Andrea Seaman1, Erika Darrah2, Maria Infantino3, Francesca Meacci4, Mariangela Manfredi3, Maurizio Benucci4, Michael Mahler5. 1. Inova Diagnostics, Inc., San Diego, CA, USA. 2. Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Immunology and Allergology Laboratory Unit, Ospedale S. Giovanni di Dio, Florence, Italy. 4. Rheumatology Unit, Ospedale S. Giovanni di Dio, Florence, Italy. 5. Inova Diagnostics, Inc., San Diego, CA, USA. Electronic address: mmahler@inovadx.com.
Abstract
BACKGROUND: Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage. METHODS: To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA. RESULTS: Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES. CONCLUSION: In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients.
BACKGROUND: Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage. METHODS: To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RApatients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA. RESULTS: Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES. CONCLUSION: In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RApatients.
Authors: Iris Navarro-Millán; Erika Darrah; Andrew O Westfall; Ted R Mikuls; Richard J Reynolds; Maria I Danila; Jeffrey R Curtis; Antony Rosen; S Louis Bridges Journal: Arthritis Res Ther Date: 2016-10-22 Impact factor: 5.156
Authors: Erika Darrah; Jon T Giles; Ryan L Davis; Pooja Naik; Hong Wang; Maximilian F Konig; Laura C Cappelli; Clifton O Bingham; Sonye K Danoff; Felipe Andrade Journal: Front Immunol Date: 2018-11-20 Impact factor: 7.561