T Cell Abnormalities in X-Linked Agammaglobulinaemia: an Updated Review

Abstract

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency (PID) resulting from a defect in the B cell development. It has conventionally been thought that T cells play a major role in the development and function of the B cell compartment. However, it has also been shown that B cells and T cells undergo bidirectional interactions and B cells also influence the structure and function of the T cell compartment. Patients with XLA offer a unique opportunity to understand the effect of absent B cells on the T cell compartment. In this review, we provide an update on abnormalities in the T cell compartment in patients with XLA. Studies have shown impaired memory T cells, follicular helper T cells, T regulatory cells and T helper 17 in patients with XLA. In addition, these patients have also been reported to have abnormal delayed cell-mediated immune responses and vaccine-specific T cell-mediated immune responses; defective T helper cell polarization and impaired T cell receptor diversity. At present, the clinical significance of these T cell abnormalities has not been studied in detail. However, these abnormalities may result in an increased risk of viral infections, autoimmunity, autoinflammation and possibly chronic lung disease. Abnormal response to SARS-Cov2 vaccine in patients with XLA and prolonged persistence of SARS-Cov2 virus in the respiratory tract of these patients may be related to abnormalities in the T cell compartment. Keywords X-linked agammaglobulinaemia (XLA) • Primary Immunodeficiency (PID) • Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) • Bruton tyrosine kinase (BTK) • T cell receptor (TCR) • T follicular helper cells (TFH)Abbreviations XLA X-linked agammaglobulinaemia PID Primary immunodeficiency BTK Bruton tyrosine kinase BCR B cell receptor GC Germinal centre APC Antigen-presenting cells TCR T cell receptor MHC Major histocompatibility complex FDCs Follicular dendritic cells CVID Common variable Immunodeficiency ELISPOT Enzyme-linked immunospot CTL Cytotoxic T lymphocytes Tfh T follicular helper cells Tregs Regulatory T cells Th17 T helper 17 cells RTE Recent thymic emigrants DCs Dendritic cells CDR3 Complementarity determining region 3 GvHD Graft versus host disease EBV Epstein-Barr virus CMV Cytomegalovirus

From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature

“…Furthermore, early reduced levels of CD19 and CD20 compared to T cells, along with decreased levels of immunoglobulins, underscore a significant deficiency in B cells, which can be assigned to the presence of the BTK mutation. Moreover, the progressive unbalanced distribution of cellular immunity observed in the patient, potentially influenced by the effects of both mutations, as recent study indicated the impaired cellular immunity in BTK deficiency, including abnormal memory T cells, T regulatory cells, delayed cell-mediated immune responses, defective T helper cell polarization and impaired T cell receptor diversity [ 9 ].…”

Regulation of CD8 T cell by B-cells: A narrative review

“…Few data are available regarding CD8 T cells in XLA, which may shed light on our understanding of the role of B cells in the different types of CD8 T cell responses. It should be noted that BTK is also expressed in other immune cells ( 48 ).…”

Severe Tick-Borne Encephalitis (TBE) in a Patient with X-Linked Agammaglobulinemia; Treatment with TBE Virus IgG Positive Plasma, Clinical Outcome and T Cell Responses

“…Patients have very low levels (< 1%) of mature B lymphocytes and are therefore totally unable to produce immunoglobulins. The disease is also called Bruton´s disease and affects 1 in 200.000 male births [ 3 , 4 ]. Patients with XLA suffer from recurrent bacterial infections from an early age, and are at an increased risk of encephalitis due to enterovirus infection.…”