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Serum progranulin levels in Hispanic rheumatoid arthritis patients treated with TNF antagonists: a prospective, observational study

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Abstract

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.

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Acknowledgments

The authors thank the subjects of this study for their participation.

This work was supported in part by an ASPIRE Award in Rheumatology Research to William Stohl from Pfizer and by National Institutes of Health grants R01 AR062207 and R01 AR061484 to Chuanju Liu.

Authors’ contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.

Study conception and design: KY, CL, WS.

Acquisition of data: JJ, KY, RR, RN, QT, JJ, NF.

Analysis and interpretation of data: NF, CL, WS.

Author information

Authors and Affiliations

  1. 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 Johnson, Karen Yeter, Rosy Rajbhandary, Rebekah Neal & William Stohl

  2. Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA

    Qingyun Tian, Jinlong Jian & Chuanju Liu

  3. José Carreras Center for Immuno- and Gene Therapy, Internal Medicine I, Saarland University Medical School, Homburg, Saar, Germany

    Natalie Fadle & Lorenz Thurner

Authors
  1. Jennifer Johnson
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  2. Karen Yeter
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  3. Rosy Rajbhandary
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  4. Rebekah Neal
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  5. Qingyun Tian
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  6. Jinlong Jian
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  7. Natalie Fadle
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  8. Lorenz Thurner
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  9. Chuanju Liu
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  10. William Stohl
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Corresponding author

Correspondence to William Stohl.

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Ethical standards

The protocol was reviewed and approved by the LAC + USC Institutional Review Board (Protocol HS-12-00394). Written informed consent was obtained from all subjects prior to enrollment.

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Supplemental Figure 1

Baseline distribution of serum PGRN levels. Each circle represents an individual RA patient. Open circles denote “PGRN-low”, and closed circles denote “PGRN-high”. (GIF 103 kb)

High resolution image (TIFF 64 kb)

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Johnson, J., Yeter, K., Rajbhandary, R. et al. Serum progranulin levels in Hispanic rheumatoid arthritis patients treated with TNF antagonists: a prospective, observational study. Clin Rheumatol 36, 507–516 (2017). https://doi.org/10.1007/s10067-016-3467-7

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  • DOI: https://doi.org/10.1007/s10067-016-3467-7

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