Conditioning Regimens of B Cell Immunodeficiencies Current Perspectives and Future Strategie View PDF

Soumitha Mondal
Medicine, Dr. BR. Ambedkar Medical College And Hospital, India

Published on: 2024-08-02

Abstract

As primary immunodeficiencies (PI) have evolved rapidly over the past 20 years, and immune dysregulation has been recognized as a characteristic in some, the term “inborn errors of immunity” (IEI) has become a more comprehensive description of these conditions. Monogenic disorders of the immune system have historically been characterized as disorders affecting T cells, B cells, or a combination of T and B cells. Innate immune disorders can also be classified as a monogenic disorder. Recently, immunologists have also recognized that some genes are incompletely penetrant or express themselves differently across genotypes and result in IEI due to incomplete penetrance or variable expression. In the IUIS classification of immune deficiencies, small molecule inhibitors and biologics are used to treat a subset of disorders called immune dysregulation. Until recently, the only treatment options were prompt treatment of infections, gamma globulin replacement, and bone marrow transplant. Small molecule inhibitors, biologics, gene therapy, and adoptive transfer of virus-specific T cells are all available to fight viral infections in immunocompromised patients. Over the past two decades, several significant contributions have fuelled rapid advancements in clinical immunology. As a result of educational efforts to recruit young immunologists into the field, a world-wide community of clinicians and researchers interested in rare diseases has grown. In addition, IEI’s efforts to raise global awareness have contributed to international collaborations, as have advances in diagnostic genetic testing, newborn screening, molecular biology, gene correction, immune modulators, and the ex vivo expansion of engineered T cells. The purpose of this short communication is to provide a brief compendium of IEI that affect B cells at specific stages of their development, as well as some educated viewpoints on how these disorders may be managed in the future.

Keywords

B cells, Immunodeficiency, Humoral immunity

Introduction

Both extracellular and intracellular pathogens are protected by the anamnestic immune response. In order to eliminate invading pathogens and generate sterilizing immunity, two distinct subsets of cells, the B cells (which target extracellular pathogens) and the T cells (which eliminate intracellular pathogens), play complementary roles. B cell receptors (BCRs) and immunoglobulins (Igs) play a significant role in B cell-associated immune responses. The understanding of how the Ig molecule interacts with its cognate antigen and triggers the B cell response has led to revolutions in two major domains of modern healthcare: laboratory diagnostics and immunotherapy. Without Kohler and Milstein discovering the process to generate monoclonal antibodies (MAb) in the early to mid-1970s, laboratory medicine would have been in a state of arrested development. A number of diseasespecific biologics have also been developed since this seminal discovery in the subsequent decades. A number of key molecular regulators of B cell development and responses have been identified from studying inborn errors of B cell immunity [1]. Humans were first diagnosed with X-linked Agammaglobulinemia (XLA) as an inborn error of immunity (IEI). Based on an analysis of clinical presentations and laboratory findings in patients with predominantly B cell IEI, this review highlights how our understanding of B cell development and humoral immunity has evolved over the past 70 years [2]. The report begins with a brief history of XLA, one of the prototypical B cells IEIs, followed by an overview of what we currently know about a few representative B cell IEIs that are routinely considered as part of the differential diagnosis in patients with deficiencies in B cells and antibodies. Following our discussion of diagnosis and treatment options for B cell IEI, we finish by offering some thoughts on how the future may affect the way we diagnose and treat B cell IEI [3].