Abstract
A hyperinflammatory ‘cytokine storm’ state termed macrophage activation syndrome (MAS), culminating from a complex interplay of genetics, immunodeficiency, infectious triggers and dominant innate immune effector responses, can develop across disparate entities including systemic juvenile idiopathic arthritis (sJIA) and its counterpart adult-onset Still disease (AOSD), connective tissue diseases, sepsis, infection, cancers and cancer immunotherapy. Classifying MAS using the immunological disease continuum model, with strict boundaries that define the limits of innate and adaptive immunity, at one boundary is MAS with loss of immune function, as occurs in the ‘perforinopathies’ and some cases of sJIA-AOSD. Conversely, at the other boundary, immune hypersensitivity with gain of immune function in MHC class II-associated sJIA-AOSD and with chimeric antigen receptor (CAR) T cell therapy also triggers MAS. This provides a benchmark for evaluating severe inflammation in some patients with COVID-19 pneumonia, which cripples primary type I interferon immunity and usually culminates in a lung-centric ‘second wave’ cytokine-driven alveolitis with associated immunothrombosis; this phenomenon is generally distinct from MAS but can share features with the proposed ‘loss of immune function’ MAS variant. This loss and gain of function MAS model offers immune cartography for a novel mechanistic classification of MAS with therapeutic implications.
【초록키워드】 Cancer immunotherapy, Macrophage, Arthritis, Cytokine storm, COVID-19 pneumonia, therapy, adaptive, Immunity, Pneumonia, Cell therapy, Cancer, variant, Infection, immunodeficiency, Sepsis, genetics, immune, type I interferon, immunothrombosis, T cell, cancers, therapeutic, Connective tissue diseases, immune function, second wave, MHC class II, macrophage activation syndrome, infectious, disease, chimeric antigen receptor, juvenile idiopathic arthritis, innate immune, Trigger, hypersensitivity, triggers, antigen receptor, in some, Implications, immunological disease, complex interplay, innate and adaptive immunity, limits, severe inflammation, Gain, continuum, offer, MHC class, dominant, alveolitis, Hyperinflammatory, responses, immunological, feature, limit, Gain of function, CAR, develop, provide, occur, disparate, patients with COVID-19, Still, 【제목키워드】 COVID-19,