Immune Reconstitution Inflammatory Syndrome Associated with Biologic Therapy

Abstract

The use of biologics in the treatment of autoimmune disease, cancer, and other immune conditions has revolutionized medical care in these areas. However, there are drawbacks to the use of these medications including increased susceptibility to opportunistic infections. One unforeseen risk once opportunistic infection has occurred with biologic use is the onset of immune reconstitution inflammatory syndrome (IRIS) upon drug withdrawal. Although originally described in human immunodeficiency virus (HIV) patients receiving highly active antiretroviral therapy, it has become clear that IRIS may occur when recovery of immune function follows opportunistic infection in the setting of previous immune compromise/suppression. In this review, we draw attention to this potential pitfall on the use of biologic drugs.

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

“…Recently, various effective biological agents have been developed for intractable diseases, such as autoimmune diseases and cancer; however, the introduction of these agents has also been found to be associated with IRIS or immunerelated adverse events (Gupta et al 2015). More studies on the prognostic potential of inflammatory markers, including Gal-9, would be helpful to determine whether these markers can predict patients' clinical outcomes.…”

The immunopathogenesis of cryptococcal immune reconstitution inflammatory syndrome

“…A higher proportion of regulatory T cells among subjects who developed CM-IRIS compared to healthy controls at baseline was found in one study [86] while substantial quantitative expansion of these cells with defective immunosuppressive function was found in another study during IRIS [87]. Several studies show no association between decreased proportions of regulatory T cells, including the T effector/T regulatory ratio, and IRIS [86, 88, 89] suggesting that these cells may have a limited role in the pathogenesis of CM-IRIS, however, anti-TNF-α molecules in cryptococcal IRIS enhance Treg and Th2 predominance over Th1 responses [90*]. Further studies focusing on the functional role of regulatory T cells during CM-IRIS are warranted.…”

Immune Reconstitution Inflammatory Syndrome Associated with <i>Pneumocystis jirovecii</i> Pneumonia and Cytomegalovirus Colitis in a Patient with Rheumatoid Arthritis

“…IRIS can also occur in immunocompromised non-HIV patients, such as those who have undergone organ transplantation; those with connective tissue diseases, malignancy, and neutropenia; and women during the postpartum period (2,(6)(7)(8). Potential mechanisms that promote recovery from immunodeficiency include discontinuation or rapid tapering of glucocorticoids or immunosuppressants or both, withdrawal of or reduction in the effects of anti-tumor necrosis factor (TNF)-α antibodies, and the use of immunecheckpoint antagonists (6).…”