Table 1.

Classifications of hypersensitivity reactions to biological agents including rituximab.

Type of reaction	Mechanism/Diagnostic criteria	References No≠
Infusion-related reaction	Non-immunologic, monocytes, macrophages, cytotoxic T cells, natural killer cells activation/clinical presentations and course, levels of IL-1, IL-6, and TNF-α	Pichler, 2006; Corominas et al., 2014; Galvão and Castells, 2015; Khan, 2016; Isabwe et al., 2018
Cytokine release reaction	Non-immunologic, monocytes, macrophages, cytotoxic T cells, natural killer cells activation/clinical presentations and course, levels of IL-1, IL-6. and TNF-α	Pichler, 2006; Corominas et al., 2014; Galvão and Castells, 2015; Khan, 2016; Isabwe et al., 2018
Type I reaction (IgE/non-IgE)	IgE or non- IgE dependent mast cell, basophil activation/clinical presentations, level of tryptase, skin tests, BAT	Pichler, 2006; Corominas et al., 2014; Galvão and Castells, 2015; Khan, 2016; Isabwe et al., 2018
Mixed reaction	IgE or non-IgE dependent mast cell, basophil activation and monocytes, macrophages, cytotoxic T cells, natural killer cells activation/clinical presentations, skin tests, BAT, levels of tryptase, IL-1, IL-6, and TNF-α	Pichler, 2006; Corominas et al., 2014; Galvão and Castells, 2015; Khan, 2016; Isabwe et al., 2018
Type III reaction	Not clear, may be related to C-fixing IgM and IgG antibodies and Fc-IgG receptor-mediated neutrophil activation clinical presentations, RF, immunoglobulins, and HACA levels	Karmacharya et al., 2015
Type IV reaction	T-cell mediated or other mechanisms/clinical presentations, immunohistological examination	Henning and Firoz, 2011; Macdonald et al., 2015; Fallon and Heck, 2015; Chen et al., 2018

C, complement; HACA, human anti-chimeric antibody; TNF-α, tumor necrosis factor-α.