Chronic inflammation and extracellular matrix-specific autoimmunity following inadvertent periarticular influenza vaccination.
Adult
Autoimmunity
Chronic Disease
Extracellular Matrix
/ metabolism
Female
Genetic Predisposition to Disease
HLA-DRB1 Chains
/ genetics
Heparan Sulfate Proteoglycans
/ immunology
Histocompatibility Testing
Humans
Inflammation
/ immunology
Influenza Vaccines
/ immunology
Influenza, Human
/ immunology
Joint Capsule
/ immunology
Male
Orthomyxoviridae
/ physiology
Osteoclasts
/ immunology
Receptor Activator of Nuclear Factor-kappa B
/ metabolism
T-Lymphocytes
/ immunology
Tartrate-Resistant Acid Phosphatase
/ blood
Vaccination
/ adverse effects
Young Adult
Activation
Adverse event
Autoimmunity
B cells
Bone erosion
Bursitis
Extracellular matrix
HSPG
Immune response
Influenza vaccination
Plasmablast
RANK-L
SIRVA
Selfreactive
Shoulder injury
T cells
T follicular helper cells
TRAP5b
Ultrasound
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
18
05
2021
revised:
27
07
2021
accepted:
05
08
2021
pubmed:
18
8
2021
medline:
11
3
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34403915
pii: S0896-8411(21)00122-0
doi: 10.1016/j.jaut.2021.102714
pii:
doi:
Substances chimiques
HLA-DRB1 Chains
0
HLA-DRB1*04 antigen
0
Heparan Sulfate Proteoglycans
0
Influenza Vaccines
0
Receptor Activator of Nuclear Factor-kappa B
0
ACP5 protein, human
EC 3.1.3.2
Tartrate-Resistant Acid Phosphatase
EC 3.1.3.2
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102714Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.