Development and clinical validation of a multiplexed massspectrometry- based assay to improve diagnosis of Rheumatoid Arthritis (ARTHRITIS)

Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF)
are essential serological biomarkers for diagnosis of rheumatoid arthritis
(RA). However, the limitation of these markers for RA diagnosis is that
they are absent in about one third of RA patients, a percentage which is
even higher in early RA. It is now widely accepted that identification of
RA in its earliest stages significantly improves a patient’s prognosis.
Though much research has been performed in an attempt to close this
serological gap, novel approaches are warranted to identify new
biomarkers to improve diagnosis for RA. Though seen as an expensive
and complex device for assay development, mass spectrometry (MS)
has become a powerful tool in medical diagnostics, providing highly
specific molecular information in real-time for clinical analysis. Only
recently, a novel MS platform has been developed in the lab of Clinical
and Diagnostic Immunology and PharmAbs in which differences in
amino acid sequences of the hypervariable complementaritydetermining
regions (CDRs) of antibody molecules between patients and
controls can be detected, without a required prior knowledge of the
antigen. Rather than being restricted to measuring autoantibodies to
one or more targets, this approach allows to work hypothesis-free. With
this MS-based CDR peptide discovery platform, we were able to identify
RA-specific unique CDR peptides that are potential biomarkers for
diagnosis of RA patients who are negative for ACPA and RF. This project
thus aims to design an innovative MS-based assays with RA-unique CDR
peptides to improve and facilitate the clinical management of RA
patients.