liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Reduced anti-TNFα autoantibody levels coincide with flare in systemic lupus erythematosus
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
Department of Rheumatology, Lund University Hospital, Lund, Sweden.
Department of Rheumatology, Lund University Hospital, Lund, Sweden.
Show others and affiliations
2004 (English)In: Journal of Autoimmunity, ISSN 0896-8411, Vol. 22, no 4, 315-323 p.Article in journal (Refereed) Published
Abstract [en]

Deviating cytokine patterns, as a consequence of aberrant immunoregulation, is implicated to be of aetiopathogenetic importance in systemic lupus erythematosus (SLE). To evaluate the possibility of anti-cytokine autoantibody-mediated cytokine regulation/dysregulation, IgG class autoantibodies against cytokines (IL-1β, IL-6, IL-10, TNFα and TGFβ1) were analysed by enzyme-linked immunosorbent assay (ELISA) in serial serum samples from clinically well-characterized SLE patients and in normal human sera (NHS). Anti-TNFα autoantibody levels were lower in patients with active disease compared to inactive disease (P<0.001) as well as to NHS (P<0.001). The anti-TNFα antibody levels correlated inversely to the SLE disease activity index (SLEDAI) (r2=0.07, P<0.01), whereas anti-TGFβ antibodies were raised in SLE and correlated positively to levels of complement factor C1q (r2=0.08, P<0.005). Generally raised anti-cytokine antibody levels and correlations to disease activity measures were found in one individual. Inverse correlations were found comparing SLEDAI scores and autoantibodies to TNFα (r2=0.92) and IL-6 (r2=0.86) and positive correlations were found between levels of anti-TNFα and C1q (r2=0.86) and C3 (r2=0.90). We show, for the first time, a coincidence between reduced anti-TNFα autoantibody levels and disease exacerbation in SLE, which is of interest regarding aetiopathogenesis and disease control.

Place, publisher, year, edition, pages
2004. Vol. 22, no 4, 315-323 p.
Keyword [en]
Anti-cytokine antibodies, Disease activity, Immunoregulation, Systemic lupus erythematosus, SLEDAI, Tumour necrosis factor α
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13894DOI: 10.1016/j.jaut.2004.02.003OAI: oai:DiVA.org:liu-13894DiVA: diva2:22138
Available from: 2006-07-10 Created: 2006-07-10 Last updated: 2015-08-31
In thesis
1. C-reactive protein (CRP) and anti-CRP autoantibodies in systemic lupus erythematosus: a study on the occurrence and clinical implications of anti-CRP antibodies and CRP-mediated complement activation
Open this publication in new window or tab >>C-reactive protein (CRP) and anti-CRP autoantibodies in systemic lupus erythematosus: a study on the occurrence and clinical implications of anti-CRP antibodies and CRP-mediated complement activation
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of a wide range of autoantibodies, multiple organ involvement and by local formation or tissue deposition of immune complexes (ICs) in the inflamed organs. In contrast to most systemic inflammatory conditions, and despite raised levels of pro-inflammatory cytokines, SLE flares are rarely reflected by elevated C-reactive protein (CRP), an important acute-phase reactant in man with homologs in vertebrates and several invertebrates. As a part of the innate immune system, CRP binds certain molecules exposed on the surface of dying cells/apoptotic bodies and on the surface of pathogens and mediates their elimination by uptake in the reticuloendothelial system. CRP also interacts with IgG-containing immune complexes, binds Fc receptors and activates the complement system via C1q.

The aims of this thesis were to investigate the complement activation properties of CRP; to elucidate if anti-CRP antibodies occur in SLE and, if so, whether anti-CRP antibody levels correlate with disease activity in SLE; to test the hypothesis that autoantibodies to pro-inflammatory cytokines prevent rise of CRP; and to survey if autoantibodies to certain nuclear antigens or to CRP correlate with cytokine-inducing properties of ICs from SLE sera.

We have demonstrated that CRP bound to phosphorylcholine is a powerful activator of the classical complement pathway already in the CRP concentration range 4 to 10 mg/L, but with a marked inhibition at CRP levels above 150 mg/L. Autoantibodies to the monomeric form of CRP were found in approximately 40 percent of SLE patients and in a few sera from patients with primary Sjögren’s syndrome, but not in rheumatoid arthritis or in inflammatory bowel disease. The anti-CRP antibody levels showed significant correlations to several laboratory and clinical measurements, and anti-CRP positivity was associated with renal involvement in SLE. Native CRP levels were not correlated with anti-CRP or anti-cytokine antibody levels. Hence, the presence of antibodies to monomeric CRP or to CRP-inducing cytokines is an unlikely explanation to the relative failure of CRP response in patients with active lupus. However, antibodies to TNFα were found in subnormal levels at disease flares, whereas antibodies to TGFβ were found in supranormal levels as compared to healthy subjects. In contrast to antibodies against CRP and DNA, anti-SSA and anti-SSB antibodies may regulate the inflammatory process in SLE by enhancing IC formation and subsequent production of cytokines such as IL-6, IL-10 and IL-12p40. Hypothetically, anti-CRP autoantibodies may be of pathogenic importance, for instance by binding to monomeric CRP on cell and tissue surfaces and thereby increasing the risk of extrahepatic deposition of apoptotic material and in situ formation of ICs.

Place, publisher, year, edition, pages
Institutionen för molekylär och klinisk medicin, 2006
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 931
Keyword
autoantibodies, complement activation, C-reactive protein, cytokines, immune complex, immunoregulation, opsonization, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-7067 (URN)91-85497-66-5 (ISBN)
Public defence
2006-01-20, Eken, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Note
On the day of the defence data the status of article I was Submitted and the tile was "C-reactive protein activates or inhibits the classical complement pathway in a concentration dependent manner" and the status of article V was: Submitted.Available from: 2006-07-10 Created: 2006-07-10 Last updated: 2015-08-31

Open Access in DiVA

No full text

Other links

Publisher's full textLink to Ph.D. Thesis

Authority records BETA

Sjöwall, ChristofferErnerudh, JanSkogh, Thomas

Search in DiVA

By author/editor
Sjöwall, ChristofferErnerudh, JanSkogh, Thomas
By organisation
Rheumatology Faculty of Health SciencesDepartment of Rheumatology in ÖstergötlandClinical Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 131 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf