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.

Elena Pérez-Nadales and Belén Gutiérrez-Gutiérrez have contributed equally to this work.Investigators listed in Acknowledgments.

BackgroundIdentification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications. ObjectiveThis study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations. MethodsBiomarkers of T cell driven disease were compared between patients with L-HES versus idiopathic HES (I-HES) variants. Those performed routinely (serum immunoglobulin levels, T cell phenotyping, TCR gene rearrangement patterns) were collected from medical files, while others were prospectively assessed on stored blood samples (serum CCL17/TARC levels, in-vitro cytokine production). ResultsThis study included 48 patients with I-HES and 20 with L-HES associated with a CD3-CD4+ T cell subset, including 7 with less than 5% aberrant cells. Neither increased serum immunoglobulin levels nor clonal TCR gene rearrangements were sensitive or specific for L-HES. In contrast, systematically enhanced expression of the T cell surface antigens CD2, CD45RO, and CD95 by these cells allowed for accurate detection by flow cytometry. Serum CCL17/TARC levels were significantly higher in L-HES compared to I-HES patients, and a threshold of 3000 pg/ml allowed for detection of all subjects with L-HES with 75% specificity. Quantification of intracytoplasmic cytokine production by flow cytometry is the most reliable method for detection of enhanced type 2 cytokine expression, most notably for IL-4 and IL-13. ConclusionAdapting the standard of procedure for T cell phenotyping in patients with unexplained Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationhypereosinophilia is currently the most reliable means of identifying those with CD3-CD4+ L-HES.