Activation of Complement by Pigment Epithelium-Derived Factor in Rheumatoid Arthritis

Publikation: Forskning - peer reviewTidsskriftartikel

DOI

  • Leonie M. Vogt
    Leonie M. VogtDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Skåne County Council, S-20502 Malmö, Sweden.
  • Simone Talens
    Simone TalensDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Skåne County Council, S-20502 Malmö, Sweden.
  • Ewa Kwasniewicz
    Ewa KwasniewiczDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Skåne County Council, S-20502 Malmö, Sweden.
  • Carsten Scavenius
  • André Struglics
    André StruglicsSection of Orthopaedics, Department of Clinical Sciences Lund, Lund University, SE-21184 Lund, Sweden; and.
  • Jan J Enghild
  • Tore Saxne
    Tore SaxneSection of Rheumatology, Department of Clinical Sciences Lund, Lund University, S-22185 Lund, Sweden.
  • Anna M Blom
    Anna M BlomDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Skåne County Council, S-20502 Malmö, Sweden; Anna.Blom@med.lu.se.

The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.

OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind199
Sider (fra-til)1113-1121
Antal sider9
ISSN0022-1767
DOI
StatusUdgivet - 1 aug. 2017

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