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Cystatin C binds serum amyloid A, downregulating its cytokine-generating properties

In English

Författare

Summary, in English

Objective. To assess the interaction between cystatin C (CysC) and serum amyloid A protein (SAA). Methods. Levels of CysC and SAA and antibodies against these proteins were assessed in the paired blood and synovial fluid (SF) samples of 90 patients with rheumatoid arthritis (RA). Age and sex matched individuals having normal iohexol clearance (n = 90) and SF following joint trauma (n = 40) were used as controls. In vitro experiments included assessment of interaction between CysC and SAA by ELISA and the influence of CysC on SAA functions. Results. A pilot screening for cystatins C, E, and F in blood and SF of patients with RA found CysC to be by far the predominant extracellular cystatin. Circulating CysC levels were significantly lower in patients with RA compared to the matched controls (0.81 +/- 0.03 vs 1.01 +/- 0.03 mg/l; p = 0.05). These low CysC levels could not be explained by the presence of anti-CysC antibodies in patients with RA. In contrast, concentrations of CysC that accumulated in the inflamed SF were significantly greater in patients with erosive RA (1.66 +/- 0.08 mg/l) compared to nonerosive RA (1.36 +/- 0.06 mg/l; p = 0.003) and controls (1.18 +/- 0.03 mg/l; p = 0.043). In vitro studies showed direct binding of CysC to SAA. CysC/SAA binding impaired proinflammatory effects of SAA, reducing its ability to trigger expression of proinflammatory cytokines. Conclusion. Our study shows a relative deficiency of circulating CysC during systemic inflammation in RA. Physical interaction between CysC and the acute-phase protein SAA (1) provides an explanation for CysC deficiency; and (2) suggests that CysC is regulating inflammatory responses. We hypothesize that decreased systemic CysC levels predispose to accelerated atherosclerosis and development of amyloidosis in patients with RA.

Publiceringsår

2007

Språk

Engelska

Sidor

1293-1301

Publikation/Tidskrift/Serie

Journal of Rheumatology

Volym

34

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

Journal of Rheumatology Publishing Company Limited

Ämne

  • Rheumatology and Autoimmunity

Nyckelord

  • cytokines
  • cystatin C
  • serum amyloid A
  • rheumatoid arthritis

Status

Published

Forskningsgrupp

  • Joint and Soft Tissue Unit

ISBN/ISSN/Övrigt

  • ISSN: 0315-162X