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The Role of Fc Gamma Receptors in Experimental Arthritis
Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
2004 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Induction of collagen-induced arthritis (CIA), an animal model for human rheumatoid arthritis, is dependent on anti-collagen type II (CII) antibodies. The effector mechanism by which autoantibodies contribute to inflammatory reactions in autoimmune diseases is not well understood. In this thesis I have studied the effector pathways used by IgG anti-CII antibodies to initiate arthritis, namely the IgG Fc receptors (FcγRs) and the complement system. We have found that FcγRIII is crucial for development of CIA, as CII-immunized mice lacking this receptor do not develop arthritis and IgG1 and IgG2b anti-CII antibodies require FcγRIII to trigger arthritis when transferred to naïve mice. The antibody-mediated arthritis was further enhanced in mice deficient in the inhibitory FcγRIIB, indicating that FcγRIIB regulates the activation of FcγRIII. Furthermore, we demonstrate that FcγRIII exist as three distinct haplotypes in mice, FcγRIII:H, FcγRIII:V and FcγRIII:T. Mice expressing the FcγRIII:H haplotype are more susceptible to CIA than mice expressing the FcγRIII:V haplotype, indicating that certain FcγRIII haplotype predisposes for CIA. We also show that the most likely FcγRIII-expressing effector cell in CIA is the macrophage, since FcγRIII-expressing macrophages exclusively can induce arthritis in FcγRIII-deficient mice challenged for CIA.

The complement system was also investigated in development of CIA. We found that this effector pathway is also necessary for onset of arthritis, as CIA was inhibited by treatment with anti-complement factor 5 (C5) antibodies. C5-deficient mice could neither develop CIA unless provided with C5-containing sera.

Taken together, the work presented in this thesis indicates that FcγRs and the complement system are crucial for the induction of experimental arthritis. These findings are important for understanding the mechanisms behind rheumatoid arthritis and blocking of these effector pathways may in the future be used as treatment of rheumatoid arthritis.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis , 2004. , s. 56
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1397
Nyckelord [en]
Immunology, Rheumatoid arthritis, Antibodies, Fc receptors, Complement, Transgenic/Knockout mice
Nyckelord [sv]
Immunologi
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:uu:diva-4724ISBN: 91-554-6123-9 (tryckt)OAI: oai:DiVA.org:uu-4724DiVA, id: diva2:165585
Disputation
2005-02-04, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, Uppsala, 09:15
Opponent
Handledare
Tillgänglig från: 2005-01-14 Skapad: 2005-01-14 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Delarbeten
1. Expression of FcγRIII is required for development of collagen-induced arthritis
Öppna denna publikation i ny flik eller fönster >>Expression of FcγRIII is required for development of collagen-induced arthritis
Visa övriga...
2002 Ingår i: European Journal of Immunology, Vol. 32, s. 2915-2922Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-92480 (URN)
Tillgänglig från: 2005-01-14 Skapad: 2005-01-14Bibliografiskt granskad
2. FcγRIII-expressing macrophages are essential for the development of collagen-induced arthritis
Öppna denna publikation i ny flik eller fönster >>FcγRIII-expressing macrophages are essential for the development of collagen-induced arthritis
Manuskript (Övrigt vetenskapligt)
Identifikatorer
urn:nbn:se:uu:diva-92481 (URN)
Tillgänglig från: 2005-01-14 Skapad: 2005-01-14 Senast uppdaterad: 2010-01-13Bibliografiskt granskad
3. Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
Öppna denna publikation i ny flik eller fönster >>Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
Visa övriga...
2003 Ingår i: European Journal of Immunology, Vol. 33, s. 2269-2277Artikel i tidskrift (Refereegranskat) Published
Identifikatorer
urn:nbn:se:uu:diva-92482 (URN)
Tillgänglig från: 2005-01-14 Skapad: 2005-01-14Bibliografiskt granskad
4. IgG Fc receptor polymorphisms and C5 influence susceptibility to collagen-induced arthritis
Öppna denna publikation i ny flik eller fönster >>IgG Fc receptor polymorphisms and C5 influence susceptibility to collagen-induced arthritis
Artikel i tidskrift (Refereegranskat) Submitted
Identifikatorer
urn:nbn:se:uu:diva-92483 (URN)
Tillgänglig från: 2005-01-14 Skapad: 2005-01-14Bibliografiskt granskad

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