| 21. |
- Samal, Shailesh Kumar, et al.
(författare)
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Potential natural immunization against atherosclerosis in hibernating bears
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Brown bears (Ursus arctos) hibernate for 5-6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9-107.9) vs 782.3, IQR (422.8-1586.0; p < 0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis.
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| 22. |
- Sjöberg, Beatrice G., et al.
(författare)
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Low levels of IgM antibodies against phosphorylcholine : a potential risk marker for ischemic stroke in men
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 203:2, s. 528-532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Natural antibodies specific for phosphorylcholine (anti-PC) have been implicated as protective factors in atherosclerosis. We herein determined the relationship between IgM anti-PC and incidence of cardiovascular disease (CVD). METHODS: We studied 349 incident cases (200 men) of first events of CVD (coronary heart disease (CHD; n=203 or ischemic stroke; n=146) and 693 age- and sex-matched controls identified through 12 years of follow-up (1991-2003) of subjects from the cardiovascular cohort within the Malmö Diet and Cancer Study. Relative risks (RR) of CVD with 95% confidence intervals (CI) of incident CVD with adjustments for age, smoking, total cholesterol and blood pressure were determined. Anti-PC-levels were measured using ELISA (Athera CVDefine). RESULTS: As determined using Athera CVDefine, significant associations were attained with values of anti-PC below 17U/ml (corresponding to the lowest 9th percentile), which remained after taking confounders into account (RR: 1.79, 95% CI: 1.09-2.94, p=0.021). If men were studied separately, significance was evident at values below 17U/ml (RR: 2.01, 95% CI: 1.11-3.67, p=0.022), which was not the case among women. Furthermore, values below 17U/ml were also associated with ischemic stroke (RR=3.67, 95% CI: 1.34-10.1, p=0.01), but not with CHD. CONCLUSION: Low IgM anti-PC could be a novel risk marker for development of ischemic stroke in men. Further studies are needed to establish gender and subgroup differences.
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| 23. |
- Sjöwall, Christopher, 1975-
(författare)
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C-reactive protein (CRP) and anti-CRP autoantibodies in systemic lupus erythematosus : a study on the occurrence and clinical implications of anti-CRP antibodies and CRP-mediated complement activation
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of a wide range of autoantibodies, multiple organ involvement and by local formation or tissue deposition of immune complexes (ICs) in the inflamed organs. In contrast to most systemic inflammatory conditions, and despite raised levels of pro-inflammatory cytokines, SLE flares are rarely reflected by elevated C-reactive protein (CRP), an important acute-phase reactant in man with homologs in vertebrates and several invertebrates. As a part of the innate immune system, CRP binds certain molecules exposed on the surface of dying cells/apoptotic bodies and on the surface of pathogens and mediates their elimination by uptake in the reticuloendothelial system. CRP also interacts with IgG-containing immune complexes, binds Fc receptors and activates the complement system via C1q.The aims of this thesis were to investigate the complement activation properties of CRP; to elucidate if anti-CRP antibodies occur in SLE and, if so, whether anti-CRP antibody levels correlate with disease activity in SLE; to test the hypothesis that autoantibodies to pro-inflammatory cytokines prevent rise of CRP; and to survey if autoantibodies to certain nuclear antigens or to CRP correlate with cytokine-inducing properties of ICs from SLE sera.We have demonstrated that CRP bound to phosphorylcholine is a powerful activator of the classical complement pathway already in the CRP concentration range 4 to 10 mg/L, but with a marked inhibition at CRP levels above 150 mg/L. Autoantibodies to the monomeric form of CRP were found in approximately 40 percent of SLE patients and in a few sera from patients with primary Sjögren’s syndrome, but not in rheumatoid arthritis or in inflammatory bowel disease. The anti-CRP antibody levels showed significant correlations to several laboratory and clinical measurements, and anti-CRP positivity was associated with renal involvement in SLE. Native CRP levels were not correlated with anti-CRP or anti-cytokine antibody levels. Hence, the presence of antibodies to monomeric CRP or to CRP-inducing cytokines is an unlikely explanation to the relative failure of CRP response in patients with active lupus. However, antibodies to TNFα were found in subnormal levels at disease flares, whereas antibodies to TGFβ were found in supranormal levels as compared to healthy subjects. In contrast to antibodies against CRP and DNA, anti-SSA and anti-SSB antibodies may regulate the inflammatory process in SLE by enhancing IC formation and subsequent production of cytokines such as IL-6, IL-10 and IL-12p40. Hypothetically, anti-CRP autoantibodies may be of pathogenic importance, for instance by binding to monomeric CRP on cell and tissue surfaces and thereby increasing the risk of extrahepatic deposition of apoptotic material and in situ formation of ICs.
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| 24. |
- Stenvinkel, Peter, et al.
(författare)
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NATURAL IMMUNISATION AGAINST ATHEROSCLEROSIS IN BEARS DURING HIBERNATION
- 2021
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 36:Suppl. 1, s. 283-283
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND AND AIMS: Brown bears (Ursusarctos) hibernate for 5-6 months during winter, but in spite of kidney insufficiency, dyslipidemia, insulin resistance and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). Antibodies against phosphorylcholine (anti-PC) are associated with protection in atherosclerosis, CVD and uremia. Potential underlying protective mechanisms include anti-inflammatory effects, inhibition of cell death, promotion of T regulatory cells, clearance of dead cells and inhibition of oxidized Low density lipoprotein (OxLDL)-uptake in macrophages in atherosclerotic plaques. PC is an important antigen on nematodes, parasites, some bacteria, dead and dying cells and OxLDL.METHOD: Paired serum from 12 brown bears sampled during winter and summer were analyzed for metabolic parameters and for IgM, IgG, IgG1/2 and IgA anti-PC by enzyme linked immunosorbent assay (ELISA). Differences in antibody levels between winter and summer were determined by paired Students t test or Wilcoxons signed rank test (when not normally distributed).RESULTS: As expected, marked differences in metabolic parameters were found comparing median summer vs winter values; Cholesterol 5.9 vs 11.3 mmol/L; p<0.001, triglycerides 1.9 vs 3.7 mmol/L; p<0.001, glucose 5.4 vs 7.7 mmol/L; p<0.05, S-creatinine 76 vs 203 mmol/L; p<0.001, urea 12.1 vs 2.9 mmol/L; p<0.002. When determined as arbitrary units (AU; median set at 100 at summer), marked and significant differences were observed between summer and winter.CONCLUSION: Anti-PC (strikingly so for IgA and IgG1) are significantly raised during hibernation as compared to levels during summer. We hypothesize that these changes contribute to the protection of arteries, but also kidneys and other organs, during the metabolic vulnerable hibernation period. Our observation may represent a natural immunization with microorganisms, preventing atherosclerosis during a period of severe kidney insufficiency and could have therapeutic implications for patients with chronic kidney disease.
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| 25. |
- Waldheim, Eva, et al.
(författare)
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Extent and characteristics of self-reported pain in patients with systemic lupus erythematosus
- 2013
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Ingår i: Lupus. - London : Sage Publications. - 0961-2033 .- 1477-0962. ; 22:2, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients' own experiences of subjective symptoms are scarcely covered, and the objective of this study was to investigate the extent and characteristics of self-reported pain in patients with systemic lupus erythematosus (SLE).METHODS: This study comprised a cross-sectional design where 84 patients with SLE were asked to complete self-assessments: visual analogue scale of pain and the Short-Form McGill Pain Questionnaire. Medical assessments, including ESR, SLAM, SLEDAI, and SLICC, were also performed.RESULTS: Of the study population, 24% reported higher levels of SLE-related pain (≥40 mm on VAS). This group had a significantly shorter disease duration, higher ESR, and higher disease activity, according to the SLAM and SLEDAI, compared to the rest of the study population. This group mainly used the words "tender," "aching," and "burning" to describe moderate and severe pain, and they used a greater number of words to describe their pain. Of the patients with higher levels of pain, 70% reported their present pain as "distressing." The most common pain location for the whole patient population was the joints. Patients rated their disease activity significantly higher than physicians did.CONCLUSION: These findings expand the current knowledge of the extent of SLE-related pain and how patients perceive this pain. The results can contribute to affirmative, supportive and caring communication and especially highlight SLE-related pain in patients with a short disease duration and high disease activity.
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| 26. |
- Waldheim, Eva, et al.
(författare)
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Health-related quality of life, fatigue and mood in patients with SLE and high levels of pain compared to controls and patients with low levels of pain
- 2013
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Ingår i: Lupus. - London : Sage Publications. - 0961-2033 .- 1477-0962. ; 22:11, s. 1118-1127
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this paper is to investigate health-related quality of life (HRQoL), fatigue, anxiety and depression in patients with systemic lupus erythematosus (SLE) and higher levels of pain and to compare them to patients with lower levels of pain and controls.Method: Patients were dichotomized into two groups based on SLE-related pain score on the visual analog scale (VAS): low-pain group (76%, n=64, VAS 0-39 mm) and high-pain group (24%, n=20, VAS 40-100 mm). Sex- and age-matched controls were randomly selected from the general population. Participants were asked to complete questionnaires regarding self-reported pain, HRQoL, fatigue, anxiety and depression. Medical assessments also were recorded.Result: Fatigue score in the high-pain group (median, 36.5; interquartile range (IQR), 32.5-39.7) was significantly higher (p<0.001) compared to the low-pain group (median, 23; IQR, 14.6-34.1), as well as scores for anxiety (median, 9; IQR, 6.5-11.5) and depression (median, 7.5; IQR, 5.5-9) (p<0.001). The high-pain group had significantly lower scores compared to the low-pain group in all dimensions in the SF-36 (p ≤ 0.001-0.007). No statistical differences were detected between the low-pain group and controls in any measurement except for the dimensions physical function, general health, vitality and social function in SF-36. Conclusion Patients with SLE scoring higher degrees of pain were burdened with more fatigue, anxiety and depression and lower levels of HRQoL compared to patients with lower levels of pain who did not differ significantly from the general population in most dimensions. These results elucidate the importance of identifying patients with higher degrees of pain who are probably in need of more extensive multidimensional interventions to decrease symptom burden.
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