Immune reconstitution inflammatory syndrome associated with biologic therapy.

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.

Cryptococcosis-IRIS is associated with lower cryptococcus-specific IFN-γ responses before antiretroviral therapy but not higher T-cell responses during therapy.

BACKGROUND: Cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) may be driven by aberrant T-cell responses against cryptococci. We investigated this in human immunodeficiency virus (HIV)-infected patients with treated cryptococcal meningitis (CM) commencing combination antiretroviral therapy (cART). METHODS: Mitogen- and cryptococcal mannoprotein (CMP)-activated (CD25+CD134+) CD4+ T cells and -induced production of interferon-gamma (IFN-γ), IL-10, and CXCL10 were assessed in whole blood cultures in a prospective study of 106 HIV-CM coinfected patients. RESULTS: Patients with paradoxical C-IRIS (n = 27), compared with patients with no neurological deterioration (no ND; n = 63), had lower CMP-induced IFN-γ production in 24-hour cultures pre-cART and 4 weeks post-cART (P = .0437 and .0257, respectively) and lower CMP-activated CD4+ T-cell counts pre-cART (P = .0178). Patients surviving to 24 weeks had higher proportions of mitogen-activated CD4+ T cells and higher CMP-induced CXCL10 and IL-10 production in 24-hour cultures pre-cART than patients not surviving (P = .0053, .0436 and .0319, respectively). C-IRIS was not associated with higher CMP-specific T-cell responses before or during cART. CONCLUSION: Greater preservation of T-cell function and higher CMP-induced IL-10 and CXCL10 production before cART are associated with improved survival while on cART. Lower CMP-induced IFN-γ production pre-cART, but not higher CMP-specific T-cell responses after cART, were risk factors for C-IRIS.