Activated contact system and abnormal glycosaminoglycans in lupus and other auto- and non-autoimmune diseases

Peter Weiser, Yi Qian, Jing Pan, Xiaodong Zhou, Hong Lu, Daniel R. Studelska, Fei F. Shih, Lijuan Zhang

Research output: Chapter in Book/Report/Conference proceedingChapter

10 Scopus citations


Systemic lupus erythematosus (SLE), heparin-induced thrombocytopenia (HIT), rheumatoid arthritis (RA) are marked by the presence of autoantibodies against negatively changed DNA, phospholipids, heparin, and chondroitin sulfate, respectively. Heparin/protein complexes induce contact system activation in HIT patient plasmas. The activated contact system generates thrombin. Thrombin is responsible for thrombosis, a common cause of death and disabilities for both HIT and SLE. In this chapter, we analyze plasma contact system proteins, thrombin- and kallikrein-like activities, glucosamine and galactosamine content from SLE-, RA-, osteoarthritis (OA)-, and psoriasis (Ps)-patient plasmas in addition to pooled 30+ healthy patient plasmas. We found that all SLE patient plasmas exhibited abnormal contact systems marked by the absence of high molecular weight kininogen, the presence of processed C1 inhibitor (C1inh), the display of abnormal thrombin- and kallikrein-like activities, and increased levels of plasma glucosamine and galactosamine. Different patterns of contact system activation distinquish SLE, RA, and Ps whereas no contact system activation is observed in normal and OA patient plasmas. The presence of paradoxical "lupus anticoagulants" in certain thrombosis-prone SLE patient plasmas, marked by delayed clotting in clinical plasma test, was explained by the consumption of contact system proteins, especially high molecular weight kininogen. Finally, we discovered that mouse and human SLE autoantibodies bind to cell surface GAGs with structural selectivity. In conclusion, markers of abnormal contact system activation represent potential new targets for autoimmune disease diagnosis, prevention, and treatment. These markers might also be useful in monitoring SLE activity/severity and in pinpointing patients with SLE-associated arthritis and psoriasis.

Original languageEnglish (US)
Title of host publicationProgress in Molecular Biology and Translational Science
PublisherElsevier B.V.
Number of pages30
StatePublished - 2010

Publication series

NameProgress in Molecular Biology and Translational Science
ISSN (Print)1877-1173


  • C1 inhibitor
  • C3a
  • C5a
  • Contact system
  • Glycosaminoglycan
  • Kallikrein
  • Kininogen
  • Osteoarthritis
  • Psoriasis
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • thrombin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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