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- Green, P G, et al.
(författare)
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Role of adrenal medulla in development of sexual dimorphism in inflammation
- 2001
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Ingår i: European Journal of Neuroscience. - 0953-816X .- 1460-9568. ; 14, s. 1436-1444
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Tidskriftsartikel (refereegranskat)abstract
- Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17 beta -oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone.
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- Berglin, Ewa, MD, PhD, 1955-, et al.
(författare)
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A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis
- 2004
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1465-9905. ; 6:4, s. R303-R308
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case–control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9–3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17–42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3–539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8–222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9–4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.
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- Cvetkovic, J T, et al.
(författare)
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Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis
- 2002
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Ingår i: Rheumatology. - 1462-0324 .- 1462-0332. ; 41, s. 988-995
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To analyse the association of autoantibodies against cardiolipin (CL) and oxidized low density lipoproteins [copper-oxidized low density lipoprotein (oxLDL), malondialdehyde-modified LDL (MDA-LDL)] with rheumatoid arthritis (RA) and cardiovascular complications. Methods. One hundred and twenty-one patients with RA were consecutively included. Autoantibodies were determined by ELISA. Healthy individuals from the same region were used as controls. Results. Levels of IgG, IgM and IgA antibodies against MDA-LDL and CL, as well as IgG and IgA antibodies against oxLDL were increased in the patients (P<0.01). The prevalence of IgG, IgM and IgA antibodies against CL was higher than in the normal population (74, 82 and 14%, respectively). The prevalence of IgG and IgA antibodies against oxLDL was also significantly increased (35 and 25%, respectively) and so was the prevalence of IgG and IgM antibodies against MDA-LDL (17 and 26%, respectively) compared with controls. The levels of IgM and IgA antibodies against aCL and IgM against MDA-LDL were increased in patients with extra-articular manifestations. Patients who developed myocardial infarction had a higher prevalence of IgG antibodies against MDA-LDL (P=0.04). There were substantial correlations between the levels of antibodies against oxLDL, MDA-LDL and CL. Conclusions. RA patients had increased levels and prevalence of autoantibodies against CL, oxLDL and MDA-LDL, with associations to severity of disease and cardiovascular complications.
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- Eriksson, Catharina, 1955-, et al.
(författare)
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Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus
- 2003
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 12:10, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Rantapää-Dahlqvist, Solbritt, et al.
(författare)
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Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis
- 2003
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Ingår i: Arthritis and Rheumatism. - : Wiley-Blackwell. - 0004-3591 .- 1529-0131. ; 48:10, s. 2741-2749
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Tidskriftsartikel (refereegranskat)abstract
- Methods: A case–control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti‐CCP antibody and RFs were determined using enzyme immunoassays.Results: Eighty‐three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1–4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti‐CCP, 16.9% for IgG‐RF, 19.3% for IgM‐RF, and 33.7% for IgA‐RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and ≤1.5 years before the appearance of any RA symptoms were 25% and 52% for anti‐CCP, 15% and 30% for IgM‐RF, 12% and 27% for IgG‐RF, and 29% and 39% for IgA‐RF. In conditional logistic regression models, anti‐CCP antibody and IgA‐RF were found to be significant predictors of RA.Conclusion: Anti‐CCP antibody and RFs of all isotypes predated the onset of RA by several years. The presence of anti‐CCP and IgA‐RF predicted the development of RA, with anti‐CCP antibody having the highest predictive value. This indicates that citrullination and the production of anti‐CCP and RF autoantibodies are early processes in RA.
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