Objectives

The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA).

Method

Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay.

Results

Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs.

Conclusion

Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.

中文翻译：

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抗氧化型II型胶原的免疫球蛋白A抗体可作为类风湿关节炎对脊椎关节炎进行分层的潜在生物标记。

目标

患病组织特异性新抗原的发现为开发重要的疾病组织特异性生物标志物提供了机会，这些标志物有助于疾病的预测，诊断和分层。对于没有诊断性生物标志物的自身免疫性疾病，这一机会特别重要。炎性自身免疫性疾病通常与局部产生大量反应性氧化剂有关。我们之前已经确定了类风湿性关节炎（RA）和1型糖尿病中引起免疫反应的氧化后翻译修饰（oxPTM）组织特异性新抗原。在本研究中，我们研究了脊椎关节炎（SpA）患者中oxPTM II型胶原（CII）抗体的存在及其临床意义。

方法

通过酶联免疫吸附法评估对天然CII和oxPTM-CII特异的抗体水平。

结果

分别在患有轴向性脊柱关节炎（axSpA），RA和银屑病关节炎（PsA）的患者的血清样本中观察到了与oxPTM-CII结合的免疫球蛋白G（IgG）。重要的是，虽然在axSpA和PsA患者中检测到强IgA抗oxPTM-CII反应，分别具有47％和84％的结合剂，但在RA患者中未检测到IgA抗oxPTM-CII。用生物制剂治疗的axSpA患者中的IgA抗oxPTM-CII反应性更高，更频繁，与使用合成疾病缓解性抗风湿药治疗的患者中9％的粘合剂相比，具有85％的粘合剂。

结论

我们的数据表明，SpA和PsA与oxPTM-CII抗体的存在有关，表明可能存在体液成分，可能使SpA患者与RA区别开来。我们的方法可能适用于其他疾病，尤其是炎性自身免疫性疾病。