key: cord-0833020-37zteuvj
authors: Londoño, Maria-Carlota; Gratacós-Ginès, Jordi; Sáez-Peñataro, Joaquín
title: Another case of autoimmune hepatitis after SARS-CoV-2 vaccination. Still casualty?
date: 2021-06-12
journal: J Hepatol
DOI: 10.1016/j.jhep.2021.06.004
sha: ec5794b4a416f4139c05470874477d0a6d12998a
doc_id: 833020
cord_uid: 37zteuvj

nan

We read with interest the letter entitled "Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) Vaccine: Causality or casualty?" by Bril F. et al [1] . recently published in Journal of Hepatology. We had a similar case which strengthens the message of SARS-CoV-2 vaccines as a potential trigger for autoimmune hepatitis (AIH).

The patient is a 41-year-old female with past medical history of premature ovarian failure undergoing substitutive hormonal therapy with no side effects. After receiving the first dose of SARS-CoV-2 Moderna vaccine (mRNA-1273) the patient presented epigastric pain, nausea and vomiting. These symptoms lasted for 3 weeks, and then showed a decreased intensity. Seven days after the second dose, symptoms reappeared with higher intensity and were associated Specific environmental factors, including virus, drugs, herbal products, trigger the loss of selftolerance to liver autoantigens. Several reports have shown that vaccination against influenza and hepatitis A viruses can trigger AIH [3, 4] . The mechanism behind the development of vaccine-induced AIH is unknown but it is probably similar to that described for other autoimmune phenomena: genetic susceptibility, exposure to foreign peptides homologous to human peptides (molecular mimicry), and immune system stimulation by vaccine adjuvant [5] .

Moderna vaccine lacks of immune adjuvants but the presence of anti-SLA in our patient J o u r n a l P r e -p r o o f prompts us to investigate whether there was homology between the SARS-CoV-2 spike protein and soluble liver antigen. Using protein BLAST to align the sequence of these two proteins, we found no significant similarity. However, linear sequence matches in amino acid motifs is not the only criteria for molecular mimicry [6] and we cannot completely rule-out that other could have been involved in this case, such as: 1) similar native or glycosylated amino acid epitopes shared between the protein expressed in the host after vaccination and soluble liver antigen, and 2) structural similarities between the proteins [7] . It is also possible that other liver autoantigens (different from SLA) share sequence homology with the protein expressed by the host after SARS-CoV-2 vaccination with mRNA vaccines [8] .

Finally, we have to consider the specific features of mRNA vaccines. This approach is based on the synthesis of RNA coding for the desired antigenic protein, but in order to avoid the degradation, RNA is encapsulated in nanoparticles or liposomes that deliver their content inside the target cells by endocytosis. Prior translation, RNA binds to pattern recognition receptors (especially Toll-like receptors) resulting in the activation of several proinflammatory signals including type I interferon response [9] . The up-regulation of these pathways is similar to what has been described in AIH (and other autoimmune diseases) and therefore we believe that more that casualty, the association between SARS-CoV-2 vaccines and AIH is causality.

"One swallow does not make summer" and the benefits of vaccination are extremely higher than the potential risks of the vaccines and therefore the report of these two cases must not advice against vaccination. It should be noted that these reports illustrate a rare adverse event that has only been detected after the administration of millions of doses of mRNA vaccines at a "real-world" setting. Indeed, the coverage of the active surveillance monitoring program established in the hospitals, together with a close collaboration within medical departments, supported the detection of this rare adverse event and its association with previous vaccination.

Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?

Cellular and Molecular Mechanisms of Autoimmune Hepatitis

Autoimmune hepatitis following influenza virus vaccination: Two case reports

Hepatitis A vaccine associated with autoimmune hepatitis

Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction

Defining rules for the peptide-MHC class II interaction

Molecular mimicry and autoimmunity

Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine

Do COVID-19 RNA-based vaccines put at risk of immune-mediated diseases? In reply to "potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases