Investigation of Newly Diagnosed Drug-Naive Patients with Systemic Autoimmune Diseases Revealed the Cleaved Peptide Tyrosine Tyrosine (PYY 3-36) as a Specific Plasma Biomarker of Rheumatoid Arthritis

• Published in: Mediators of inflammation Vol. 2021; pp. 5523582 - 9
• Main Authors: Balog, Jozsef A., Kemeny, Agnes, Puskas, Laszlo G., Burcsar, Szilard, Balog, Attila, Szebeni, Gabor J.
• Format: Journal Article
• Language: English
• Published: United States Hindawi 2021; Hindawi Limited
• Subjects: Age; Aged; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Autoimmune diseases; Autoimmune Diseases - drug therapy; Autoimmune Diseases - physiopathology; Biomarkers; Biomarkers - blood; Confidence intervals; Cytokines; Cytokines - metabolism; Disease; Female; Gender; Humans; Interleukin 10; Interleukin 12; Interleukin 13; Interleukin 4; Laboratories; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Machine Learning; Macrophage colony-stimulating factor; Male; Middle Aged; Nonsteroidal anti-inflammatory drugs; Patients; Pattern Recognition, Automated; Plasma; Plasma proteins; Prognosis; Proteins; Rheumatoid arthritis; Scleroderma; Scleroderma, Systemic - blood; Scleroderma, Systemic - immunology; Software; Standard deviation; Systemic lupus erythematosus; Systemic sclerosis; Tyrosine; Tyrosine - chemistry; γ-Interferon
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2021/5523582

There is a current imperative to reveal more precisely the molecular pathways of early onset of systemic autoimmune diseases (SADs). The investigation of newly diagnosed drug-naive SAD patients might contribute to identify novel disease-specific and prognostic markers. The multiplex analysis of 30 plasma proteins in 60 newly diagnosed drug-naive SADs, such as RA (rheumatoid arthritis, n=31), SLE (systemic lupus erythematosus, n=19), and SSc (systemic scleroderma, n=10) patients, versus healthy controls (HCs, n=40) was addressed. Thirty plasma cytokines were quantified using the Procarta Plex™ panel. The higher expression of IL-12p40, IL-10, IL-13, IFN-γ, M-CSF, IL-4, NTproBNP, IL-17A, BMP-9, PYY (3-36), GITRL, MMP-12, and TNFRSF6 was associated with RA; IL-12p40, M-CSF, IL-4, GITRL, and NTproBNP were higher in SLE; or NTproBNP, PYY (3-36), and MMP-12 were increased in SSc over HCs, respectively. The cleaved peptide tyrosine tyrosine (PYY 3-36) was elevated in RA (361.6±47.7 pg/ml) vs. HCs (163.96±14.5 pg/ml, mean±SEM, ∗∗∗p=4×10−5). The CI (95%) was 268.05-455.16 pg/ml for RA vs. 135.55-192.37 pg/ml for HCs. The elevated PYY (3-36) level correlated significantly with the increased IL-4 or GITRL concentration but not with the clinical scores (DAS28, CRP, ESR, RF, aMCV). We are the first to report cleaved PYY (3-36) as a specific plasma marker of therapy-naive RA. Additionally, the multiplex plasma protein analysis supported a disease-specific cytokine pattern in RA, SLE, and SSc, respectively.