Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity

Rheumatol Int. 2016 Mar;36(3):359-64. doi: 10.1007/s00296-015-3372-4. Epub 2015 Oct 13.

Abstract

Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P < 0.001). The area under the ROC curve for progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P < 0.001). Interestingly, serum progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P < 0.001). The number of CD19(+)CD5(+)GrB(+) B cells was significantly higher in RA patients (P < 0.05); however, the level of Breg cells was not related to PGRN (P > 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

Keywords: Progranulin; Regulatory subsets of B cells; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD19 / blood
  • Area Under Curve
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes, Regulatory / immunology*
  • Biomarkers / blood
  • CD5 Antigens / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Granzymes / blood
  • Humans
  • Immunophenotyping / methods
  • Intercellular Signaling Peptides and Proteins / blood*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Progranulins
  • ROC Curve
  • Severity of Illness Index
  • Up-Regulation

Substances

  • Antigens, CD19
  • Biomarkers
  • CD5 Antigens
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • GZMB protein, human
  • Granzymes