umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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
Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Reumatology.
Show others and affiliations
2003 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 12, no 10, 766-774 p.Article in journal (Refereed) Published
Abstract [en]

The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI &GE; 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls ( P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1β MCP-1, SDF-1α, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/ serum.

Place, publisher, year, edition, pages
2003. Vol. 12, no 10, 766-774 p.
Keyword [en]
chemokines; chemokine receptors; SLE; T-lymphocytes
National Category
Immunology in the medical area Rheumatology and Autoimmunity
Research subject
Clinical Immunology; Medicine, rheumatology
Identifiers
URN: urn:nbn:se:umu:diva-39152DOI: 10.1191/0961203303lu467oaOAI: oai:DiVA.org:umu-39152DiVA: diva2:388933
Available from: 2011-01-18 Created: 2011-01-18 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Immunological mechanisms in systemic autoimmunity: autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis
Open this publication in new window or tab >>Immunological mechanisms in systemic autoimmunity: autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration.

Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE.

Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR.

Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody.

In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders.

Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2011. 68 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1401
Keyword
autoimmunity, chemokines, T-cells, autoantibodies, CD91
National Category
Immunology in the medical area Rheumatology and Autoimmunity
Research subject
Clinical Immunology; Medicine, rheumatology
Identifiers
urn:nbn:se:umu:diva-42954 (URN)978-91-7459-143-9 (ISBN)
Public defence
2011-05-12, Betula, Norrlands universitetssjukhus, by 6M, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-04-20 Created: 2011-04-15 Last updated: 2011-04-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Eriksson, CatharinaEneslätt, KjellIvanoff, JRantapää-Dahlqvist, SolbrittSundqvist, Karl-Gösta
By organisation
Clinical ImmunologyReumatology
In the same journal
Lupus
Immunology in the medical areaRheumatology and Autoimmunity

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 115 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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