Giuseppe Ercoli, Hugh Selway-Clarke, Dena Truijen, Milda Folkmanaite, Tate Oulton, Caitlin Norris-Grey, Rie Nakajima, Philip Felgner, Brendan W Wren, Kevin Tetteh, Nicholas J Croucher, Maria Leandro, Geraldine Cambridge, Jeremy S Brown
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引用次数: 0
Abstract
Objectives
Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B-cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array.
Methods
IgG responses to S. pneumoniae were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole-cell ELISA, a flow cytometry opsonisation assay and an S. pneumoniae protein array. For the RA patients, results were compared before and after B-cell depletion therapy.
Results
Compared to a well-characterised disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple S. pneumoniae protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen-specific responses also correlated with reduced IgG opsonisation of S. pneumoniae. Although B-cell depletion therapy with rituximab did not reduce overall IgG recognition of S. pneumoniae in the RA group, it was associated with marked disruption of pre-existing IgG repertoire to protein antigens in individual patients.
Conclusion
These data show RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA.
目的 类风湿性关节炎(RA)患者对感染的易感性增加,其中包括由肺炎链球菌引起的感染。目前尚不清楚 RA 为什么会增加对肺炎链球菌的易感性。本研究旨在使用新型蛋白质阵列评估 RA 和 B 细胞耗竭疗法对 289 种肺炎链球菌蛋白质抗原的天然抗体反应的影响。 方法 采用全细胞酶联免疫吸附试验、流式细胞仪抗溶血试验和肺炎双球菌蛋白阵列分析 RA 患者和疾病对照组(肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS))血清中肺炎双球菌 IgG 反应的特征。对 RA 患者进行了 B 细胞耗竭治疗前后的结果比较。 结果 与特征明确的疾病对照组 ME/CFS 患者相比,RA 患者对多种肺炎双球菌蛋白抗原的抗体反应减弱,对大约一半抗原的 IgG 识别率明显下降,同时这些反应的中位强度也有所降低。多种阵列抗原特异性反应的降低还与肺炎双球菌的IgG蛋白溶解度降低有关。虽然使用利妥昔单抗的 B 细胞耗竭疗法并未降低 RA 组对肺炎双球菌的总体 IgG 识别率,但却明显破坏了个别患者对蛋白质抗原的原有 IgG 反应谱系。 结论 这些数据表明,RA 与对肺炎双球菌的自然获得性适应性免疫的严重破坏有关,这种破坏可通过蛋白抗原阵列进行快速评估,并可能导致 RA 患者肺炎发病率的增加。
期刊介绍:
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.