Clinical Spectrum and Therapeutic Options in Monogenic CTLA-4-, LRBA-, or SOCS1-Related Primary Immune Regulatory Disorders.

Abstract

Primary immune regulatory disorders (PIRDs) are defined by a loss of immune homeostasis and are clinically characterized by autoimmunity, autoinflammation, lymphoproliferation, infection susceptibility, and cancer predisposition. An increasing number of genetic defects have been described that result in impaired regulation of immune responses. Evolving clinical manifestations and variable disease spectrum lead to significant diagnostic challenges and treatment conundrum. In this review, we present 3 clinical vignettes of PIRDs, including cytotoxic T-lymphocyte-associated protein 4 haploinsufficiency, lipopolysaccharide-responsive beige-like anchor protein deficiency, and suppressor of cytokine signaling 1 deficiency, to illustrate step-by-step approaches to diagnostic evaluation, disease assessment, and therapeutic management. We describe tailored treatment strategies, including immunomodulatory agents and hematopoietic stem cell transplantation, that address each patient's clinical manifestations, treatment response, and adverse effects. We also explain the clinical decision-making process, incorporating immunologic insights from the specific underlying genetic defects, relevant literature, and pearls from our clinical experience. Through these cases, we aim to offer a practical framework for clinicians managing patients with PIRDs.