Conditioning Regimens of B Cell Immunodeficiencies Current Perspectives and Future Strategie

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.