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- Ajeganova, S, et al.
(författare)
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Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheroprotective natural antibodies for cardiovascular disease in early rheumatoid arthritis -- an inception cohort study
- 2012
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:6, s. 1146-1154
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Tidskriftsartikel (refereegranskat)abstract
- Although an enhanced risk of cardiovascular disease (CVD) in persons with rheumatoid arthritis (RA) is well established, the mechanisms behind it remain unclear. We studied whether carotid atherosclerosis, RA disease measures, or potential cardiovascular biomarkers influenced the incidence of CVD in an RA inception cohort.Methods.RA disease measures and CVD biomarkers were assessed at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography after 5 years. The study outcome was incident CVD events — acute myocardial infarction, angina pectoris, congestive heart failure, or ischemic cerebrovascular event. Survival analysis and Cox and longitudinal regressions were used for statistical analyses.Results.A total of 105 patients, without CVD events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35 events per 100 person-years (95% CI 0.71–2.0). The rate of CVD events did not differ with regard to measures of carotid intima-media thickness, but it was higher for patients with bilateral carotid plaques than for those without (p = 0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale for pain, and Stanford Health Assessment Questionnaire score over the first year, as well as usage of methotrexate (MTX), was associated, independent of age, with reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5–0.97), 0.97 (95% CI 0.95–0.99), 0.35 (95% CI 0.15–0.82), and 0.34 (95% CI 0.12–0.91), respectively]. In longitudinal analyses, increasing oxidized low-density lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies (anti-PC) were observed in those who experienced a subsequent CVD event.Conclusion.Bilateral carotid plaques were associated with poor CVD-free survival. Early reductions of inflammation, pain, and disability as well as MTX usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC levels may link chronic inflammation in RA to enhanced risk of CVD events.
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- Chen, X., et al.
(författare)
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A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
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