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Sökning: onr:"swepub:oai:DiVA.org:uu-3436" > Mechanisms of Inter...

Mechanisms of Interferon-α Induction in Systemic Lupus Erythematosus

Båve, Ullvi (författare)
Uppsala universitet,Institutionen för medicinska vetenskaper
Rönnblom, Lars (preses)
Alm, Gunnar V. (preses)
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Lundberg, Ingrid, Docent (opponent)
Institutionen för medicin, sektionen för reumatologi, Stockholm
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 (creator_code:org_t)
ISBN 915545643X
Uppsala : Acta Universitatis Upsaliensis, 2003
Engelska 70 s.
Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1267
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Patients with systemic lupus erythematosus (SLE) have an activated type I interferon (IFN) system with an ongoing IFN-α synthesis. This may be caused by circulating immune complexes, consisting of anti-DNA antibodies (Abs) and DNA, with IFN-α inducing capacity. Produced IFN-α may be crucial in the pathogenesis, because this cytokine can break tolerance and promote autoimmunity.In the present thesis, possible mechanisms of the IFN-α production in SLE were studied. To investigate whether IFN-α inducing material could be derived from apoptotic cells, IgG from SLE patients (SLE-IgG) were combined with apoptotic cells. This combination induced high IFN-α production in normal peripheral blood mononuclear cells (PBMC). The IFN-α induction was associated to presence of anti-RNP Abs, but not to anti-dsDNA Abs, indicating that two inducers could be active in SLE, one containing DNA and the other RNA.Apoptotic cells and SLE-IgG exclusively activated the natural interferon producing cells (NIPC) and the IFN-α response was enhanced by type I IFN and inhibited by IL-10 and TNF-α. The IFN-α induction was dependent on FcγRII, because blocking this receptor reduced IFN-α production and NIPC were found to express FcγRIIa.To further elucidate the role of different autoantibodies in the IFN-α induction, sera from patients with Sjögren´s syndrome (SS), containing autoantibodies to RNA binding proteins (SSA, SSB, RNP and/or Sm) were investigated. The combination of SS or SLE sera and apoptotic or necrotic cell material induced high IFN-α production in PBMC. RNA, but not DNA, was required for IFN-α induction, indicating that RNA and Abs to RNA-binding proteins form potent IFN-α inducing complexes.The findings in this thesis can explain central mechanisms for the activation of NIPC in SLE, and perhaps also other autoimmune diseases. This activation is mediated by interferogenic immune complexes, and modulating the NIPC activation may be a novel therapeutic approach in SLE.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

Medicine
Systemic lupus erythematosus
interferon inducer
apoptosis
autoantibodies
natural interferon-alpha producing cell
FcgammaRII
Sjögren´s syndrome
Medicin
Dermatology and venerology,clinical genetics, internal medicine
Dermatologi och venerologi, klinisk genetik, invärtesmedicin
Medicine
medicin

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