WO2021120827A1 - 一种血清蛋白hfrep1在类风湿性关节炎疾病状态诊断中的应用 - Google Patents

一种血清蛋白hfrep1在类风湿性关节炎疾病状态诊断中的应用 Download PDF

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WO2021120827A1
WO2021120827A1 PCT/CN2020/122351 CN2020122351W WO2021120827A1 WO 2021120827 A1 WO2021120827 A1 WO 2021120827A1 CN 2020122351 W CN2020122351 W CN 2020122351W WO 2021120827 A1 WO2021120827 A1 WO 2021120827A1
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rheumatoid arthritis
hfrep1
diagnosis
remission
diagnostic
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French (fr)
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刘史佳
周伟
纪伟
谈文峰
郭云柯
柯梦颖
卢佳微
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江苏品升医学科技有限公司
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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/10—Musculoskeletal or connective tissue disorders
    • G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints

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  • the invention belongs to the field of disease detection and diagnosis, and relates to the application of biomarkers in disease diagnosis, and in particular to the application of a serum protein HFREP1 in rheumatoid arthritis disease state diagnosis.
  • Rheumatoid arthritis is a systemic autoimmune disease with erosive arthritis as the main manifestation.
  • the incidence rate in my country is 0.2%-0.4%, and it is more common in women.
  • the pathological manifestations are chronic inflammation of the synovium of the joints, formation of pannus, and destruction of the cartilage and bone of the joints, which ultimately leads to joint deformities and loss of function.
  • the current diagnosis of RA refers to the American College of Rheumatology (ACR) and the European Union against Rheumatism (EULAR).
  • EULAR recommends the RA disease activity score system (disease activity score in 28 joints, DAS28). According to this scoring system, the disease state of RA is divided into active period and remission period.
  • DAS28 scoring system is a set of subjective scoring system, which requires high doctor experience.
  • the present invention is proposed.
  • the application of a serum protein HFREP1 in preparing reagents or kits for diagnosing the disease state of rheumatoid arthritis refers to the active phase and the remission phase.
  • the serum protein HFREP1 diagnostic area classified rheumatoid arthritis in remission and active phase.
  • the area under the ROC curve AUC was as high as 0.9843, the sensitivity was 0.9412, and the specificity was 0.9667; in the validation set, the serum protein HFREP1 diagnostic area classified rheumatism
  • the accuracy of patients with arthritis in remission and active phase is as high as 97.62%. It can be seen that the serum protein HFREP1 has extremely high diagnostic value in the classification of active and remission stages of rheumatoid arthritis in the diagnostic area. The diagnostic accuracy is high. Compared with the existing DAS28 scoring system, it is objective and easy to operate.
  • the serum protein HFREP1 can be used for A diagnostic kit is prepared to classify the active stage and remission stage of rheumatoid arthritis in the diagnostic area.
  • Figure 1 shows the ROC curve of the HFREP1 diagnostic area in the test set to classify patients in remission and active phase of rheumatoid arthritis
  • Figure 2 shows the sample distribution of patients with rheumatoid arthritis in remission and active patients in the HFREP1 diagnostic area of the validation set.
  • Example 1 HFREP1 diagnostic area classification of the diagnostic efficacy of patients in remission and active phase of rheumatoid arthritis
  • Test set samples 34 patients with rheumatoid arthritis in remission and 30 patients with rheumatoid arthritis in active stage were collected from Jiangsu Provincial Hospital of Traditional Chinese Medicine. There was no significant difference in age, gender and body mass index matching between patients in remission and active stage;
  • Validation set samples 26 patients with rheumatoid arthritis in remission and 16 patients with rheumatoid arthritis in active stage were collected from Jiangsu Provincial People's Hospital. There was no significant difference in age, gender and body mass index matching between patients in remission and active stage.
  • the enrollment criteria for patients with rheumatoid arthritis in remission and active periods are as follows:
  • the highest score is selected for each part. If a patient has 5 small joints and 4 large joints involved, 3 points are awarded. The sum of the scores of the four parts is ⁇ 6 points, the diagnosis is made of RA.
  • the number of affected joints does not include the distal interphalangeal joints, the first carpal-metacarpal joint and the first metatarsophalangeal joint; the medium and large joints: double shoulder joints, double elbow joints, double hip joints, double knee joints and double ankle joints.
  • Small joints Except for the medium and large joints, the other joints that do not include the distal interphalangeal joints, the first carpal metacarpal joint, and the first metatarsophalangeal joint.
  • Low titer is defined as exceeding the upper limit of normal, but not higher than 3 times the upper limit of normal.
  • High titer is defined as exceeding 3 times the upper limit of normal.
  • DAS28 ⁇ 2.6 is the disease remission stage
  • DAS28>2.6 is the disease active stage
  • Exclusion criteria 1Does not meet the diagnostic criteria for rheumatoid arthritis and related diagnostic criteria for the active stage of RA. 2 Those who have taken western medicine or other drugs for treatment for a long time and cannot be stopped. 3 Overlap other rheumatism, such as systemic lupus erythematosus, Sjogren’s syndrome, severe osteoarthritis, etc. 4 Those with severe deformities or loss of labor. 5Patients with severe cardiopulmonary function or liver, kidney and hematopoietic system diseases. 6Women who are pregnant or breastfeeding. 7 Subjects or their family members are unwilling to participate in clinical trials. 8 Those who suffer from mental illness and cannot communicate normally.
  • Case rejection criteria 1For subjects with poor compliance; 2Those who did not take the study drug as prescribed by the doctor after the case was enrolled; 3Those who did not have any evaluable data after the case was enrolled.
  • HFREP1 ELISA kit was purchased from RayBiotech., Inc.
  • Group HFREP1 content ( ⁇ g/mL) Patients with active rheumatoid arthritis 10.31 ⁇ 16.47 Patients with rheumatoid arthritis in remission 0.60 ⁇ 0.42
  • the target protein diagnostic area classifies the ROC curve of patients with active and remission rheumatoid arthritis
  • the basic evaluation indexes of diagnostic tests include sensitivity, specificity, etc., and comprehensive evaluation indexes include Youden index, ROC, AUC, etc.
  • the ROC curve is based on the above-mentioned sensitivity and specificity. Take the possible diagnostic thresholds in the diagnostic test as the diagnostic point, and calculate the corresponding sensitivity and specificity according to the above table. Then, using sensitivity as the ordinate and 1-specificity as the abscissa, mark the sensitivity and specificity of each point at each diagnosis point in the coordinate chart, and connect the coordinate points to obtain a smooth curve, which is the ROC curve . The more and denser the diagnosis points are set, the smoother the ROC curve obtained.
  • the ROC curve uses each test result as a possible diagnostic threshold, and the area under the curve AUC indicates the accuracy of the diagnostic test.
  • the area under the ROC curve AUC has been generally recognized as an inherent accuracy indicator for the authenticity evaluation of diagnostic tests.
  • AUC is 0.5, there is no diagnostic significance; when AUC is 0.5 to 0.7, the diagnostic accuracy is low; AUC is 0.7 to 0.9 When, it means that the diagnosis accuracy is medium; when AUC>0.9, it means that the diagnosis has high accuracy.
  • HFREP1 protein (X) in the training set samples was used as the independent variable, and the group (i.e. patients with rheumatoid arthritis in remission and active period) was used as the dependent variable.
  • Metalogistic regression equation can be used to obtain the regression prediction probability p of each serum sample, use the possible regression prediction probability p as the diagnosis point, calculate the sensitivity and specificity, and draw the ROC curve (as shown in Figure 1), and the AUC is 0.9843 , The sensitivity is 0.9412, and the specificity is 0.9667.
  • Calculate the Widen index specificity+sensitivity-1 according to the coordinates of the ROC curve, and the predicted probability p value corresponding to the maximum value of the Widen index is the best cut- for patients with rheumatoid arthritis in remission vs. active stage that can be classified in the diagnostic area.
  • the off value is 0.511.
  • HFREP1 use the best cut-off value of HFREP1 to classify patients with rheumatoid arthritis in remission vs. active phase as the diagnostic threshold to predict the correctness of serum samples from patients with rheumatoid arthritis in remission vs. active phase.
  • the number of samples divided by the total number of samples is the accuracy of the target protein region to classify patients with rheumatoid arthritis in remission vs. active phase.
  • the accuracy of HFREP1 diagnosis area to classify patients with rheumatoid arthritis in remission vs. active phase is 97.62%.
  • the sample distribution diagram is shown in Figure 2.
  • the serum protein HFREP1 has extremely high diagnostic value in the classification of active and remission stages of rheumatoid arthritis in the diagnostic area.
  • the diagnostic accuracy is high.
  • Serum protein HFREP1 can be used for A diagnostic kit is prepared to classify the active stage and remission stage of rheumatoid arthritis in the diagnostic area.
  • Example 2 A kit for classifying the active stage and remission stage of rheumatoid arthritis in the diagnostic area
  • kits used to classify the active stage and remission stage of rheumatoid arthritis in the diagnostic area which includes an ELISA reagent for detecting the content of serum protein HFREP1.

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Abstract

一种血清蛋白HFREP1在类风湿性关节炎疾病状态诊断中的应用。根据欧洲抗风湿病联盟推荐的类风湿关节炎疾病活动性评分系统DAS28，RA的疾病状态被分为活动期和缓解期。但是，DAS28评分系统是一套主观评分系统，对医生的经验要求较高。血清蛋白HFREP1在诊断区分类风湿关节炎活动期和缓解期方面具有极高的诊断价值，诊断准确度高，比现有DAS28评分系统客观、易于操作，可以用于制备成诊断区分类风湿关节炎活动期和缓解期的诊断试剂盒。

Description

一种血清蛋白HFREP1在类风湿性关节炎疾病状态诊断中的应用
本申请要求于2019年12月20日提交中国专利局、申请号为201911322787.2、发明名称为“一种血清蛋白HFREP1在类风湿性关节炎疾病状态诊断中的应用”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明属于疾病检测诊断领域，涉及生物标志物在疾病诊断方面的应用，具体涉及一种血清蛋白HFREP1在类风湿性关节炎疾病状态诊断中的应用。
背景技术
类风湿关节炎(rheumatoid arthritis,RA)是一种以侵蚀性关节炎为主要表现的全身性自身免疫性疾病。我国发病率为0.2％-0.4％，以女性多发。病理表现为关节滑膜的慢性炎症、血管翳形成，并出现关节的软骨和骨破坏，最终导致关节畸形和功能丧失。目前RA的诊断参考美国风湿病学会(ACR)和欧洲抗风湿病联盟(EULAR)。EULAR推荐了RA疾病活动性评分系统(disease activity score in 28joints，DAS28)。根据该评分系统，RA的疾病状态被分为活动期、缓解期。
但是，DAS28评分系统是一套主观评分系统，对医生的经验要求较高。
为了提高RA疾病状态诊断的客观性，特提出本发明。
发明内容
本发明的目的是为了克服现有技术的不足，提供一种血清蛋白HFREP1在类风湿性关节炎疾病状态诊断中的应用。
本发明上述目的通过如下技术方案实现：
一种血清蛋白HFREP1在制备诊断类风湿性关节炎疾病状态的试剂或试剂盒中的应用，所述类风湿性关节炎疾病状态指活动期和缓解期。
在测试集中，血清蛋白HFREP1诊断区分类风湿性关节炎缓解期与活动期患者的ROC曲线下面积AUC高达0.9843，灵敏度为0.9412，特异性为0.9667； 在验证集中，血清蛋白HFREP1诊断区分类风湿性关节炎缓解期与活动期患者的准确度高达97.62％。由此可见，血清蛋白HFREP1在诊断区分类风湿关节炎活动期和缓解期方面具有极高的诊断价值，诊断准确度高，比现有DAS28评分系统客观、易于操作，可以将血清蛋白HFREP1用于制备成诊断区分类风湿关节炎活动期和缓解期的诊断试剂盒。
附图说明
图1为测试集中HFREP1诊断区分类风湿关节炎缓解期患者和活动期患者的ROC曲线；
图2为验证集中HFREP1诊断区分类风湿关节炎缓解期患者和活动期患者的样本分布图。
具体实施方式
下面结合附图和实施例具体介绍本发明实质性内容，但并不以此限定本发明的保护范围。
实施例1：HFREP1诊断区分类风湿关节炎缓解期患者和活动期患者的诊断效能
一、实验样本和试剂
测试集样本：收集江苏省中医院34例类风湿关节炎缓解期患者和30例类风湿关节炎活动期患者，缓解期患者和活动期患者的年龄、性别和体重指数匹配无显著差异；
验证集样本：收集江苏省人民医院26例类风湿关节炎缓解期患者和16例类风湿关节炎活动期患者，缓解期患者和活动期患者的年龄、性别和体重指数匹配无显著差异。
类风湿关节炎缓解期与活动期患者的入组标准如下：
参照2010年ACR和EULAR联合颁布的类风湿关节炎诊断标准：
Figure PCTCN2020122351-appb-000001
注：每一部分选取最高分。如一个患者有5个小关节和4个大关节受累，则得3分。四个部分所得分数之和≥6分，则确诊为RA。受累关节数不包括远端指间关节、第一腕掌关节及第一跖趾关节；中、大关节：双肩关节、双肘关节、双髋关节、双膝关节及双踝关节。小关节：除中、大关节外，且不包括远端指间关节、第一腕掌关节及第一跖趾关节的其余关节。低滴度定义为超过正常上限，但不高于3倍正常上限。高滴度定义为超过3倍正常上限。
类风湿性关节炎活动期判断标准(采用28个关节炎的疾病活动度(disease activity score，DAS28)：DAS28＜2.6为疾病缓解期；DAS28＞2.6为疾病活动期。
排除标准：①不符合类风湿关节炎病症诊断标准及RA活动期相关诊断标准。②长时间服用西药或者其他药物进行治疗而且不可以停用者。③重叠其他风湿病，如系统性红斑狼疮、干燥综合征、严重骨关节炎等。④伴有严重畸形疾病或者丧失劳动力者。⑤患者合并有严重心肺功能或者肝脏、肾脏以及造血系统等疾病者。⑥孕妇或者正处于哺乳期的妇女。⑦受试者本人或者家属不愿意参加临床试验者。⑧患有精神疾病不能够正常沟通者。
病例剔除标准:①对于依从性差的受试者；②病例入组后未按照医嘱服用研究药物者；③病例入组后无任何可评价数据者。
病例脱落标准:①发生严重不良事件、并发症不宜继续接受实验者；②实验过程中自行退出或失访者。控制受试者队列脱失<10％。
主要实验试剂：
HFREP1 ELISA试剂盒购买于RayBiotech.,Inc.
二、实验方法
1、血清样本的采集及储存
采集患者清晨空腹外周血并将其置于不含抗凝剂的试管内，在室温下自然凝集30-60min，待血液凝固，以2000rpm速度离心10min，小心吸取上层清亮血清液体于无菌冻干管中，标记后放入-80℃冰箱储存备用。
2、ELISA测定血清中目标蛋白的含量
严格按照ELISA试剂盒流程操作测定血清中HFREP1的含量。
3、数据处理方法
建立测试集中目标蛋白的ROC曲线，计算曲线下面积(AUC)及95％可信区间。运用Logistic回归建立回归方程，产生一组新变量logit[P]，经过logit[P]＝Ln [p/(1-p)]转换，得预测概率p，对该新变量进行ROC曲线分析。验证集中，以ROC曲线得到的最佳cut-off值为阈值计算目标蛋白对于类风湿性关节炎疾病状态的诊断准确度。
三、实验结果
1、目标蛋白在类风湿性关节炎疾病状态的丰度差异
在训练集中，与类风湿关节炎缓解期患者相比，活动期患者血清HFREP1的绝对含量显著上调，测定结果如下表所示。
组别 HFREP1含量(μg/mL)
类风湿性关节炎活动期患者 10.31±16.47
类风湿性关节炎缓解期患者 0.60±0.42
2、目标蛋白诊断区分类风湿性关节炎活动期与缓解期患者的ROC曲线
ROC曲线评价法的原理：
诊断试验的基本评价指标有敏感度、特异性等，综合评价指标有Youden指数、ROC、AUC等。对于诊断试验的评价，首先需要通过金标准知道待测样本的真实组别。对于按金标准确定的组别，相当于本项目的类风湿性关节炎活动期与缓解期患者，采用诊断试验检测的结果可以分为如下情况：
阳性(True Positive,TP)；诊断试验检测为阳性(与金标准结果一致)；
阴性(True Negative,TN)；诊断试验检测为阴性(与金标准结果一致)；
假阳性(False Positive,FP)：诊断试验检测为阳性(与金标准结果不一致)；
假阴性(False Negative,FN)：诊断试验检测为阴性(与金标准结果不一致)。
可以用下表表示：
Figure PCTCN2020122351-appb-000002
诊断试验的敏感度＝A/(A+C)；诊断试验的特异性＝D/(B+D)。通过敏感度和特异性可以得出诊断试验相对于金标准的诊断灵敏程度和特异程度。敏感度高代表将类风湿性关节炎缓解期诊断为阴性的个数少，漏诊率低；特异性高代表将类风湿性关节炎活动期诊断为阳性的个数少，误诊率低。
ROC曲线正是基于上述敏感度和特异性绘制出的曲线。以诊断试验中可能的诊断界值作为诊断点，根据上述表格计算出相应的敏感度和特异性。然后，以敏感度为纵坐标，1-特异性为横坐标，将各诊断点时各点的敏感度和特异性点在坐标图中标出，连接坐标点得到平滑曲线，该曲线即为ROC曲线。诊断点设置的越多越密，得到的ROC曲线就越平滑。
ROC曲线是以每一个检测结果作为可能的诊断界值，其曲线下面积AUC的大小表明了诊断试验准确度的大小。ROC曲线下面积AUC作为诊断试验真实性评价的固有准确度指标已被普遍认可，AUC为0.5时，即无诊断意义；AUC在0.5～0.7时，表示诊断准确率较低；AUC在0.7～0.9时，表示诊断准确性中等；AUC＞0.9时，表示诊断有较高的准确性。
HFREP1诊断区分类风湿性关节炎缓解期与活动期患者
以训练集样本中HFREP1蛋白(X)的含量作为自变量，以组别(即类风湿性关节炎缓解期与活动期患者)作为应变量，对目标蛋白在类风湿性关节炎缓解期与活动期患者血清样本中的含量进行二元逻辑回归，得到二元逻辑回归 方程：Ln [p/(1-p)]＝3.160X-4.809；再将各血清样本中目标蛋白的绝对含量代入该二元逻辑回归方程，即可得到各个血清样本的回归预测概率p，以可能的回归预测概率p作为诊断点，计算灵敏度和特异性，据此绘制ROC曲线(如图1所示)，AUC为0.9843，灵敏度为0.9412，特异性为0.9667。根据ROC曲线的坐标计算维登指数＝特异性+灵敏度-1，维登指数最大值时对应的预测概率p值为能进行诊断区分类风湿性关节炎缓解期VS活动期患者的最佳cut-off值0.511。
4、验证目标蛋白诊断类风湿性关节炎缓解期VS活动期患者的准确度
在验证集中，以HFREP1区分类风湿性关节炎缓解期VS活动期患者的最佳cut-off值为诊断阈值对类风湿性关节炎缓解期VS活动期患者的血清样本进行预测，以预测正确的样本数除以总样本数(26+16＝42)即为该目标蛋白区分类风湿性关节炎缓解期VS活动期患者的准确度。HFREP1诊断区分类风湿性关节炎缓解期VS活动期患者的准确度为97.62％。样本分布图如图2所示。
综上可见，血清蛋白HFREP1在诊断区分类风湿关节炎活动期和缓解期方面具有极高的诊断价值，诊断准确度高，比现有DAS28评分系统客观、易于操作，可以将血清蛋白HFREP1用于制备成诊断区分类风湿关节炎活动期和缓解期的诊断试剂盒。
实施例2：诊断区分类风湿关节炎活动期和缓解期的试剂盒
一种用于诊断区分类风湿关节炎活动期和缓解期的试剂盒，其中包括检测血清蛋白HFREP1含量的ELISA试剂。
上述实施例的作用在于具体介绍本发明的实质性内容，但本领域技术人员应当知道，不应将本发明的保护范围局限于该具体实施例。

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  1. 一种血清蛋白HFREP1在制备诊断类风湿性关节炎疾病状态的试剂或试剂盒中的应用，所述类风湿性关节炎疾病状态指活动期和缓解期。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109959787A (zh) * 2019-04-18 2019-07-02 漳州卫生职业学院 一种类风湿性关节炎辅助诊断试剂盒及检测方法
CN110283754A (zh) * 2019-07-11 2019-09-27 中国科学院北京基因组研究所 用于类风湿关节炎炎症状态评估及预后评价的肠道微生物菌群
CN110954702A (zh) * 2019-12-20 2020-04-03 江苏省中医院 一种血清蛋白hfrep1在类风湿性关节炎疾病状态诊断中的应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140051586A1 (en) * 2011-01-25 2014-02-20 Ignacio Pino High-throughput methods to produce, validate and characterize mmabs
CN102393456B (zh) * 2011-08-24 2014-02-12 北京正旦国际科技有限责任公司 一种用于检测hps的试剂盒
CN110029168B (zh) * 2019-05-09 2020-02-14 山东省立医院 基因fgl1在制备结直肠癌和肺癌诊断试剂盒的应用及试剂盒

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109959787A (zh) * 2019-04-18 2019-07-02 漳州卫生职业学院 一种类风湿性关节炎辅助诊断试剂盒及检测方法
CN110283754A (zh) * 2019-07-11 2019-09-27 中国科学院北京基因组研究所 用于类风湿关节炎炎症状态评估及预后评价的肠道微生物菌群
CN110954702A (zh) * 2019-12-20 2020-04-03 江苏省中医院 一种血清蛋白hfrep1在类风湿性关节炎疾病状态诊断中的应用

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
HOU, CHUNJIANG : "Electrophoresis of serum proteins of rheumatoid arthritis", CONTEMPORARY MEDICINE, vol. 14, no. 23, 5 December 2008 (2008-12-05), pages 55 - 56, XP009528628, ISSN: 1009-4393 *
PAN, XIAOFU ET AL.: "Identification of Diagnostic Biomarkers for Rheumatoid Arthritis by Proteomic Fingerprinting of Serum", IMMUNOLOGICAL JOURNAL, vol. 25, no. 5, 15 September 2009 (2009-09-15), pages 563 - 567,571, XP055822912, ISSN: 1000-8861 *
RAYBIOTECH, INC.: "Human HFREP1 ELISA", RAYBIOTECH, 19 December 2019 (2019-12-19), pages 1 - 3, XP055822905, Retrieved from the Internet <URL:https://www.raybiotech.com/human-hfrep1-elisa/> *
See also references of EP3929588A4
WU HUNG-TSUNG; OU HORNG-YIH; HUNG HAO-CHANG; SU YU-CHU; LU FENG-HWA; WU JIN-SHANG; YANG YI-CHING; WU CHAO-LIANG; CHANG CHIH-JEN: "A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes", DIABETOLOGIA, SPRINGER, vol. 59, no. 8, 25 May 2016 (2016-05-25), BERLIN, DE, pages 1732 - 1742, XP036243888, ISSN: 0012-186X, DOI: 10.1007/s00125-016-3991-7 *

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