Rao, Sameer

ABSTRACT Background and Aims Alpha‐gal syndrome (AGS) is an IgE‐mediated hypersensitivity to galactose‐α‐1,3‐galactose, triggered by tick bites. It typically presents with delayed onset allergic or gastrointestinal symptoms after red meat consumption. This study aims to evaluate the prevalence of clinical symptoms and outcomes in AGS patients. Methods A systematic search of PubMed, Embase, and Cochrane Central was conducted to identify studies with at least five AGS patients that utilized alpha‐gal IgE for diagnosis and reported symptomatology. A random‐effects model calculated pooled prevalence and 95% confidence intervals (CIs) for clinical characteristics of AGS. Results Of the 739 studies screened, 15 met the inclusion criteria, comprising 1162 AGS patients (57% female). Urticaria was identified as the most prevalent symptom (63.8%, CI: 34.5–88.3, I 2 = 98.8%). At least one gastrointestinal symptom was reported in 69.2% of patients (CI: 49.3–85.9, I 2 = 97.5%), including abdominal pain (58.3%, CI: 36.0–78.9, I 2 = 96.0%), diarrhea (41.7%, CI: 22.3–62.5, I 2 = 93.4%), nausea (39.1%, CI: 29.2–49.6, I 2 = 79.1%), and vomiting (31.1%, CI: 21.9–41.2, I 2 = 70.4%). Tick bite history was recalled by 78.7% (CI: 46.4–98.1; I 2 = 99.1%), and 91.8% (CI: 84.6–96.8; I 2 = 70.3%) had symptom onset ≥ 1 h post red meat intake. Symptomatic improvement was observed in 86.5% (CI: 73.9–95.4, I 2 = 80.9%) of patients, with complete resolution in 42.7% (CI: 26.4–59.8, I 2 = 73.8%). Conclusion AGS typically presents with delayed onset allergic and GI symptoms after red meat intake, often with tick bite history. Majority of patients report symptomatic improvement on follow‐up.

Purpose of review Proteases constitute a group of enzymes that hydrolyze peptide bonds. Intestinal proteases are an integral part of gut homeostasis and digestion. This review discusses the broader classification of proteases, regulation of proteolytic activity (PA) in the intestinal tract, and how dysregulation of intestinal proteases contributes to the pathophysiology of conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease. We also discuss recent advancements in therapeutic modulation that directly or indirectly target intestinal proteases and can be utilized to treat these illnesses. Recent findings Host and microbiota derived proteases have been associated with symptoms in subsets of patients with IBS, IBD and celiac disease. Elevated PA mediates barrier dysfunction, visceral hypersensitivity as well as immune activation and inflammation. Recent mechanistic studies have revealed the nature of disease-associated proteases and mechanisms regulating their activity, particularly those driven by the microbiota. Advancements in activity-based probes have allowed novel ways of in vivo imaging of PA. Newer strategies targeting proteases include monoclonal antibodies, engineered microbiota as well as specific protease inhibitors. Summary Significant progresses made in the detection as well as regulation of PA is likely to provide therapeutic advancements for gastrointestinal diseases.