No abstract

T cells are indisputably critical mediators of atherosclerotic cardiovascular disease (CVD), where they secrete pro-inflammatory cytokines that promote vascular pathology. Equally well-established is the fact that autoimmune diseases, which are mediated by autoreactive T cells, substantially increase the risk of developing CVD. Indeed, as immunomodulatory treatments have become more effective at treating end-organ pathology, CVD has become a leading cause of death in patients with autoimmune diseases. Despite this, investigators have only recently begun to probe the mechanisms by which autoreactive T cells promote CVD in the context of autoimmune diseases. T cells are best-studied in the pathogenesis of systemic vasculitides, where they react to selfantigen in the vessel wall. However, newer studies indicate that T cells also contribute to the increased CVD risk associated with lupus and rheumatoid arthritis. Given the central role of T-cell-derived cytokines in the pathogenesis of psoriasis, the role of these factors in psoriatic CVD is also under investigation. In the future, T cells are likely to represent major targets for the prevention and treatment of CVD in patients with autoimmune diseases.

BackgroundMonogenic autoinflammatory diseases (AID) are caused by mutations in innate immune genes. The effects of these mutations on allergic inflammation are unknown.ObjectivesWe investigated allergic, immunological and clinical phenotypes in FMF (familial Mediterranean fever), CAPS (cryopyrin-associated periodic syndrome), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), HIDS (hyper-IgD syndrome), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), CANDLE (chronic atypical neutrophilic dermatosis, lipodystrophy, elevated temperature) and SAVI (STING-associated vasculopathy of infancy).MethodsIn this cross-sectional study, clinical data were assessed in 425 patients with AID using questionnaires and chart reviews. Comparator data were obtained from public databases. Peripheral blood mononuclear cells obtained from 55 patients were stimulated and CD4+ cytokine production assessed.ResultsClinical laboratory features of Type 2 immunity were elevated in CAPS but reduced in most AID, particularly DADA2. Physician-diagnosed allergic diseases were prevalent in multiple AID, including CAPS and DADA2. T helper 2 (Th2) cells were expanded in CAPS, TRAPS and HIDS; Th9 cells were expanded in HA20.ConclusionsCAPS is characterised by an enhanced Type 2 signature, whereas FMF and CANDLE are associated with reduced Type 2 responses. DADA2 is associated with reduced Type 2 responses but a high rate of physician-diagnosed allergy. Therefore, NLRP3-driven autoinflammation may promote Type 2 immunity, whereas AID like DADA2 may manifest clinical phenotypes that masquerade as allergic disorders. Further investigations are needed to determine the contribution of autoinflammation to allergic clinical and immunological phenotypes, to improve the treatment of patients with AID.