Search Results (2)

Raynaud’s Phenomenon (RP) serves as the clinical sentinel for systemic autoimmunity, frequently predating connective tissue disease diagnosis by years. While RP is a largely benign functional vasospasm in the general population, its prevalence in Systemic Sclerosis (SSc) approaches 99%. A fundamental mystery in Rheumatology is the divergent fate of the microvasculature across connective tissue diseases. RP can occur in other autoimmune diseases; it is usually not associated with the relentless transition to obliterative vasculopathy. In SSc, the vessel lumen is physically occluded by intimal proliferation and perivascular fibrosis, yet the mechanism triggering this ischemia remains poorly understood. Beyond the classic tri-phasic color change, SSc patients frequently report other early distressing sensory symptoms, specifically intense pruritus, neuropathic burning, and profound edema. Historically dismissed as secondary to ischemia, we propose that these sensations are primary markers of the underlying pathological driver. We challenge the traditional B-cell/T-cell-centric view of SSc by introducing the concept of autoallergy. We hypothesize that these sensory symptoms represent chronic, IgE-mediated activation of resident mast cells. This mast cell-driven circuit, triggered by SSc-specific autoantigens, acts as a persistent secretory pump for pro-fibrotic cytokines, fundamentally distinguishing SSc vasculopathy from the purely inflammatory vascular patterns seen in other connective tissue diseases. Targeting the IgE–mast cell axis early in the course of the disease may offer a novel therapeutic window to halt the transition from functional vasospasm to permanent structural obliteration. Full article

Background: Chronic spontaneous urticaria (CSU) is defined as the recurrence of unprovoked transient wheals and itch for more than 6 weeks. Currently, there is an unmet need concerning response prediction in CSU. The present study investigated biomarkers of type I and type IIb autoimmunity as potential predictors of response to omalizumab in CSU. Materials and methods: Differences in levels of IgG and IgE autoantibodies targeting the high- and low-affinity IgE receptors (FcεRI and FcεRII, respectively), as well as spontaneous and specifically triggered leukotriene C (LTC)4 release by basophils from the investigated subjects, were evaluated in 18 consecutive, prospectively enrolled CSU patients and 18 age- and sex-matched, healthy non-atopic controls. Results: The patients with CSU had higher levels of anti-FcεRI IgE (542 (386.25–776.5) vs. 375 (355–418), optical density (OD), p = 0.008), and IgG (297 (214.5–431.25) vs. 193.5 (118–275) OD, p = 0.004) autoantibodies relative to the controls. Simultaneous anti-FcεRI IgG and IgE positivity (i.e., both autoantibody levels above the respective cut-offs) was recorded only in late- and non-responders (3/8 and 1/2, respectively). Discussion: Significantly higher anti-FcεRI IgE autoantibody levels were found in the CSU patients as compared to the controls, supporting FcεRI as an autoallergic target of IgE (autoallergen) in the complex pathophysiological scenario of CSU. The co-occurrence of anti-FcεRI IgG and IgE autoantibodies was documented only in late- and non-responders, but not in early ones, crediting the co-existence of autoimmune and autoallergic mechanisms as a driver of late/poor response to omalizumab. Full article