Vaccine-induced immune thrombotic thrombocytopenia following AstraZeneca (ChAdOx1 nCoV-19) vaccine: report of two cases

Vaccination with ChAdOx1 nCoV-19 can result in vaccine-induced immune thrombotic thrombocytopenia (VITT). This phenomenon mimics heparin-induced thrombocytopenia, yet it does not require heparin as a trigger. This case report highlights the potentially lifethreatening complication associated with ChAdOx1 nCov-19 vaccine, clinical presentation, diagnostic approach, and treatment. We report two cases of vaccine-induced immune thrombotic thrombocytopenia after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. We attribute these thrombotic conditions to the vaccine due to the remarkable temporal relationship. The proposed mechanism of VITT is a production of antibodies against platelet factor-4 resulting in massive platelet activation. Healthcare providers should be aware of the possibility of such a fatal complication, and the vaccine recipients should be warned about the symptoms of VITT

Serum IL-21 levels from celiac disease patients correlates with anti-tTG IgA autoantibodies and mucosal damage

Objectives: Coeliac disease is a multifactorial disorder influenced by environmental, genetic and immunological factors. Interleukin (IL)-21 has been linked to an increase disease risk and the serum level of IL-21 seems to be increased in CD compared to a healthy control population. Methods: Sera were collected from 160 CD patients, 120 untreated and 40 following a gluten-free diet, and form 45 healthy subjects. Serum IL-21 was evaluated by specific ELISA tests. Results: Our data show that patients with untreated CD display IL-21 concentrations significantly higher than both treated-CD patients (following a gluten-free diet) and controls. In addition, serum IL-21 correlates with serum titres of anti-tTG IgA autoantibodies. Finally, our results show a correlation of this cytokine with duodenal mucosal damage. Conclusions: A role of gluten, as antigen with stimulatory function on IL-21 production, seems to be confirmed by the longitudinal analyses showing that the gluten-free diet decreases to a nearly undetectable amount this cytokine. In addition, the finding of a positive correlation between the serum amount of IL-21 and the grade of duodenal mucosa damage suggests a strong immunomodulatory effect of this cytokine on cytotoxic T lymphocyte functions. This study provides an extra evidence to emerging data on the potential role IL-21 in CD pathogenesis, suggesting its involvement in the development and progression of CD. Significance statement: In untreated CD, serum IL-21 shows higher levels compared with treated CD and healthy subjects. Serum amounts of IL-21 correlate with anti-tTG IgA autoantibodies and with duodenal mucosa damage

Integrins α6Aβ1 and α6Bβ1 Promote Different Stages of Chondrogenic Cell Differentiation

The differentiation of chondrocytes and of several other cell types is associated with a switch from the alpha(6B) to the alpha(6A) isoform of the laminin alpha(6)beta(1) integrin receptor. To define whether this event plays a functional role in cell differentiation, we used an in vitro model system that allows chick chondrogenic cells to remain undifferentiated when cultured in monolayer and to differentiate into chondrocytes when grown in suspension culture. We report that: (i) upon over-expression of the human alpha(6B), adherent chondrogenic cells differentiate to stage I chondrocytes (i.e. increased type II collagen, reduced type I collagen, fibronectin, alpha(5)beta(1) and growth rate, loss of fibroblast morphology); (ii) the expression of type II collagen requires the activation of p38 MAP kinase; (iii) the over-expression of alpha(6A) induces an incomplete differentiation to stage I chondrocytes, whereas no differentiation was observed in alpha(5) and mock-transfected control cells; (iv) a prevalence of the alpha(6A) subunit is necessary to stabilize the differentiated phenotype when cells are transferred to suspension culture. Altogether, these results indicate a functional role for the alpha(6B) to alpha(6A) switch in chondrocyte differentiation; the former promotes chondrocyte differentiation, and the latter is necessary in stabilizing the differentiated phenotype