High positivity of anti-CCP antibodies in patients with Down syndrome

The aim of the present study was to evaluate the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in patients with Down’s syndrome (DS) previously tested for IgM rheumatoid factor (RF) and to correlate the results with clinical findings. Eighty-eight patients with DS previously tested for IgM-RF were divided into two groups matched for sex and age. Group A consists of 42 RF positive patients and group B of 44 RF negative patients. The presence of anti-CCP antibody was determined using a second-generation enzyme-linked immunosorbent assay. A total of 52.3% (45/86) of DS patients were positive for anti-CCP antibodies. Twenty-four patients (57.1%) of the RF positive group and 21 (47.7%) of the RF negative group presented anti-CCP circulating antibodies. The concordance between both tests was 54.6%. None of the patients had clinical evidence of rheumatoid arthritis or juvenile idiopathic arthritis. Although a high prevalence of anti-CCP antibodies was observed in DS patients, no association has been found presently with clinical disease. Careful follow-up of these patients will be necessary to clarify the real significance of these findings.     

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD

Background and aimsSome previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD.Methods and resultsA total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77–11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30–7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3–F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype.ConclusionsSerum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.     

Association of ferritin and lipids with C-reactive protein

C-reactive protein (CRP) and lipids (e.g., low-density lipoprotein [LDL]) are both markers of cardiovascular disease risk, yet they are not highly correlated. Oxidative stress of lipids induced by iron may play a role in vascular inflammation, as indicated by CRP. The purpose of this study was to examine, in a representative sample of United States adults, the relation between ferritin, lipids, and CRP. We analyzed data on adults (aged > or =25 years) in the National Health and Nutrition Examination Survey III, a national public-use data set collected between 1988 and 1994. Ferritin, total cholesterol, LDL, high-density lipoprotein, and ferritin-lipid combinations were analyzed in relation to CRP in age-, gender-, and race-adjusted models as well as models with other potential confounding variables. In adjusted models, neither elevated ferritin (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.94 to 1.32) nor elevated LDL was significantly associated with elevated CRP (OR 1.03, 95% CI 0.79 to 1.33). Patients with elevated ferritin and elevated LDL were more likely to have elevated CRP (OR 1.68; 95% CI 1.06 to 2.68). Patients with elevated ferritin and low high-density lipoprotein were also more likely to have elevated CRP (OR 1.71; 95% CI 1.28 to 2.27). These results suggest that both iron and lipids induce inflammation. Future research needs to focus on preventive medicine to decrease iron in patients with elevated lipids.     

Association of ferritin antibodies with Takayasu arteritis

Takayasu arteritis (TA) is difficult to diagnose because diagnostic biomarkers have not yet been established. In a previous study, we detected autoantibodies against the human ferritin heavy chain protein (HFC) in the sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR). The aim of this study is to evaluate the frequency of autoantibodies against HFC in TA. We established seven ELISA assays for the detection of autoantibodies against HFC. We used the full-length recombinant HFC expressed in Escherichia coli or one of six different HFC peptides as autoantigens: 1-18Aa (98.8 % purity), 19-45Aa (98.8 % purity), 52-78Aa (98.3 % purity), 79-104Aa (98.8 % purity), 105-143Aa (98.4 % purity) and 145-183Aa (98.5 % purity). We collected sera from 48 patients with TA, 36 patients with systemic lupus erythematosus (SLE), 35 patients with arteriosclerosis, 133 patients with febrile diseases, which are known to generate unspecific autoantibodies, and 50 blood donors, which served as controls. The best results were obtained using the ferritin peptides as antigens. By combining the results from the different ELISAs that detect autoantibodies against the HFC peptides 19-44A, 79-104A and 105-144A, we were able to detect ferritin peptide antibodies in 30/48 (62 %) of the TA patients. The frequency was lower than in early GCA and PMR (previous study showed up to 92 %). Positive results were observed in 0/50 (0 %) of the control blood donors, 10/36 (28 %) of the SLE patients, 4/35 (11 %) of the arteriosclerosis patients and 27/133 (20 %) of the fever patients. Considering the lack of biomarkers for TA, autoantibodies against HFC peptides could act as useful markers for TA.     

Association between serum ferritin and circulating oxidized low-density lipoprotein levels in patients with type 2 diabetes

The oxidative modification of low-density lipoproteins (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Iron plays a part in the formation of highly toxic free radicals such as hydroxide and superoxide anions, which can induce lipid peroxidation. We investigated whether serum iron status was associated with circulating oxidized LDL (oxLDL) levels in type 2 diabetic patients, in whom oxidative stress and susceptibility to lipid oxidation were supposedly increased. Serum ferritin levels were significantly correlated with plasma oxLDL concentrations in both male and female patients (p<0.02 and p<0.05, respectively). No correlation was detected between ferritin and LDL-cholesterol (LDL-C) concentrations despite the close correlation between LDL-C and oxLDL concentrations (p<0.0001). Stepwise regression analysis showed that ferritin concentration was an independent positive determinant of oxLDL level, in addition to triglyceride concentration, body mass index and sex. This is the first report to show that serum ferritin is associated with circulating oxLDL levels in patients with type 2 diabetes. Further work is required to establish a causative link between iron excess and the development of diabetic vascular complications.     

Associations of serum iron and ferritin with hyperuricemia and serum uric acid

Clinical Rheumatology - To assess the serum iron and ferritin levels in relation to the prevalence of hyperuricemia (HU) and the serum uric acid (SUA) level. Serum iron and ferritin concentrations...     

Association between serum ferritin and the insulin resistance syndrome in a representative population

OBJECTIVE: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. METHODS: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. RESULTS: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. CONCLUSIONS: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.     

Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women

Increased serum ferritin concentrations in nonpathologic conditions, reflecting subclinical iron overload, have been reported to be associated with insulin resistance and an increased risk of type 2 diabetes mellitus (DM). However, serum ferritin concentrations differ significantly according to sex and ethnicity; and data concerning the relationship between serum ferritin concentrations and glucose metabolism abnormalities in Asian men and women are conflicting. This cross-sectional study investigated the association of serum ferritin concentrations with insulin resistance and impaired glucose metabolism in a large number of subjects with normal fasting glucose (NFG) level, impaired fasting glucose (IFG) level, or type 2 DM. We analyzed clinical and laboratory data from 12 090 subjects (6378 men and 5712 women; age, 20-89 years) who underwent general medical checkups. The study population included 1054 subjects with type 2 DM, 3783 subjects with IFG level, and 7253 subjects with NFG level. Serum ferritin, hemoglobin A_1c, fasting glucose, lipid, and insulin levels were measured. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. Serum ferritin concentrations were highest in the DM group, followed by the IFG group and the NFG group, in both men and women (186 ± 127, 176 ± 108, and 156 ± 92 ng/mL, respectively, in men; 85 ± 62, 75 ± 55, and 59 ± 47 ng/mL, respectively, in women). After adjustment for other variables using multiple regression analysis, homeostasis model assessment of insulin resistance was independently associated with serum ferritin concentration in men, but not in women. When the fourth quartile of ferritin was compared with the first quartile, the age-adjusted odds ratio (OR) for type 2 DM was 1.71 (95% confidence interval, 1.38-2.12) in men and 1.50 (1.05-2.13) in women. The OR in men was attenuated to 1.27 (1.01-1.60) but remained significant after adjustment for body mass index (BMI), waist circumference, blood pressure, serum lipids, liver enzymes, and high-sensitivity C-reactive protein (hsCRP). In nondiabetic subjects, the age-adjusted OR for IFG in the fourth quartile of ferritin was 1.82 (1.56-2.13) in men and 1.68 (1.40-2.02) in women. The OR was attenuated to 1.31 (1.11-1.55) in men and 1.45 (1.19-1.78) in women after adjustment for BMI, waist circumference, blood pressure, serum lipids, liver enzymes, and hsCRP. In NFG subjects, the age-adjusted OR for metabolic syndrome in the fourth quartile of ferritin concentration was 2.85 (1.99-4.07) in men and 1.21 (0.82-1.79) in women. In men, the OR was attenuated to 1.58 (1.06-2.37) after adjustment for BMI, liver enzymes, and hsCRP. Increased serum concentrations of ferritin are associated with insulin resistance, type 2 DM, IFG, and metabolic syndrome in men, but only with IFG in women. These results suggest that iron overload is associated with insulin resistance in men, but not in women.     

血清铁蛋白与动脉粥样硬化形成相关关系研究

目的探讨动脉粥样硬化高危人群血清铁蛋白水平与动脉粥样硬化形成的关系。方法随机抽选176例动脉粥样硬化高危患者,B型超声法测定其颈动脉内膜-中层厚度,观察斑块的有无并计算Crouse积分,作为评价动脉粥样硬化的指标。酶联免疫定量测定血清铁蛋白水平。结果根据颈动脉内膜-中层厚度≥0.8mm和(或)颈动脉粥样硬化斑块的形成分为颈动脉正常组和异常组。异常组血清铁蛋白较正常组明显升高(P<0.01),年龄也较正常组显著增加(P<0.01)。以血清铁蛋白≥300ng/ml为界分为血清铁蛋白升高组及正常组,发现升高组较正常组平均内膜-中层厚度、最大内膜-中层厚度及Crouse积分均显著升高(P<0.01,P<0.01,P<0.01)。直线相关与回归分析发现血清铁蛋白与平均内膜-中层厚度、最大内膜-中层厚度及Crouse积分之间均呈明显的正相关。结论血清铁蛋白水平升高与动脉粥样硬化呈正相关,进一步支持了“铁假说”。     

Elevated serum ferritin in children with malignancies.

Serum ferritin (SF) is elevated in adults with malignancies, chronic inflammatory disease, liver disease and iron overload. The purpose of this study was to determine whether the concentration of SF in children with a variety of malignancies correlated with the activity of their disease. Patients with acute lymphoblastic leukaemia (ALL) at initial diagnosis (n = 11) and relapse (n = 15) had a mean SF of 238 and 338 ng/ml, respectively, compared to the normal mean of 31 ng/ml and range of 7 to 140 ng/ml in children. In 30 patients with ALL in remission the mean SF was 109 ng/ml, less than the values in patients with active disease and greater than the normal mean (P less than 0.001). The concentration of SF was also increased in a group of 77 patients with a variety of solid tumors. The 28 cases with active disease had a mean SF of 242 ng/ml, significantly higher (P less than 0.001) that the value of 84 ng/ml in 49 patients with no evidence of residual tumor. The differences in SF concentration did reflect the activity of disease in the groups as a whole but it remains uncertain whether the assay will prove useful in following the response to treatment of patients with certain types of tumor.     

Association among serum ferritin, alanine aminotransferase levels, and metabolic syndrome in Korean postmenopausal women

We examined the relationships among serum ferritin, alanine aminotransferase (ALT) levels, and cardiovascular risk factors of metabolic syndrome in Korean postmenopausal women. We conducted a cross-sectional study of 959 postmenopausal women without an apparent cause of liver disease. Metabolic syndrome was defined as the presence of at least 3 of the following: elevated blood pressure, low high-density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Serum ferritin and ALT levels were found to be correlated (r=0.374, P<.001) and to be associated with the components of metabolic syndrome. Subjects with metabolic syndrome showed significantly higher serum ferritin (74.7+/- 2.0 vs 59.6+/- 2.0 ng/mL, P<.001) and ALT levels (21.3+/-1.6 vs 18.7+/-1.5 IU/L, P<.001). Moreover, the greater the number of metabolic syndrome components present, the higher were the serum ferritin and ALT levels (P<.001). Multiple regression analysis showed that serum ALT levels are significantly associated with serum ferritin levels, waist circumference, fasting blood glucose, age, and white blood cell count (adjusted R(2)=0.147). Elevated iron stores were positively associated with serum ALT levels and metabolic syndrome in Korean postmenopausal women.