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- Corthay, Alexandre, et al.
(författare)
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Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis
- 1998
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Ingår i: European Journal of Immunology. - 1521-4141. ; 28:8, s. 2580-2590
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Tidskriftsartikel (refereegranskat)abstract
- Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire.
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- Michaëlsson, Karl, 1959-, et al.
(författare)
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Effect of prefracture versus postfracture dietary assessment on hip fracture risk estimates
- 1996
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 25:2, s. 403-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Dietary factors are presumed to have influence on bone mass and hence fracture susceptibility. Most information in this respect is based on retrospective assessment of previous dietary habits. In a population-based case-control study nested within a cohort, we collected dietary information both before and after a first hip fracture. Thus it was possible to study reported changes in dietary habits, intentional as well as unintentional, among hip fracture patients after a first hip fracture and to compare postfracture with prefracture dietary information. METHODS. More than 65 000 women born 1914-1948 in two counties in central Sweden completed a food frequency questionnaire regarding their usual current dietary habits, before attending a mammographic screening between the years 1987 and 1990. Subsequently 123 of them sustained a first hip fracture and were defined as cases in the present study. For every case, one control, individually matched by age and county of residence, was selected from the cohort. A second identical food frequency questionnaire was mailed to both cases and controls on average 2 years after the hip fracture event. In total 98 case/control pairs could be included in the analysis. The association between diet and hip fracture was evaluated and the results from the two dietary assessments were contrasted. Women who themselves claimed that they had not changed their diet in recent years were analysed separately. RESULTS. The hip fracture cases, compared with the controls, had reduced their reported dietary intake of dairy products after the fracture. Apparently this was not intentional since this effect was more pronounced among those cases who claimed that their diet was unchanged. The changes were most apparent among the younger cases with a more recent hip fracture and with a body mass index above the median. Half of the cases, more than twice the frequency in controls, who were initially classified as having high intake of dairy products were classified as having low intake (<800 mg calcium/day) after the hip fracture. This also lowered, in fact reversed, the relative risk estimates of hip fracture both for intake of dairy products and calcium. Crude odds ratios of highest quartile of intake versus lowest, changed from 3.0 to 0.6 for dairy products and from 2.6 to 0.9 for calcium. No other foods or nutrients displayed such notable differences between the two surveys. CONCLUSION. We conclude that the use of current and retrospective dietary information after a hip fracture can lead to a differential misclassification in dietary studies and to biased estimates of hip fracture risk as compared with prospectively collected dietary information.
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- Michaëlsson, Karl, 1959-, et al.
(författare)
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Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture
- 1998
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 8:6, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.
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