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- Akrawi, Delshad Saleh, et al.
(author)
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Heritability of glomerulonephritis : A Swedish adoption study
- 2019
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 49:8
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Journal article (peer-reviewed)abstract
- Background: Glomerulonephritis clusters in families. However, infections are common inducers of glomerulonephritis and may also cluster in families. Studies of adoptees and their biological and adoptive parents may disentangle genetic from environmental causes of familial clustering. This is the first adoption study aimed to estimate the genetic contribution to the familial transmission of glomerulonephritis. Materials and methods: We performed a family study for Swedish-born adoptees (born 1945–2000) and their biological and adoptive parents. The Swedish Multi-Generation Register was linked to the Hospital Inpatient Register for the period 1964–2012 and the Hospital Outpatient Register for 2001–2012. Odds ratio (OR) for glomerulonephritis was determined for adoptees with a biological parent with glomerulonephritis compared with adoptees without an affected biological parent. Similarly, the OR for glomerulonephritis was also determined in adoptees with an affected adoptive parent compared with adoptees without an affected adoptive parent. Heritability was estimated to be twice the observed tetrachoric correlation among adoptees and biological parents, under the assumption that only additive genetic factors contribute to the similarity between biological parents and adoptees. Results: The OR for glomerulonephritis was 4.08 in adoptees (95% confidence interval [CI] 1.79-9.27, P-value = 0.001) of biological parents diagnosed with glomerulonephritis. The OR for glomerulonephritis was 1.67 in adoptees (95% CI 0.53-5.26, P-value = 0.380) of adoptive parents diagnosed with glomerulonephritis. The heritability was 48%. Conclusion: Family history of glomerulonephritis in a biological parent is a risk factor for glomerulonephritis. The present study indicates that genetic factors play an important role in the aetiology of glomerulonephritis.
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- Al-Ani, Amer, et al.
(author)
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Low bone mineral density and fat free mass in young and middle-aged patients with a femoral neck fracture
- 2015
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 45:8, s. 800-806
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Journal article (peer-reviewed)abstract
- BackgroundReduced bone mineral density (BMD) together with muscle wasting and dysfunction, that is sarcopenia, emerges as a risk factor for hip fracture. The aim of this study was to examine body composition and BMD and their relationship with trauma mechanisms in young and middle-aged patients with femoral neck fracture.Materials and methodsAltogether, 185 patients with femoral neck fracture aged 20–69 were included. BMD, body composition and fat-free mass index (FFMI) were determined by dual-X-ray absorptiometry (DXA), and trauma mechanisms were registered.ResultsNinety per cent of the whole study population had a femoral neck BMD below the mean for age. In the young patients (< 50 years), 27% had a Z-score of BMD ≤ −2 SD. More than half of the middle-aged patients (50–69 years) had osteopenia, that is T-score −1 to −2·5, and 35% had osteoporosis, that is T-score < −2·5, at the femoral neck. Patients with low-energy trauma, sport injury or high-energy trauma had a median standardised BMD of 0·702, 0·740 vs. 0·803 g/cm2 (P = 0·03), and a median FFMI of 15·9, 17·7 vs. 17·5 kg/m2 (P < 0·001), respectively. FFMI < 10th percentile of an age- and gender-matched reference population was observed in one-third.ConclusionsA majority had low BMD at the femoral neck, and one-third had reduced FFMI (i.e. sarcopenia). Patients with fracture following low-energy trauma had significantly lower femoral neck BMD and FFMI than patients with other trauma mechanisms. DXA examination of both BMD and body composition could be of value especially in those with low-energy trauma.
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- Al-Ani, Amer N., et al.
(author)
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Low bone mineral density and fat-free mass in younger patients with a femoral neck fracture
- 2015
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 45:8, s. 800-806
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Journal article (peer-reviewed)abstract
- Background Reduced bone mineral density (BMD) together with muscle wasting and dysfunction, that is sarcopenia, emerges as a risk factor for hip fracture. The aim of this study was to examine body composition and BMD and their relationship with trauma mechanisms in young and middle-aged patients with femoral neck fracture. Materials and methods Altogether, 185 patients with femoral neck fracture aged 20-69 were included. BMD, body composition and fat-free mass index (FFMI) were determined by dual-X-ray absorptiometry (DXA), and trauma mechanisms were registered. Results Ninety per cent of the whole study population had a femoral neck BMD below the mean for age. In the young patients (<50years), 27% had a Z-score of BMD-2 SD. More than half of the middle-aged patients (50-69years) had osteopenia, that is T-score -1 to -25, and 35% had osteoporosis, that is T-score<-25, at the femoral neck. Patients with low-energy trauma, sport injury or high-energy trauma had a median standardised BMD of 0702, 0740 vs. 0803g/cm(2) (P=003), and a median FFMI of 159, 177 vs. 175kg/m(2) (P<0001), respectively. FFMI<10th percentile of an age- and gender-matched reference population was observed in one-third. Conclusions A majority had low BMD at the femoral neck, and one-third had reduced FFMI (i.e. sarcopenia). Patients with fracture following low-energy trauma had significantly lower femoral neck BMD and FFMI than patients with other trauma mechanisms. DXA examination of both BMD and body composition could be of value especially in those with low-energy trauma.
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- Barathan, Muttiah, et al.
(author)
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Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease
- 2015
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 45:5, s. 466-474
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Journal article (peer-reviewed)abstract
- BackgroundHepatitis C virus (HCV) causes persistent disease in similar to 85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses. Materials and methodsWe characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin. ResultsHCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells. ConclusionsChronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.
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- Barathan, Muttiah, et al.
(author)
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Peripheral loss of CD8(+)CD161(++)TCRV7 center dot 2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
- 2016
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In: European Journal of Clinical Investigation. - : WILEY-BLACKWELL. - 0014-2972 .- 1365-2362. ; 46:2, s. 170-180
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Journal article (peer-reviewed)abstract
- BackgroundMucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. Materials and methodsWe investigated the frequency of CD8(+)CD161(++)TCR V7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. ResultsThe frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. ConclusionsImmune exhaustion and senescence of CD8(+)CD161(++)TCR V7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.
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- Brinck, Jonas W., et al.
(author)
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High-density lipoprotein from end-stage renal disease patients exhibits superior cardioprotection and increase in sphingosine-1-phosphate
- 2018
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 48:2
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Journal article (peer-reviewed)abstract
- Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine-1-phosphate (S1P), HDL-associated S1P (HDL-S1P) and HDL-mediated protection against oxidative stress between CKD and control patients. Methods: High-density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL-S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin-induced oxidative stress in vitro were measured. Results: Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro-inflammatory cytokines (TNF-alpha and IL-6). Unexpectedly, HDL-S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL-S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively. Discussion: The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL-mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL-S1P.
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