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Balance between sur...
Balance between survivin, a key member of the apoptosis inhibitor family, and its specific antibodies determines erosivity in rheumatoid arthritis
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- Bokarewa, Maria, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
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- Silfverswärd Lindblad, Sofia, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
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- Bokarew, Demitri, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine
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- Tarkowski, Andrej, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
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(creator_code:org_t)
- 2005
- 2005
- English.
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In: Arthritis Res Ther. - 1478-6362. ; 7:2
- Related links:
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Abstract
Subject headings
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- Rheumatoid arthritis (RA) is a highly heterogeneous disease with respect to its joint destructivity. The reasons underlying this heterogeneity are unknown. Deficient apoptosis in rheumatoid synovial tissue has been recently demonstrated. We have therefore decided to study the synovial expression of survivin, a key member of the apoptosis inhibitor family. The levels of survivin and antibodies against survivin were assessed by an ELISA in matched blood and synovial fluid samples collected from 131 RA patients. Results were related to joint erosivity at the time of sampling. Monocytes were transfected with survivin anti-sense oligonucleotides and were assessed for their ability to produce inflammatory cytokines. Survivin levels were significantly higher in patients with destructive disease as compared with in RA patients displaying a non-erosive disease. High survivin levels were an independent prognostic parameter for erosive RA. In contrast, high levels of antibodies against survivin were found in patients with non-erosive RA, and were negatively related to erosivity. Survivin levels in RA patients were influenced by treatment, being significantly lower among patients treated with disease-modifying anti-rheumatic drugs. Specific suppression of survivin mRNA resulted in downregulation of IL-6 production. We conclude that survivin determines the erosive course of RA, whereas survivin antibodies lead to a less aggressive course of the disease. These findings together with decreased survivin levels upon disease-modifying anti-rheumatic drug treatment, and the downregulation of inflammatory response using survivin anti-sense oligonucleotides, suggest that extracellular survivin expression mediates the erosive course of joint disease whereas autoimmune responses to the same molecule, manifested as survivin targeting antibodies, mediate protection.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Adolescent
- Adult
- Aged
- Aged
- 80 and over
- Antirheumatic Agents/therapeutic use
- Apoptosis
- Arthritis
- Rheumatoid/blood/drug therapy/*immunology/pathology
- Autoantibodies/biosynthesis/*immunology
- Autoantigens/genetics/*immunology/metabolism
- Autoimmune Diseases/blood/drug therapy/*immunology/pathology
- Cells
- Cultured/metabolism
- Cytokines/biosynthesis
- Disease Progression
- Extracellular Fluid/metabolism
- Female
- Humans
- Immunoglobulin G/biosynthesis/immunology
- Immunoglobulin M/biosynthesis/immunology
- Interleukin-6/secretion
- Joints/*pathology
- Male
- Microtubule-Associated Proteins/genetics/*immunology/metabolism
- Middle Aged
- Monocytes/metabolism/secretion
- Neoplasm Proteins/genetics/*immunology/metabolism
- Oligodeoxyribonucleotides
- Antisense/genetics
- Predictive Value of Tests
- Prognosis
- Synovial Fluid/*metabolism
- Thionucleotides/genetics
- Transcription
- Genetic
- Transfection
Publication and Content Type
- ref (subject category)
- art (subject category)
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