Regarding the severe forms of the disease in which thromboinflammation is prominent, both endothelial cells and platelets might be affected by autoimmune reactions in addition to direct viral ...infection and cytokine-mediated activation 3,4. ...multiple anti-phospholipid antibodies have been detected in the blood of hospitalized patients in relation with the severity of the disease and the formation of neutrophil extracellular traps known to contribute to thrombotic events 5. ...anti-annexin A2 autoantibodies found in critically ill patients were suggested to contribute to small vessel damage in the lungs 7. Besides endothelial cell damage, activation of platelets is the other cornerstone of the prothrombotic state characteristic of COVID-19 4. Anti-PF4 antibodies would then recapitulate the sequence of events responsible for heparin-induced thrombocytopenia. Besides anti-PF4 autoantibodies, anti-phospholipid antibodies could also contribute to platelet activation as well as antiviral antibodies as observed in other infections 42,43.
The opinion I put forward in this paper is that attention must continue to be paid to clinical observations compatible with a detrimental effect of anti-SARS-CoV-2 in certain diseases of ...immunological nature. Using the example of the atypical thrombocytopenic thromboses caused by adenoviral-vector-based vaccines, I argue that usual post-marketing pharmacovigilance programs may fail in identifying very rare vaccine-related disorders. Since the robust protective immunity induced by mRNA vaccines is related to their distinct capacity to induce strong stimulation of T follicular helper cells, I suggest that the safety of mRNA vaccines should be further assessed by appropriately designed epidemiological and mechanistic studies focusing on lymphoproliferative and autoimmune diseases in which T follicular helper cells were found to play a key role.
Michel Goldman and colleagues call on the European medical and scientific community to coordinate efforts on immunotherapy-based approaches to coronavirus.
The 100th Anniversary of the Nobel Prize in Physiology or Medicine 1919 awarded to Jules Bordet offers the opportunity to underline the contributions of this Belgian doctor to the blooming of ...immunology at the end of the nineteenth century at the Institut Pasteur de Paris. It is also the occasion to emphasize his achievements as director of the Institut Pasteur du Brabant and professor at the Université libre de Bruxelles. Both in France and Belgium, he developed a holistic vision of immunology as a science at the crossroads of chemistry, physiology, and microbiology.
Interleukin-12p70 (IL-12p70) induces T-helper-1-cell responses and IL-23, a related cytokine, is the master switch in several T-cell-mediated inflammatory disorders. IL-27, another member of the ...IL-12 family, regulates innate and adaptive immune responses. Recently, distinct combinations of transcription factors have been shown to regulate the expression of the genes that encode these three cytokines. Toll-like receptor ligands, in association with other microbial products and endogenous mediators, tip the balance between the expression of IL-12 family members and thereby may control the outcome of T-cell-mediated inflammation. On this basis, we present a novel perspective on the pathogenesis and regulation of inflammatory disorders.
Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this ...cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL.
In myeloid dendritic cells, activation of the IL-27p28 gene is selectively induced by ligands of TLR4 or TLR3, both coupled to the Toll/IL-1R-related domain-containing adaptor-inducing IFN/IFN ...regulatory factor (IRF)3 pathway. In response to both ligands, autocrine type 1 IFN production was required for optimal IL-27p28 expression. Type I IFN signaling was necessary for sustained IRF1 activation and formation of the IRF9-containing IFN-stimulated gene factor 3 complex. Indeed, we demonstrated that IRF1 and IRF9 are sequentially activated and recruited to the IL-27p28 IFN-stimulated regulatory element site. Involvement of IRF1 and IRF9 in the induction of IL-27p28 was confirmed in vitro and upon in vivo exposure to TLR ligands. Thus, in response to TLR4 or TLR3 ligation, the initial induction of the IL-27p28 gene depends on the recruitment of IRF1 and IRF3, whereas transcriptional amplification requires recruitment of the IFN-stimulated gene factor 3 complex. These results highlight the complex molecular interplay between TLRs and type I IFNs for the control of IL-27 synthesis.
Enlargement of axillary, supraclavicular or cervical lymph nodes following vaccination with COVID-19 mRNA vaccines is more frequent than initially reported, with a rate reaching up to 16% following ...the second dose of the Ivloderna mRNA vaccine. Although vaccine-related lymphadenopathy is most often a benign, self-resolving phenomenon, a few cases or B-cell- orT-cell-derived lymphoma were reported in the literature. There are also reports of clinico-pathological features suggestive of lymphoma but which ultimately proved to be caused by a non-malignant condition such as Epstein-Barr infection, extrapulmonary tuberculosis, or histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease). So far, these isolated observations did not receive much attention in the medical community as the causal relationship with the vaccine administration was not established. On the other hand, they raise concerns in the lay public, especially among patients with similar experiences.
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