Unique Serum Immune Phenotypes and Stratification of Oklahoma Native American Rheumatic Disease Patients.
Unique Serum Immune Phenotypes and Stratification of Oklahoma Native American Rheumatic Disease Patients.
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俄克拉荷马州美洲原住民风湿病患者的独特血清免疫表型和分层。
DOI：
10.1002/acr.24795
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发表时间：
2023
影响因子：
4.7
通讯作者：
James,JudithA
中科院分区：
文献类型：
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作者：
Slight-Webb,Samantha;Guthridge,CarlaJ;Kheir,Joseph;Chen,Hua;Tran,Ly;Gross,Tim;Roberts,Virginia;Khan,Sohail;Peercy,Michael;Saunkeah,Bobby;Guthridge,JoelM;James,JudithA
美洲原住民（NA）人群风湿性疾病的发病率较高，并存在重叠的疾病症状和非传统的血清学特征，因此迫切需要更好的生物标志物在NA诊断。这项研究使用机器学习方法来识别免疫特征，更有效地对风湿性疾病的NA患者进行分层。（RA; n = 28），自身抗体阴性（AAB−）RA（n = 18），全身性自身免疫性风湿病（n = 28），关节痛/骨关节炎（n = 28），或多关节炎/未分化结缔组织病（n = 28），对照患者（n = 28）提供血清样品用于细胞因子、趋化因子和AAB评估。随机森林聚类和可溶性介质组用于识别具有相似生物特征的患者和对照患者。美国大学的风湿病标准的具体系统性疾病和RA确定的疾病表现的差异across clusters.ResultsSerum可溶性介质是不同质的不同NA风湿性疾病诊断组之间，反映自身免疫性疾病的异质性。通过血清生物标志物的聚类产生了5种类似的免疫表型。与慢性炎症相关的可溶性介质和途径以及先天性、B细胞、T滤泡辅助细胞和干扰素相关途径的参与，沿着调节特征，区分了患者中的5种免疫特征。选择的临床特征与个体免疫特征相关。低炎症和较高的监管签名的患者更有可能有一些临床表现，而与T细胞通路参与有更多的arthrits.ConclusionSerum蛋白质签名区分NA患者与风湿性疾病到不同的免疫亚群。随着时间的推移，这些免疫特征可能有助于早期诊断，并有助于指导更个性化的治疗方法。
ObjectiveNative American (NA) populations have higher rates of rheumatic disease and present with overlapping disease symptoms and nontraditional serologic features, thus presenting an urgent need for better biomarkers in NA diagnostics. This study used a machine learning approach to identify immune signatures that more effectively stratify NA patients with rheumatic disease.MethodsAdult NA patients with autoantibody‐positive (AAB+) rheumatoid arthritis (RA; n = 28), autoantibody negative (AAB−) RA (n = 18), systemic autoimmune rheumatic disease (n = 28), arthralgia/osteoarthritis (n = 28), or polyarthritis/undifferentiated connective tissue disease (n = 28), and control patients (n = 28) provided serum samples for cytokine, chemokine, and AAB assessment. Random forest clustering and soluble mediator groups were used to identify patients and control patients with similar biologic signatures. The American College of Rheumatology criteria specific for systemic disease and RA identified differences in disease manifestations across clusters.ResultsSerum soluble mediators were not homogenous between different NA rheumatic disease diagnostic groups, reflecting the heterogeneity of autoimmune diseases. Clustering by serum biomarkers created 5 analogous immune phenotypes. Soluble mediators and pathways associated with chronic inflammation and involvement of the innate, B cell, T follicular helper cell, and interferon‐associated pathways, along with regulatory signatures, distinguished the 5 immune signatures among patients. Select clinical features were associated with individual immune profiles. Patients with low inflammatory and higher regulatory signatures were more likely to have few clinical manifestations, whereas those with T cell pathway involvement had more arthritis.ConclusionSerum protein signatures distinguished NA patients with rheumatic disease into distinct immune subsets. Following these immune profiles over time may assist with earlier diagnoses and help guide more personalized treatment approaches.