Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.

Effect of bariatric surgery on glycemic profiles in multiethnic obese nondiabetic Asians.

BACKGROUND: The effect of bariatric surgery on improvement and remission of type 2 diabetes (T2D) is well studied. The effect of surgery on glycemic profiles of obese, but nondiabetic individuals is unknown. OBJECTIVES: We aimed to study changes in glycemic indices in obese nondiabetics undergoing bariatric surgery and correlate fat mass loss with changes in glycemic profiles. SETTING: University Hospital, Singapore. METHODS: A prospective database of nonT2D patients who underwent bariatric surgery between April 2009 and December 2014 was analyzed. Changes in weight, fat mass, and glycemic profiles, including glycated hemoglobin, C-peptide levels, and the homeostasis model assessment of insulin resistance were studied at 1- and 3-year follow-up. RESULTS: One hundred thirty-three nondiabetics underwent bariatric surgery in the study period. Twenty-nine (21.8%) patients were found to have impaired fasting glycemia. We observed reductions in mean fat mass from 47.4 ± 12.2 kg preoperatively to 27.8 ± 11.6 kg at 1 year. Despite mean fat mass regain to 33.9 ± 19.6 kg at 3 years, homeostasis model assessment of insulin resistance improved from severe insulin resistant state of >5.00 (7.13 ± 11.5) preoperatively to normal ranges of <3.00 (1.55 ± .91) at 3 years. CONCLUSION: Bariatric surgery results in significant sustained weight loss in obese nondiabetics and normalizes glycated hemoglobin and homeostasis model assessment of insulin resistance after surgery. It is a promising modality to prevent or delay the onset of T2D in obese nondiabetic patients. Further studies should be conducted in nondiabetics to assess the efficacy of bariatric surgery in prevention of T2D onset in the longer term.

Effect of Maotai liquor in inducing metallothioneins and on hepatic stellate cells.

AIM: To explore the possible mechanism why drinking Maotai liquor dose not cause hepatic fibrosis. METHODS: After being fed with Maotai for 56 days consecutively, the male SD rats were decollated for detecting the biological indexes, and the livers were harvested to examine the liver indexes and the level of hepatic metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen generation were also observed. RESULTS: Hepatic MT contents were 216.0 ng.g(-1)+/-10.8 ng.g(-1) in the rats of Maotai group and 10.0 ng.g(-1)+/-2.8 ng.g(-1) in the normal control group, which was increased obviously in Maotain group (P<0.05). In the rats with grade CCL(2) poisoning induced by Maotai, hepatic MT content was 304.8 ng.g(-1)+/-12.1 ng.g(-1) whereas in the controls with grade CCL(4) poisoning, it was 126.4 ng.g(-1)+/-4.8 ng.g(-1) (P<0.05). MDA was 102.0 nmol.g(-1)+/-3.4 nmol.g(-1) in Maotai group and 150.8 nmol.g(-1)+/-6.7 nmol.g(-1) in the control group (P<0.05). When both of the groups were suffering from grade CCL(4) poisoning, hepatic MT contents was negatively correlated with MDA (r=-0.8023, n=20, P<0.01). The 570 nmA values of each tube with HSC regeneration at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai were 0.818, 0.742, 0.736, 0.72, 0.682, and 0.604, respectively. From the concentration of 10 g.L(-1), Maotai began to show obvious inhibitory effects against HSC, and the inhibition was concentration-dependent (P<0.05, P<0.01). Type I collagen contents in HSC were 61.4, 59.9, 50.1, 49.2, 48.7, 34.4 microg.g(-1) at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai. At the concentration of 100-200 g.L(-1), Maotai had obvious inhibitory effect against the secretion of type I collagen (P<0.05). Gene expression analysis was conducted on cells with Maotai concentrations of 0, 50, 100g.L(-1) respectively and the ash values of beta-actin gene expression were 0.88, 0.74, and 0.59, respectively,suggesting that at the concentration of 100g.L(-1), Maotai could obviously inhibit gene expression of type I procollagen (P<0.05), but the effect was not obvious at the concentration of 50 g.L(-1) (P>0.05). At the concentration of 10 g.L(-1), HSC growth in vitro inhibition rates were 16.4+/-2.3 in Maotai group and -8.4+/-2.3 in the control group (P<0.05). CONCLUSION: Maotai liquor can increase metallothioneins in the liver and inhibit the activation of HSC and the synthesis of collagen in many aspects, which might be the mechanism that Maotai liquor interferes in the hepatic fibrosis.