conjugation: AD-I (N -protein, 3-oxopropanamide) and AD-II (N -protein, 3-aminopropanamide).…”

“…A recent study described that the detection of human serum albumin modified sites after culturing with CLV, 20 although other candidate protein carriers such as haptoglobin and immunoglobulin chains have also been proposed 30 . The hapten‐carrier conjugates are recognised by antigen presenting cells (APCs), and, after processing, peptides are presented to B and T cells, triggering their activation 34–36 …”

“… 30 The hapten‐carrier conjugates are recognised by antigen presenting cells (APCs), and, after processing, peptides are presented to B and T cells, triggering their activation. 34 , 35 , 36 …”