| 11. |
- Elkan, Ann-Charlotte, et al.
(författare)
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Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis : a cross-sectional study
- 2009
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:2, s. R37-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA. METHODS: A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined. RESULTS: The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001). CONCLUSIONS: About one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD.
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| 12. |
- Fiskesund, Roland, et al.
(författare)
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Low levels of antibodies against phosphorylcholine predict development of stroke in a population-based study from northern Sweden
- 2010
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 41:4, s. 607-612
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Natural immunoglobulin M antibodies specific for phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have shown previously that high levels of anti-PC predict a slower progression of atherosclerosis in humans and that low levels of anti-PC are associated with higher risk for cardiovascular disease. Here we determine the association between anti-PC and the incidence of stroke. METHODS: Using a nested case control study design, we examined 227 incident cases (125 men and 102 women) of first-time stroke and 455 age- and sex-matched controls identified during a 13-year time period (1985 to 1999) within the population-based cohorts of the Västerbotten Intervention Project (VIP) and the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender, smoking, serum cholesterol, diabetes, body mass index, and blood pressure were determined. Anti-PC levels were measured using ELISA. RESULTS: A significant association between low levels of anti-PC at baseline and incident stroke was seen for the whole group of anti-PC levels below the 30th percentile (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender-specific associations indicated fairly strong associations for females, especially at the lowest 30th percentile (multivariately adjusted odds ratio, 2.65; CI, 1.41 to 4.95). No associations were noted for men. CONCLUSION: Low anti-PC is a novel independent risk marker for development of stroke. Measurements of anti-PC could be used to identify immunodeficient subjects at an increased risk for stroke. The possibility that such subjects might be targets for novel modes of treatment such as immunotherapies deserves further investigation.
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| 13. |
- Frostegård, Johan, et al.
(författare)
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Antibodies against Phosphorylcholine among New Guineans Compared to Swedes: An Aspect of the Hygiene/Missing Old Friends Hypothesis.
- 2017
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Ingår i: Immunological investigations. - : Informa UK Limited. - 1532-4311 .- 0882-0139. ; 46:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- We here study antibodies against phosphorylcholine (anti-PC) which we reported to be inversely associated with atherosclerosis, cardiovascular disease (CVD), and autoimmune conditions. In previous studies, we determined that this inverse association is more pronounced at low levels with high risk and at high levels, with decreased risk. We compare individuals from Kitava, New Guinea (with low risk of these conditions), with Swedish controls.We studied a group of 178 individuals from Kitava (age 20-86), and compared those above age 40 (n = 108) with a group of age- and sex-matched individuals from a population based cohort in Sweden (n = 108). Traditional risk factors for CVD and fatty acids were determined. IgM, IgG, and IgA anti-PC were tested by enzyme-linked immunosorbent assay (ELISA).All anti-PC measures were significantly lower among Swedish controls as compared to Kitavans (p < 0.001), independent of traditional risk factors. Having low levels of anti-PC, defined as below 25th percentile of values among Swedish controls, was associated with this cohort after adjustment for other risk factors (OR 5.7, 95% CI 2.2-14.7 for IgM; OR 31.7, 95% CI 3.9-252 for IgA; and OR 11.1, 95% CI 2.4-51 for IgG).PC is highly exposed on microorganisms and helminths (common on Kitava) exposing much PC which humans and hominids may have been exposed to for millions of years. We propose that low anti-PC levels in the developed world could be a new aspect of the hygiene hypothesis, generating a pro-inflammatory and pro-atherosclerotic state.
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| 14. |
- Grönlund, Hans, et al.
(författare)
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Low levels of IgM antibodies against phosphorylcholine predict development of acute myocardial infarction in a population-based cohort from northern Sweden.
- 2009
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Sage. - 1741-8267 .- 1741-8275. ; 16:3, s. 382-386
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Phosphorylcholine (PC) is one important epitope on oxidized low-density lipoprotein that may play an important role by contributing to the atherogenicity of oxidized low-density lipoprotein. IgM antibodies against PC (anti-PC) are present ubiquitously in the population as natural antibodies. We here determine the association between anti-PC and incidence of myocardial infarction (MI). METHODS: We studied 462 incident cases of first events of MI and 888 age-matched and sex-matched controls identified through 13 years of follow-up (1987-1999) of participants in a population-based study from northern Sweden. Relative risks (RRs) with 95% confidence intervals (CIs) of incident MI with adjustments for age, sex, geographical region, hypertension, diabetes, BMI, smoking habits, s-cholesterol and high-sensitivity C-reactive protein were determined. Anti-PC levels were measured by enzyme-linked immunoassay. RESULTS: Low anti-PC values were associated with increased risk of MI. Significant associations were found for values below 26.8 U/ml, corresponding to the lowest 25th percentile, and the highest association was seen below 16.9 U/ml. These results remained almost the same after adjustment for confounding factors (RR crude: 1.56, CI: 1.07-2.28 and RR adjusted: 1.69, CI: 1.09-2.54). CONCLUSION: Low levels of natural IgM anti-PC could play an important role as risk markers for development of MI. Adjustment for common confounders only marginally affected the RR, suggesting that the addition of IgM anti-PC add independent information to the more traditional risk factors.
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| 15. |
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| 16. |
- Jujic, Amra, et al.
(författare)
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Antibodies against phosphorylcholine in hospitalized versus non‑hospitalized obese subjects
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m2) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33–0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.
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| 17. |
- Jönsson, Tommy, et al.
(författare)
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A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs.
- 2006
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Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 3:Article nr. 39
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Tidskriftsartikel (refereegranskat)abstract
- A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed.
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| 18. |
- Löfgren, Sara E., et al.
(författare)
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A 3 '-Untranslated Region Variant Is Associated With Impaired Expression of CD226 in T and Natural Killer T Cells and Is Associated With Susceptibility to Systemic Lupus Erythematosus
- 2010
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:11, s. 3404-3414
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association. Methods. Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments. Results. A 3-variant haplotype, rs763361; rs34794968; rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 x 10(-4), odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts. Conclusion. This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells.
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| 19. |
- Paramel Varghese, Geena, 1985-
(författare)
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Innate immunity in human atherosclerosis and myocardial infarction : Role of CARD8 and NLRP3
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is complex inflammatory disease of the arterial wall with progressive accumulation of lipids and narrowing of the vessel. Increasing evidence suggest that inflammation plays an important role in plaque stability and often accelerate cardiovascular events such as myocardial infarction (MI). Among the vast number of inflammatory cytokines, IL-1β is known to be a key modulator in vessel wall inflammation and acceleration of the atherosclerotic process. The biologically active IL-1β is regulated by a multiprotein complex known as the NLRP3 inflammasome complex. In this thesis, we have focused on polymorphisms in the NLRP3 and CARD8 genes and their possible association to atherosclerosis and/or MI. We have also investigated the expression of inflammasome components NLRP3 and CARD8 in atherosclerosis and the role of genetic variants for the expression of these genes. The expression of NLRP3, CARD8, ASC, caspase-1, IL-1β, and IL-18 were found significantly upregulated in atherosclerotic lesions compared to normal arteries. Human carotid plaques not only express the NLRP3 inflammasome, but also release IL-1β upon exposure to lipopolysaccharide (LPS), adenosine triphosphate (ATP) and cholesterol crystals, which suggest NLRP3 inflammasome activation in human atherosclerotic lesions. Also, CARD8 was found to be important in the regulation of several inflammatory markers in endothelial cells, like RANTES, IP10 and ICAM-1. We further assessed the potential association of a CARD8 polymorphism and polymorphisms located downstream of the NLRP3 gene to the risk of MI in two independent Swedish cohorts. The CARD8 variant exhibited no association to risk of MI in either of the two cohorts. Some of the minor alleles of NLRP3 variants were associated with increased IL-1β levels and to NLRP3 mRNA levels in peripheral blood monocytic cells (PBMC). Taken together, the present thesis shows that NLRP3 inflammasome activation and increased expression of CARD8 in the atherosclerotic plaque might be possible contributors to the enhanced inflammatory response and leukocyte infiltration in the pathophysiology of atherosclerosis.
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| 20. |
- Pockley, A., et al.
(författare)
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Circulating heat shock protein and heat shock protein antibody levels in established hypertension.
- 2002
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Ingår i: Journal of Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 1473-5598 .- 0263-6352. ; 20:9, s. 1815-1820
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Serum Hsp60 and anti-Hsp65 antibody levels are raised in subjects with borderline hypertension, and there is an association between circulating Hsp60 levels and early atherosclerosis. Given the recognized relationship between hypertension and atherosclerosis, this study determined heat shock protein and heat shock protein antibody levels in subjects with established hypertension.METHODS Samples from 111 men with hypertension were obtained from the European Lacidipine study on Atherosclerosis and samples from 75 normotensive controls were taken from a population-screening programme (diastolic pressure, 95 and 80 mmHg, respectively). Hsp60, Hsp70 and anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. Intima-media thickness (I-M) and the presence of carotid atherosclerosis were determined by ultrasonography.RESULTS Hsp60, Hsp70 and anti-Hsp60 antibody levels in hypertension were similar to those in normotensive controls, whereas anti-Hsp70 and anti-Hsp65 antibody levels were elevated ( 0.001). Hsp60 levels and atherosclerosis were not associated. Anti-Hsp70 and anti-Hsp65 antibody levels were both associated with hypertension, independently of age, smoking habits and blood lipids.CONCLUSIONS This study demonstrates elevated levels of selected heat shock protein antibodies in subjects with hypertension. Although the association between heat shock protein antibody levels and human cardiovascular stress/disease appears to be robust, the relationship of the latter with heat shock protein levels is more complex. Further studies are required before the factors inducing, and the clinical significance of, circulating heat shock proteins can be evaluated.
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