Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project

Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80–90%.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants FIS PI21/01545, PI19/01206, PI20/00793, CB16/12/00400, and CB06/01/0040. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Units belong to ProteoRed, PRB3-ISCIII, supported by grants PT17/0019/0023 and PT17/0019/0014 of the PE I+D+I 2017-2020, funded by ISCIII and FEDER. This research work was funded by the European Commission – NextGeneration EU, through CSIC’s Global Health Platform (PTI+ Salud Global). This work was performed in the framework of NanoMedicine CSIC HUB (ref 202180E048). P.J.-V. is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYL-EDU/601/2020. A.L.-V. is supported by VIII Centenario-USAL PhD Program. L.L. is supported by a Sara Borrell contract (CD19/00229)