Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide

Abstract

Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens.

Keywords: auto-immune; children; immunomodulatory drugs; immunosuppressed; vaccination.

Figure 1

Kinetics of the antibody response in a primary and secondary immune response. Following a first exposure with an antigen, there is an interval of 10-14 days before the production of IgG antibodies, which occurs after the interaction of naive B and T cells, which become effector cells and develop into gentianée-specific memory B cells, short-lived plasma cells and long-lived plsame cells. Then, long-lived plasma cells in migrate in the bone marrow and continue to secrete IgG antibodies. However, with the time the antibodies decrease often under the protective levels. During a secondary exposure with the vaccine or the antigen, memory B and T cells are rapidly reactivated, with a more rapid and higher IgG increase that usually last longer. However, in immunosuppressed children, the peak of the antibody response is expected to be lower, and the antibodies are expected to decrease more rapidly after vaccination.

Figure 2

Steps of the activation and proliferation of T cells and B cells during an immune response, and possible targets of the immunosuppresive drugs. During an immune response, naïve T cells recognize a peptide antigen presented on the surface of antigen-presenting cells (APCs) in the MHC molecule via the binding of their T-cell receptor (TCR) and co-stimulatory signals given by the CD80 and CD86 on the surface of DCs and CD28 on T cells. This activates various signal transduction pathways in T cells, which activate the transcription of various factors that induce the expression of several molecules, such as IL-2. Naïve B cells that have bound antigen to their surface Ig receptors require co-stimulatory signals from T cells that are specific for the same antigen. This allows initiating a germinal center reaction with proliferation and mutation of the antibody genes and then differentiate into antibody-producing plasma cells and memory B cells. Each of the steps of the immune response can be the target of an immunosuppressive drug: 1) the depletion of the specific or cognate T and/or B cells (e.g. anti-CD20); 2) interference with the co-stimulatory signals (e.g. CTLA4-analog); 3) blockade of the intracellular signal (e.g. calcineurin inhibitor or mTOR inhibitor); 4) inhibition of DNA synthesis and cell proliferation (e.g. purine analog, or alkylating agents); 5) modulation of the effector T or B cell responses (various anticytokine monoclonal antibodies), included blocking inflammation reducing antigen presentation (anti-IL6, TNF, JAK, etc.).