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%.