Acquired B-cell deficiency secondary to B-cell-depleting therapies

The advantage of the newer biological therapies is that the immunosuppressive effect is targeted, in contrast, to the standard, traditional immunomodulatory agents, which have a more global effect. However, there are un-intended targets and consequences, even to these precise therapeutics, leading to acquired or secondary im-munodeficiencies. Besides depleting specific cellular immune subsets, these biological agents, which include monoclonal antibodies against biologically relevant molecules, often have broader functional immune conse-quences, which become apparent over time. This review focuses on acquired B-cell immunodeficiency, secondary to the use of B-cell depleting therapeutic agents. Among the many adverse consequences of B-cell depletion is the risk of hypogammaglobulinemia, failure of B-cell recovery, impaired B-cell differentiation, and risk of infections. Factors, which modulate the outcomes of B-cell depleting therapies, include the intrinsic nature of the underlying disease, the concomitant use of other immunomodulatory agents, and the clinical status of the patient and other co-existing morbidities. This article seeks to explore the mechanism of action of B-cell depleting agents, the clinical utility and adverse effects of these therapies, and the relevance of systematic and serial laboratory im-mune monitoring in identifying patients at risk for developing immunological complications, and who may benefit from early intervention to mitigate the secondary consequences. Though these biological drugs are gaining widespread use, a harmonized approach to immune evaluation pre-and post-treatment has not yet gained traction across multiple clinical specialties, because of which, the true prevalence of these adverse events cannot be determined in the treated population, and a systematic and evidence-based dosing schedule cannot be developed. The aim of this review is to bring these issues into focus, and initiate a multi-specialty, data-driven approach to immune monitoring.

Automated summary

The advantage of newer biological therapies lies in their targeted immunosuppressive effect compared to traditional immunomodulatory agents. However, unintended consequences can still occur, leading to acquired immunodeficiency. One specific consequence is B-cell immunodeficiency caused by B-cell depleting therapeutic agents, which can result in hypogammaglobulinemia, impaired B-cell differentiation, and increased risk of infections.