Table 1.

Blood biomarkers in human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) who developed cryptococcal meningitis immune reconstitution inflammatory syndrome (CM-IRIS).

Phase	Biological Activity	Biomarkers	Reference
Prior to ART initiation	Granulocyte activation, systemic oxidative stress	↑ oxidases, arginases, integrins, matrix metalloproteinases (MMP), etc.	Musubire et al., 2018 [78] Vlasova-St. Louis et al., 2018 [31]
Prior to ART initiation	Transcriptomic profiles of peripheral mononuclear cells	↓ type I interferons (IFN I), antiviral defense gene expression	Vlasova-St. Louis et al., 2018 [31]
	In vitro stimulated mononuclear cells	↓ interferon-gamma (IFN-γ)	Chang et al., 2013 [77]
	Activated monocyte status Activated CD14+CD16++ monocyte	↑ IL-6, C-reactive protein, serum amyloid A and D-dimer, sCD14, ↑ TNF-α and IL-6	Sandler et al., 2011 [79] Meya et al., 2017 [80]
	Increased levels of blood cytokines and chemokines	IL-6, IL-18, TNF-α, IL-5, IL-7, IL-17, GM-CSF, CCL11, and CXCL10	Meya et al., 2019 [84] Rateni et al., 2018 [85] Akilimali et al., 2017 [86]
	Poor B cell function upon stimulation with	↓ IgM antibodies secretion in response to Cryptococcal antigens	Yoon et al., 2019 [28]
At the time of CM-IRIS events	Transcriptomic profiles of peripheral mononuclear cells	Early CM-IRIS: ↑ inflammasome components: IL1B, Casp1, AIM2 NAIP, NLRP3, etc. Late CM-IRIS: ↑ IFNG, IL27, KLRB1, CD3, CD247, CD8, IL2RB	Vlasova-St. Louis et al., 2018 [31]

Abbreviations: ↑ increase; ↓ decrease; CM-IRIS—cryptococcal meningitis IRIS; ART—antiretroviral therapy; IFN—interferon; IL—interleukin; TNF—tumor necrosis factor; GM-CSF—granulocyte-macrophage colony-stimulating factor; CNS—central nervous system; sCD14—soluble CD14.