St George's, University of London, Cranmer Terrace, Tooting, London SW17 0RE, United Kingdom.
Med Hypotheses. 2018 Mar;112:24-26. doi: 10.1016/j.mehy.2018.01.008. Epub 2018 Jan 17.
The small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis are associated with autoantibodies to neutrophil cytoplasm antigens (ANCA), principally proteinase-3 (PR3) and myeloperoxidase (MPO). There is an association between GPA and nasal carriage of Staphylococcus aureus. The recent finding that S. aureus produces proteins that bind tightly to and block the function of both PR3 and MPO suggests a mechanism for ANCA formation. The bacterial protein-autoantigen conjugate is recognised by B cells with ANCA specificity, internalised, and the bacterial protein processed and presented to T cells with specificity for bacterial peptides. The T cell can then provide help to the B cell, allowing class switching, affinity maturation and the production of pathogenic ANCA. This mechanism predicts that T cells with this specificity will be found in patients, and that the bacterial protein-autoantigen conjugate will be particularly efficient at eliciting ANCA production.
小血管血管炎肉芽肿性多血管炎（GPA）和显微镜下多血管炎与抗中性粒细胞胞质抗体（ANCA）有关，主要是蛋白酶 3（PR3）和髓过氧化物酶（MPO）。GPA 与金黄色葡萄球菌鼻腔携带有关。最近的发现表明，金黄色葡萄球菌产生的蛋白质可以紧密结合并阻断 PR3 和 MPO 的功能，这为 ANCA 的形成提供了一种机制。细菌蛋白-自身抗原结合物被具有 ANCAs 特异性的 B 细胞识别，内化，并将细菌蛋白加工并呈递给特异性针对细菌肽的 T 细胞。然后，T 细胞可以为 B 细胞提供帮助，允许类别转换、亲和力成熟和产生致病性 ANCAs。该机制预测，患者中会发现具有这种特异性的 T 细胞，并且细菌蛋白-自身抗原结合物将特别有效地引发 ANCAs 的产生。
