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.

中文翻译：

---

意外的关节周围流感疫苗接种后的慢性炎症和细胞外基质特异性自身免疫

背景

病毒感染可能会引发遗传易感个体的自身免疫。免疫在免疫学上模仿病毒感染，但仅在极少数情况下，疫苗接种与自身免疫的发作同时发生。无意中将疫苗注射到关节周围的肩部组织会导致炎症性组织损伤（“与疫苗接种相关的肩部损伤，SIRVA）。因此，这次事故提供了一个模型来研究疫苗诱导的病原体特异性免疫是否伴随着强烈的炎症损伤可能引发特定遗传背景下的自身免疫。

方法

我们研究了 16 名健康成人，他们在 2017 年进行了一次与工作相关的流感免疫接种活动后出现疑似 SIRVA。我们进行了超声、免疫表型分析、HLA 分型以及流感和自身反应性功能免疫测定。在体外评估了疫苗相关的骨毒性和 T 细胞/破骨细胞相互作用。

发现

16 名受试者中有 12 名在成像时有炎症组织损伤的证据，其中 6 名受试者有骨侵蚀。组织损伤与强大的外周血 T 和 B 细胞激活特征以及细胞外基质反应性自身抗体相关。所有患有糜烂的受试者均为 HLA-DRB1*04 阳性，并显示出针对硫酸乙酰肝素蛋白聚糖 (HSPG) 的细胞外基质反应性 HLA-DRB1*04 限制性 T 细胞反应。抗原特异性 T 细胞通过 RANK/RANK-L 有效激活破骨细胞，并且破骨细胞激活标志物 Trap5b 在糜烂性肩部损伤患者的血清中含量较高。在体外，疫苗成分 α-生育酚琥珀酸酯概括了骨毒性并刺激了破骨细胞。自身反应是短暂的，没有证据表明进展为类风湿性关节炎或明显的自身免疫性疾病。

结论

疫苗误用、潜在的遗传易感性和疫苗成分会导致 SIRVA。与自身免疫风险等位基因 HLA-DRB1*04 的关联需要进一步研究。尽管存在短暂的自身免疫，但在两年的随访期间，SIRVA 与进展为自身免疫性疾病无关。