Browsing by Author "Martinez-Taboada, Victor"
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Item Anti-Protein-Arginine Deiminase 4 IgG and IgA Delineate Severe Rheumatoid Arthritis.(Diagnostics, 2022) Martínez Prat, Laura; Martinez-Taboada, Victor; Santos Tejedor, Cruz; Lopez-Hoyos, Marcos; Mahler, MichaelThere is a strong need for biomarkers of rheumatoid arthritis (RA) in all phases of the patient’s journey and to enable the implementation of precision medicine strategies to improve patient care. The objective of this study was to evaluate the presence of anti-protein-arginine deiminase (PAD) 4 IgG and IgA in the sera of RA patients and disease controls, and to investigate their association with joint erosion and biological treatment use. Sera from 104 RA and 155 controls were tested for the presence of anti-PAD4 IgG and IgA using a new particle-based multi-analyte technology (PMAT). Information on the erosive disease and biological treatment use was available for 54 of the RA patients, who were also tested for anti-citrullinated protein antibodies (ACPA). An association between the autoantibodies and these clinical features was investigated. Anti-PAD4 showed sensitivity and specificity values of 25.0% and 94.2% for IgG and of 21.2% and 94.8% for IgA for RA, respectively. The levels of these antibodies were also significantly higher in RA patients vs. controls, in erosive RA vs. non-erosive disease, and in patients under biologics vs. patients that were not on this treatment regimen. The anti-PAD4 IgG and IgA levels were correlated (rho = 0.60, p < 0.0001), but individuals that were positive for only one of the two isotypes were also observed. Anti-PAD4 IgG and IgA are associated with severe RA, and they represent valuable biomarkers for prognosis prediction and patient stratification.Item Association of anti-pad4 antibodies with erosion and biological treatment use in rheumatoid arthritis.(https://ard.bmj.com/content/78/Suppl_2/315.1, 2019) Martínez Prat, Laura; Martinez-Taboada, Victor; Lopez-Hoyos, Marcos; Mahler, MichaelBackground: Novel biomarkers have been described in rheumatoid arthritis (RA) patients, including antibodies to carbamylated proteins (anti-CarP) and to protein-arginine deiminases (PAD). Anti-PAD4 antibodies are associated with anti-citrullinated protein antibodies (ACPA) and worse baseline radiographic joint damage [1]. A subset of anti-PAD4 antibodies that cross-react with PAD3 and are associated with erosive disease, ACPA and progress despite treatment have also been described [1]. Objectives: To evaluate several novel RA markers in a cohort of RA and controls and their association with erosive disease and biological treatment use in RA. Methods: Sera from 116 RA patients [63 young onset RA (YORA) and 53 elderly onset RA (EORA)] and 155 controls [134 polymyalgia rheumatica (PMR) patients and 21 healthy individuals (HI) older than 60 years old] were included. Information on erosion status and biological treatment was available for 56 of the RA patients. The samples were tested for anti-PAD3 and anti-PAD4 IgG using the novel particle-based multi-analyte technology (PMAT, research use only, RUO), as well as for ACPA [CCP3 IgG ELISA and chemiluminescent immunoassay (CIA)] and anti-CarP IgG (ELISA, RUO). Results: Significantly higher levels of anti-PAD3, anti-PAD4 and ACPA (ELISA and CIA) but not CarP were observed in YORA vs. EORA (p<0.0001 for anti-PAD3 and ACPA ELISA and CIA, p=0.0016 for anti-PAD4). In the RA patients with erosion and treatment information available, anti-PAD4 antibody levels, but not ACPA, anti-CarP or anti-PAD3, were significantly higher in patients on biologic treatment vs. patients that were not on biologics (p=0.0017). Anti-PAD4 positive patients, were 10.1 [95% CI 2.5-52.0, p=0.0002] times more likely to be on biologic treatment vs. the negative group. Similarly, anti-PAD4 antibodies, but neither ACPA nor anti-CarP or anti-PAD3, were also significantly higher in patients with joint erosions (p=0.0354). All patients that were positive for anti-PAD4 antibodies (n=21) had erosive disease. Anti-PAD4 positive patients, were 20.2 [95% CI 1.1-363.2, p=0.0041] times more likely to have erosive disease.