Serum progranulin levels in Hispanic rheumatoid arthritis patients treated with TNF antagonists: a prospective, observational study.
Since progranulin (PGRN) is a natural ligand of TNF receptors, we assessed whether serum PGRN levels predict and/or reflect responsiveness of RA patients to TNF-antagonist therapy. TNF-antagonist-naïve RA patients (N = 35) were started on TNF-antagonist therapy. At baseline and at follow-up visits, DAS28-ESR, DAS28-CRP, and CDAI were calculated, and venous blood was collected for serum PGRN determination. Disease activity and clinical response were based on EULAR criteria. Baseline serum PGRN levels varied considerably and correlated with ESR and CRP. DAS28-ESR, DAS28-CRP, and CDAI were greater in "PGRN-high" than in "PGRN-low". Baseline serum PGRN levels did not predict clinical responsiveness to TNF-antagonist therapy. Nevertheless, changes in serum PGRN levels at 274+ days following initiation of TNF-antagonist therapy correlated with changes in ESR, CRP, DAS28-ESR, DAS28-CRP, and CDAI. At this time, DAS28-ESR, DAS28-CRP, and CDAI in PGRN-high and PGRN-low equalized, but serum PGRN levels remained greater in PGRN-high than in PGRN-low. To our knowledge, the present report is the first prospective study to longitudinally assess changes in serum PGRN levels following initiation of TNF-antagonist therapy. Although pre-treatment serum PGRN levels may not predict clinical responsiveness to TNF-antagonist therapy, changes in serum PGRN levels correlate with changes in disease metrics over time. By inference, administration of PGRN may represent an effective therapeutic option for development in RA patients.
Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, 2011 Zonal Ave. HMR 711, Los Angeles, CA, 90033, USA.
Jennifer
J
Johnson
Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, 2011 Zonal Ave. HMR 711, Los Angeles, CA, 90033, USA.
Karen
K
Yeter
Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, 2011 Zonal Ave. HMR 711, Los Angeles, CA, 90033, USA.
Rosy
R
Rajbhandary
Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, 2011 Zonal Ave. HMR 711, Los Angeles, CA, 90033, USA.
Rebekah
R
Neal
Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.
Qingyun
Q
Tian
Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.
Jinlong
J
Jian
José Carreras Center for Immuno- and Gene Therapy, Internal Medicine I, Saarland University Medical School, Homburg, Saar, Germany.
Natalie
N
Fadle
José Carreras Center for Immuno- and Gene Therapy, Internal Medicine I, Saarland University Medical School, Homburg, Saar, Germany.
Lorenz
L
Thurner
Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.
Chuanju
C
Liu
Division of Rheumatology, Department of Medicine, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, 2011 Zonal Ave. HMR 711, Los Angeles, CA, 90033, USA. stohl@usc.edu.
William
W
Stohl
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D000077153:Progranulins; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D018501:Antirheumatic Agents; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone; D008727:Methotrexate
Progranulin; Prospective observational study; Rheumatoid arthritis; TNF-antagonist therapy