Background/Purpose: Psoriatic arthritis (PsA) can be challenging to diagnose due to the lack of specific biomarkers. Although a few teams have demonstrated the presence of autoantibodies (autoAB) in PsA, none have been confirmed and no large-scale screening has ever been carried out.
Our objective was to conduct a comprehensive screening of antibody responses in PsA using Human Protein ProtoArray® (Invitrogen®) and subsequently identify specifically recognized B epitopes through peptide arrays commercialized by JPT®.

Methods: One hundred and sixty participants were included: 84 PsA patients and 76 controls (27 Rheumatoïd Arthritis [RA], 22 Systemic Lupus Erythematosus [SLE] and 27 healthy controls [HC]).

Screening of PsA-specific AB responses was conducted using Human Protein ProtoArray® from Life Technologies©. Patient serum, diluted at 1/500, was exposed to 9483 well-characterized human proteins expressed through a baculovirus expression system. AB presence was detected by adding fluorochrome-conjugated anti-human IgG.

B cell epitopes were analyzed using JPT® peptide arrays. Peptide sequences of 15 amino acids (aa) from LURM-A, synthesized on the array with a 3-aa overlap, were exposed to patient serum diluted at 1/200. AB responses for each peptide were analyzed using a fluorescence scanner after adding fluorochrome-conjugated anti-IgG.

Statistical tests, including χ2, Wilcoxon-Mann-Whitney, and ROC analysis, were performed. All patients provided informed consent for sample collection (Ethics No: DC-2008-327; convention INSERM2023-015/RCAPHM23_0069) and were pseudonymized.

Results: Protein microarray analysis identified a protein named LURM-A* (patent pending) specifically recognized by the PsA population. ROC analysis confirmed excellent diagnostic performance with an AUC of 0.785, p < 0.0001, sensitivity (Se) of 73.2%, and specificity (Spe) of 83.0%.

Peptide array containing 15aa LURM-A peptides identified two overlapping peptides – named A55 and A56 – with interesting diagnostic performance in distinguishing PsA from the overall control population. For A-55, AUC was 0.576, p: 0.0082*, with Se 47.6% and Spe 73.9%, and for A-56, AUC was 0.670, p: 0.0001*, with Se 72.6% and Spe 50.7%.

Conclusion: PsA patients exhibit a specific AB response against LURM-A peptides A55 and A56 on JPT® peptide arrays. Further exploration of the pathophysiological relevance of this protein requires functional studies. An alternative technique (specific ELISA) is underway to confirm this specificity and explore the diagnostic utility of these peptides.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/exploring-antibodies-in-psoriatic-arthritis-a-novel-autoimmune-biomarker-discovered/