Rheumatologist & epidemiologist at Brigham and Women's Hospital, Section of Clinical Sciences, and Professor of Medicine at Harvard Medical School.
- Tweets4.4K
- Following651
- Followers2.2K
- Likes2.9K
ALT The vicious cycle of macrophage activation syndrome. Antigen-presenting cells (macrophages and dendritic cells) and lymphocytes (primarily CD8+ T cells) form a cytokine-generating vicious cycle driven by multiple activation pathways (red arrows). Under normal conditions, this positive feedback loop is stopped by inhibitory pathways (blue), including killing of activated antigen-presenting cells and lymphocytes, regulatory T cells, and elimination of triggers such as viruses (not shown). In MAS, factors leading to uncontrolled activation of this vicious cycle (gray boxes) include genetic and acquired defects in cell-cell killing, excess stimulation (Still’s disease activity, infection, malignancy), and “IL-2 theft” by highly activated CD8+ T cells expressing the high-affinity IL-2 receptor α chain CD25.
ALT Blocking the vicious cycle in MAS. Corticosteroids are broadly immunosuppressive and form the foundation of treatment. Anakinra, JAK inhibitors, and tocilizumab block cytokines derived from antigen-presenting cells that stimulate T cells, including IL-1β, type I interferons, and IL-6; JAK inhibitors also block IL-2, IL-12, and IL-15. Calcineurin inhibitors (tacrolimus and cyclosporine) reduce T cell activation and thereby production of IFN and IL-2, while etoposide depletes cycling lymphocytes, especially activated CD8+ T cells. Emapalumab blocks IFN, as do JAK inhibitors. Treatment of Still’s disease activity, infection, or malignancy reduces overall immunostimulation. Rituximab reduces antigen load in EBV-associated MAS. IVIG may control infectious triggers while blocking other immunostimulants or dampening inflammation via inhibitory Fc receptors, though is generally considered a weak agent against MAS.
ALT FoxO1 Deficiency in M-MDSCs Exacerbates B Cell Dysfunction in Systemic Lupus Erythematosus. Graphical abstract created with BioRender
ALT Arthritis & Rheumatology Immunology for the Rheumatologist review series banner
ALT Figure 1. Initiation of DMARDs by drug class or category in children with JIA, 2001-2022. This figure displays the percentage of total new episodes per year of each DMARD class or category in children with JIA in MarketScan between the years 2001 and 2022. A DMARD claim was considered a new episode if a patient had no claim for the same DMARD within 365 days prior to the current DMARD claim.
ALT Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project. Graphical abstract created with BioRender
