Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in infliximab- and vedolizumab-treated patients

We report SARS-CoV-2 vaccine-induced immunity and risk of breakthrough infections in patients with inflammatory bowel disease treated with infliximab, a commonly used anti-TNF drug and those treated with vedolizumab, a gut-specific antibody targeting integrin a4b7 that does not impact systemic immunity. In infliximab-treated patients, the magnitude of anti-SARS-CoV2 antibodies was reduced 4-6-fold. One fifth of both infliximab- and vedolizumab-treated patients did not mount a T cell response. Antibody half-life was shorter in infliximab-treated patients. Breakthrough SARS-CoV-2 infections occurred more frequently in infliximab-treated patients and the risk was predicted by the level of antibody response after second vaccine dose. Overall, recipients of two doses of the BNT162b2 vaccine had higher anti-SARS-CoV-2 antibody concentrations, higher seroconversion rates, shorter antibody half-life and less breakthrough infections compared to ChAdOx1 nCoV-19 vaccine recipients. Irrespective of biologic treatment, higher, more sustained antibody levels were observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Patients treated with anti-TNF therapy should be offered third vaccine doses.

Study on the relationship of cPLA2, CK-MB, and membrane phospholipid content in acute myocardial infarction.

Increased plasma creatine kinase-myoglobin (CK-MB) occurs in patients with acute myocardial infarction (AMI), but its underlying relationship with cytosolic phospholipase A2 (cPLA2) is poorly understood. In the present study we sought to determine cPLA2 activation and its relationship with plasma and myocardial CK-MB level and membrane phospholipids (PLs) in an animal model of AMI. AMI was induced in 60 male Sprague-Dawley rats by ligating the left anterior descending of coronary artery. Rats were randomized into six groups at 0 (sham group), 1, 2, 4, 6, and 12 h after AMI onset (ten rats in each group). cPLA2 was detected by reverse transcription polymerase chain reaction and immunohistochemical staining for mRNA and protein expression, respectively. Plasma and myocardial CK-MB activity were measured by inhibition kinetics, and membrane PLs were determined by phosphorus quantitative method. Myocardial cPLA2 expression increased from 1 h and reached a peak at 2 h after AMI onset (p < 0.01) followed by a decrease but still remained high, whereas plasma CK-MB significantly increased in rats from 4 h after the onset of AMI (p < 0.05). During the first 6 h of AMI, a negative correlation existed between myocardial cPLA2 and membrane PLs (r = -0.504, p < 0.01), whereas myocardial cPLA2 levels were positively associated with plasma CK-MB (r = 0.741, p < 0.01) but negatively correlated with myocardial CK-MB in AMI groups (r = -0.785, p < 0.01). Myocardial cPLA2 level increased and is positively correlated with plasma CK-MB activity and negatively correlated with membrane phospholipid content in AMI rats at early stage.

Simvastatin inhibits sPLA2 IIa expression in aorta and myocardium.

BACKGROUND AND AIMS: Group IIa secretory phospholipase A2 (sPLA2 IIa) induces atherosclerosis by altering systemic lipoprotein mechanism. The aim of this study was to investigate the expression and localization of sPLA2 IIa in atherosclerosis of rat aorta, myocardium and visceral adipose tissue (VAT) and to explore the effect of simvastatin on sPLA2 IIa expression. METHODS: Thirty male Wistar rats were randomly divided into three groups: control group, test group, and simvastatin group. Control group rats were fed with standard chow, whereas those in the test group were fed with a high cholesterol diet. Simvastatin (5 mg/kg/day per gavage) was given to the rats in simvastatin group in addition to the high cholesterol diet. At the end of 8 weeks, rats were sacrificed and sPLA2 IIa measured by immunocytochemistry. RESULTS: sPLA2 IIa was present in smooth muscle cells, aortic plaques, and also in myocardium and VAT. In addition, sPLA2 IIa expression in myocardium and aorta was much higher in the test group than in control group (p <0.01). However, expression of the enzyme in myocardium and aorta was significantly decreased in the simvastatin group compared to the test group (p <0.05). Immunostaining of sPLA2 IIa was also present in VAT, but no significant changes were found in levels of this enzyme among the three groups (p >0.05). CONCLUSIONS: Myocardium and VAT may be two other important sources of sPLA2 IIa. Our data support the hypothesis that sPLA2 IIa may play a significant role in the pathogenesis of atherosclerosis. Simvastatin may reduce the process of atherosclerosis by decreasing the expression level of sPLA2 IIa in myocardium and aorta.