Chronic inflammation and extracellular matrix-specific autoimmunity following inadvertent periarticular influenza vaccination

Julia R. Hirsiger, Giorgio Tamborrini, Dorothee Harder, Glenn R. Bantug, Gideon Hoenger, Mike Recher, Christian Marx, Quan Zhen Li, Ivan Martin, Christoph Hess, Arnaud Scherberich, Thomas Daikeler, Christoph T. Berger

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Viral infections may trigger autoimmunity in genetically predisposed individuals. Immunizations mimic viral infections immunologically, but only in rare instances vaccinations coincide with the onset of autoimmunity. Inadvertent vaccine injection into periarticular shoulder tissue can cause inflammatory tissue damage (‘shoulder injury related to vaccine administration, SIRVA). Thus, this accident provides a model to study if vaccine-induced pathogen-specific immunity accompanied by a robust inflammatory insult may trigger autoimmunity in specific genetic backgrounds. Methods: We studied 16 otherwise healthy adults with suspected SIRVA occurring following a single work-related influenza immunization campaign in 2017. We performed ultrasound, immunophenotypic analyses, HLA typing, and influenza- and self-reactivity functional immunoassays. Vaccine-related bone toxicity and T cell/osteoclast interactions were assessed in vitro. Findings: Twelve of the 16 subjects had evidence of inflammatory tissue damage on imaging, including bone erosions in six. Tissue damage was associated with a robust peripheral blood T and B cell activation signature and extracellular matrix-reactive autoantibodies. All subjects with erosions were HLA-DRB1*04 positive and showed extracellular matrix-reactive HLA-DRB1*04 restricted T cell responses targeting heparan sulfate proteoglycan (HSPG). Antigen-specific T cells potently activated osteoclasts via RANK/RANK-L, and the osteoclast activation marker Trap5b was high in sera of patients with an erosive shoulder injury. In vitro, the vaccine component alpha-tocopheryl succinate recapitulated bone toxicity and stimulated osteoclasts. Auto-reactivity was transient, with no evidence of progression to rheumatoid arthritis or overt autoimmune disease. Conclusion: Vaccine misapplication, potentially a genetic predisposition, and vaccine components contribute to SIRVA. The association with autoimmunity risk allele HLA-DRB1*04 needs to be further investigated. Despite transient autoimmunity, SIRVA was not associated with progression to autoimmune disease during two years of follow-up.

Original languageEnglish (US)
Article number102714
JournalJournal of Autoimmunity
StatePublished - Nov 2021


  • Activation
  • Adverse event
  • Autoimmunity
  • B cells
  • Bone erosion
  • Bursitis
  • Extracellular matrix
  • HSPG
  • Immune response
  • Influenza vaccination
  • Plasmablast
  • RANK-L
  • Selfreactive
  • Shoulder injury
  • T cells
  • T follicular helper cells
  • TRAP5b
  • Ultrasound

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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