Reports of Guillain-Barre Syndrome Following COVID-19 Vaccination in the USA: An Analysis of the VAERS Database.

BACKGROUND AND PURPOSE: An association between Guillain-Barre syndrome and its variants (GBS/V) and vaccines has led to hesitancy toward vaccination. COVID-19 vaccines could theoretically provoke GBS/V via immune activation. We analyzed reports of GBS/V after COVID-19 vaccination in the vaccine adverse event reporting system (VAERS). METHODS: The VAERS database is a surveillance system used to report vaccination events in the USA, and is open for consumers and physicians to access. It was queried for reports of GBS/V following COVID-19 vaccination. Reports were reviewed by four neurologists. Modified diagnostic criteria were used to classify reports into definite, possible, and not GBS/V or insufficient data. Descriptive statistics were used to describe the sample, chi-square tests and one-way ANOVAs were used to compare intergroup differences, and t-test were used to compare group means. RESULTS: In 2021, 815 reports of GBS/V were filed. The completion rate for the variables in VAERS was 93.5%. The median age was 55 years (interquartile range [IQR]=5-86 years) and 50% of the subjects were male. The median time of onset was 10 days (IQR=0-298 days), 11% reported onset on the day of vaccination, and 13% reported onset after 6 weeks. Hospitalization was reported by 77%, with a median stay of 7 days (IQR=1-150 days). Lack of recovery, permanent disability, and death constituted 57%, 46%, and 2% of the reports, respectively. Based on GBS/V criteria, 47% of the cases were definite, 16% were possible, and 37% were not GBS/V or insufficient data. An alternate diagnosis was provided in 9% of cases. CONCLUSIONS: GBS/V reports following COVID-19 vaccination were common, but many occurred outside of the expected timelines for GBS/V. Only 47% of cases represented definite GBS/V.

Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus.

C57BL/6 mice bearing the Sle2(z) lupus-susceptibility congenic interval on chromosome 4 display high titers of polyclonal autoantibodies with generalized B cell hyperactivity, hallmarks of systemic lupus erythematosus. In B6.Sle2(z)HEL(Ig).sHEL BCR-transgenic mice, Sle2(z) did not breach central tolerance, but it led to heightened expression of endogenous Ig H and L chains in splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval generated through recombinant mapping, was found to be upregulated in Sle2(z) B cells by microarray analysis, Western blot, and functional assays. Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice. These studies indicate that increased peripheral BCR revision, or selective peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate this process.

Modulating proximal cell signaling by targeting Btk ameliorates humoral autoimmunity and end-organ disease in murine lupus.

INTRODUCTION: Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity. The aim of this study was to determine the effect of Btk inhibition by PCI-32765 on the development of lupus in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice. METHODS: B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either the Btk inhibitor PCI-32765 or vehicle for 56 days. Following treatment, mice were examined for clinical and pathological characteristics of lupus. The effect of PCI-32765 on specific cell types was also investigated. RESULTS: In this study, we report that Btk inhibition dampens humoral autoimmunity in B6.Sle1 monocongenic mice. Moreover, in B6.Sle1.Sle3 bicongenic mice that are prone to severe lupus, Btk inhibition also dampens humoral and cellular autoimmunity, as well as lupus nephritis. CONCLUSIONS: These findings suggest that partial crippling of cell signaling in B cells and antigen presenting cells (APCs) may be a viable alternative to total depletion of these cells as a therapeutic modality for lupus.