The Twilight of Cutting: African Activism and Life after NGOs by Saida Hodzic Oakland, CA: University of California Press, 2017. Pp. 416. $34.95 (pbk) (original) (raw)
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Anti-High-Density Lipoprotein Antibodies and Antioxidant Dysfunction in Immune-Driven Diseases
Frontiers in medicine, 2018
Impaired high-density lipoprotein (HDL) levels and antioxidant functionality of HDL, mainly attributed to a decreased paraoxonase-1 (PON1) functionality, have been described in autoimmune conditions. In this setting, a role for humoral response in cardiovascular disease is emerging. This study evaluates the role of immunoglobulin G (IgG) antibodies against HDL and disease-related autoantibodies on HDL dysfunction in immune-driven diseases. Serum IgG anti-HDL antibodies, PON1 activity, and total antioxidant capacity (TAC) were quantified in 381 patients with different immune-driven diseases [18 mixed connective tissue disease (MCTD), 35 primary Sjögren syndrome (pSS), 38 systemic sclerosis (SSc), 33 ANCA-associated vasculitis (AAV), 60 diabetes mellitus 1, 29 autoimmune B12 deficiency/pernicious anemia, 29 primary biliary cirrhosis, 46 IBD/Crohn, 54 IBD/UC, and 39 celiac disease (CD)] and 138 healthy controls. IgG anti-HDL antibodies were increased in MCTD, pSS, AAV, and inflammatory...
Arthritis and Rheumatism, 2002
ObjectiveTo determine the prevalence of anti–high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti–β2-glycoprotein I (anti-β2GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS).To determine the prevalence of anti–high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti–β2-glycoprotein I (anti-β2GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS).MethodsThirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-β2GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL2, and HDL3 were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence.Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-β2GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL2, and HDL3 were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence.ResultsLevels of total HDL, HDL2, and HDL3 were reduced in patients with SLE compared with controls (mean ± SD 0.51 ± 0.3, 0.37 ± 0.3, and 0.14 ± 0.1 mmoles/liter, respectively, versus 1.42 ± 0.9, 1.01 ± 0.7, and 0.40 ± 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = −0.48, P = 0.005) whereas in the primary APS population, IgG anti-β2GPI was the only independent predictor of PON activity (r = −0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = −0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02).Levels of total HDL, HDL2, and HDL3 were reduced in patients with SLE compared with controls (mean ± SD 0.51 ± 0.3, 0.37 ± 0.3, and 0.14 ± 0.1 mmoles/liter, respectively, versus 1.42 ± 0.9, 1.01 ± 0.7, and 0.40 ± 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = −0.48, P = 0.005) whereas in the primary APS population, IgG anti-β2GPI was the only independent predictor of PON activity (r = −0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = −0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02).ConclusionIgG anti-HDL and IgG anti-β2GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.IgG anti-HDL and IgG anti-β2GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.
Rheumatology, 2008
Objective. To determine whether antibodies against high-density lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with the anti-atherogenic functions of high-density lipoprotein (HDL) and relate to disease activity and damage in SLE. Methods. Seventy-seven SLE patients were compared with an age-and sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG aApoA-I, soluble vascular cell and intracellular cell adhesion molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA, paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx) metabolites by the Griess reaction, and total anti-oxidant capacity (TAC) by chemiluminescence. Results. Compared with controls, SLE patients showed higher titres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P < 0.0001), lower PON activity (P < 0.0001), increased NOx (P < 0.0001), VCAM-1 (P < 0.0001) and ICAM-1 (P ¼ 0.0008) and lower TAC (P ¼ 0.0006). Titres of IgG aHDL positively correlated with IgG aApo A-I (r ¼ 0.64, P < 0.0001), NOx (r ¼ 0.32, P ¼ 0.007), inversely correlated with PON activity (r ¼ À0.34, P ¼ 0.002) and TAC (r ¼ À0.43, P ¼ 0.0004) and were independently associated with ICAM-1 (t ¼ 3.509, P ¼ 0.001). IgG aApo A-I titres correlated positively with NO (r ¼ 0.37, P ¼ 0.007), inversely with PON activity (r ¼ À0.31, P ¼ 0.006), TAC (r ¼ À0.47, P < 0.0001) and were independently associated with HDL (t ¼ À2.747, P ¼ 0.008) and VCAM-1 (t ¼ 3.311, P ¼ 0.002), the latter alongside NOx (T ¼ 2.271, P ¼ 0.02). Elevated titres of IgG aHDL and IgG aApo A-I and reduced PON activity related to increased disease score (BILAG) and damage index (SLICC/ACR DI). Conclusion. In SLE, IgG aHDL and aApo A-I associate with disease activity and damage and interfere with the anti-oxidant and antiinflammatory functions of HDL favouring atherogenesis.
Ethnic variation in levels of circulating IgG autoantibodies to oxidised low-density lipoprotein
Atherosclerosis, 2009
Background: Oxidised low-density lipoprotein (Ox-LDL) plays a key role in atherosclerosis. Our aim was to determine whether serum autoantibodies against Ox-LDL (Ab Ox-LDL) differ by ethnic group. Design and methods: Soluble serum Ab Ox-LDL levels were measured in 250 white (113 females), 169 African origin (91 females) and 196 South Asian (92 females) individuals from the Wandsworth Heart and Stroke Study (WHSS) population. All were free from coronary heart disease (CHD), stroke, other cardiovascular disease, diabetes, drug therapy for hypertension or high lipids, hormone replacement therapy or oral contraceptive pill. Results: There were no sex differences in levels of Ab Ox-LDL, but levels were higher in non-smokers (430 U/L [95% CI 471-596]) than in smokers (384 U/L [316-468]) (p < 0.009). Age-and sex-adjusted levels of Ab Ox-LDL were higher in people of African origin and South Asians compared to whites. This difference was maintained in South Asian women following adjustment for multiple risk factors (82% ; p = 0.004). Ab Ox-LDL levels were negatively associated with serum triglycerides and positively associated with sVCAM-1. Conclusions: Higher IgG Ab to Ox-LDL are associated with higher levels of sVCAM-1 and, are elevated in female South Asian individuals who have an increased risk of atherosclerosis compared to whites.
Clinica Chimica Acta, 2009
Background: Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS). Methods: Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n = 94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n = 116). Autoantibodies against copper ion oxidized LDL were measured by enzymelinked-immunosorbent assay. Results: Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p b 0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r=−0.284), body mass index (r=−0.256), waist circumference (r=−0.368), apolipoprotein B (r=−0.191), glucose (r=−0.303), systolic blood pressure (r=0.319), diastolic blood pressure (r= 0.167), high-density lipoprotein cholesterol (r=0.224) and apolipoprotein A1 (r=0.257) (pb 0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL. Conclusions: Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis.
Thrombosis and haemostasis, 2017
The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC (p < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were signific...
Diabetes, 2000
We investigated the hypothesis that modified lipoproteins trigger an immune response leading to the production of autoantibodies and subsequently to the formation of atherogenic immune complexes (IC). We recruited 20 type 2 diabetic patients with macrovascular disease, 14 nondiabetic patients with coronary artery disease (CAD), and 34 healthy control subjects matched for age, sex, and race. Serum antibodies to oxidized and glycated LDL did not differ significantly among the 3 groups. Serum IC contained variable, but not statistically different, amounts of IgG, IgM, and IgA. In contrast, the content of cholesterol in IC isolated from diabetic patients was significantly higher than that in IC isolated from control subjects, and the content of apolipoprotein (apo)-B was significantly higher than that in IC isolated from control subjects and patients with CAD. Cholesteryl ester accumulation in human monocyte-derived macrophages incubated with IC, a measure of the atherogenic potential o...
Metabolic syndrome, autoimmunity and rheumatic diseases
Pharmacological research, 2018
Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular (CV) risk factors including obesity and visceral adiposity, insulin resistance, dyslipidemia and hypertension contributing to CV mortality. The interface between the metabolic and immune systems has been of great interest recently. These interactions are regulated through genetics, nutritional status, and the intestinal microbiome. Alterations in the immune-metabolic cross-talk contribute to the development of autoimmune diseases. Adipokines exert a variety of metabolic activities contributing to the ethiopathogenesis of MetS and are involved in the regulation of both inflammatory processes and autoimmunity occurring in rheumatic diseases. Patients with autoinflammatory disease such as gout and those with autoimmune rheumatic diseases (ARD), such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ankylosing spondylitis and vasculitis among others, have increased prevalence of MetS. ...