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OP0313 P75 low affinity receptor of nerve growth factor on peripheral leukocytes and cd11c-positive dendritic cells are upregulated in patients with systemic lupus erythematosus
  1. S Welle,
  2. AM Wolf,
  3. MF Seidel
  1. Medizinische Klinik III, Hematology, Oncology and Rheumatology, University Hospital of Bonn, Bonn, Germany

Abstract

Background The nervous system regulates rheumatic diseases in neurogenic inflammation (NI). Nerve growth factor (NGF) plays a pivotal role in NI and chronic nociceptive pain of degenerative musculoskeletal diseases [1]. Clinical trials using NGF antagonists have shown impressive analgesic efficacy in these disorders [2]. However, the role of NGF in autoimmune inflammatory diseases is not completely understood although NI perhaps induces and/or mediates disease activity. NGF-receptor expression on peripheral lymphocytes may reflect NI activity.

Objectives The aim of this study was to identify the expression levels of the NGF receptor with high affinity (TrkA) and low affinity (p75) on leukocyte subsets of SLE patients, as compared to healthy controls (HC).

Methods The number of TrkA- and p75-positive cells was quantified in 13 SLE patients (diagnosed according to the 1997 ACR revised criteria). CD4, CD8, CD11b, CD11c, CD14, CD16, CD19, CD56 and CD66b antibodies, and isotype controls were used. Cells were quantified by multicolour flow cytometry and compared to gender and age-matched HC (n=13) using the Mann-Whitney-U-Test. Values <0.05 were considered statistically significant. Patients were further subgrouped for high or low disease activity as determined by SLEDAI, ANA, anti-dsDNA, CRP, complement C3/C4 and ESR, and compared to HC using the Kruskal-Wallis test and Mann-Whitney-U-test. NGF serum concentrations were determined by ELISA.

Results In SLE, TrkA expression on peripheral leukocytes (%±SD) was not different from HC and was highest on CD14+ cells (15.5±20.6). In contrast, p75 was significantly increased on CD16+ (2.4±3.0 vs. 0.9±0.6, p=0.044) and CD56+ leukocytes (1.5±1.7 vs. 0.4±0.3, p=0.022) in SLE vs. HC. Further subgroup analyses showed that TrkA (0.6±0.3 vs. 1.8±1.3, p=0.035) and p75 (0.4±0.3 vs. 2.3±1.8, p=0.014) were decreased on CD56+ cells in patients with high SLEDAI vs. patients with low SLEDAI scores. Similarly, a reduction of p75 on CD19+ B cells was associated with high SLEDAI (0.8±0.7 vs. 10.8±16.5, p=0.018) whereas p75 expression was significantly higher on CD56+ cells in SLE with low SLEDAI as compared to HC (2.3±1.8 vs. 0.2±0.2, p=0.007). CD11c+ dendritic cells (DC) did not show differential expression for TrkA or p75, however, they were increased in SLE as compared to HC (5.4±2.5 vs. 2.5±0.6, p=0.0001). Interestingly, DC were also significantly elevated in SLE with high SLEDAI, anti-dsDNA, ANA and ESR. NGF serum concentrations did not differ between SLE and HC.

Conclusions Our data for the first time demonstrate differential NGF receptor expression on an extensive panel of peripheral blood leukocytes in SLE and HC. p75 appears to be the major differentially regulated receptor for NGF. The decrease of TrkA and p75 on CD56+ and p75 on CD19+ cells in patients with high SLEDAI activity is unclear and may reflect a negative feedback mechanism. The increased CD11c+ DC might indicate additional inflammatory activation in SLE. Further studies are needed to analyse these findings.

References

  1. Seidel MF, Herguijuela M, Forkert R, Otten U. Nerve growth factor in rheumatic diseases. Sem. Arthr. Rheum. 2010; 40(2):109–26.

  2. Seidel MF, Wise BL, Lane NE. Nerve growth factor: an update on the science and therapy. Osteoarthritis Cartilage 2013; 21(9):1223–8.

References

Disclosure of Interest None declared

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