Avidity of anti-phospholipid antibodies in relation to their levels.

INTRODUCTION: The heterogeneity of anti-phospholipid antibodies can be manifested not only in different antigenic specificities, but also in their avidities. The aim of the study was to investigate the relationship between anti-cardiolipin antibody (aCL) IgG avidities and levels within the range of their titres, from very low to high ones. MATERIAL AND METHODS: We analyzed 78 serum samples from 60 patients by ELISA with chaotropic agents, using urea concentration of 6 and 8 mol/l and single diluted serum samples. The changes of aCL levels and avidities were explored during a long-term follow-up in 14 patients. RESULTS: The avidities of aCLs did not differ in the groups of patients classified according to aCL levels. The higher avidity antibodies predominated in our patients and the fluctuation of avidities in the longitudinal follow-up did not show significant differences. No relationship between aCL levels and their avidities was found. CONCLUSIONS: aCL avidities seem to have no relationship with aCL levels and high-avidity aCLs; the potentially deleterious effects might be present also in patients with low and extremely low aCL levels. Avidity of aCLs belongs to stable characteristics with insignificant changes in time.

Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis.

Neurofilaments are cytoskeletal proteins localized within axons, which may interact with the immune system during and following tissue destruction in multiple sclerosis (MS). Antibodies against the medium neurofilament subunit synthesized intrathecally may reflect axonal damage in MS patients. Both immunoglobulin G (IgG) and M (IgM) responses against the purified native medium subunit of neurofilaments (NFM) using enzyme-linked immunosorbent assay (ELISA) were determined in paired serum and cerebrospinal fluid samples obtained from 49 MS patients, 16 normal controls (CN), 21 control patients with miscellaneous diseases (CD) and 14 patients with neurodegenerative disorders (CDEG). Intrathecal production of IgM and IgG antibodies to NFM were elevated in MS patients compared with the CN or CD groups (p<0.04 for IgM, p<0.01 for IgG). The increase was present in all the MS courses (relapsing-remitting, primary and secondary progressive). Similar local anti-NFM IgG and IgM synthesis occurred in the MS and CDEG groups. MS patients with short and long disease duration did not differ in terms of their anti-NFM IgM and IgG responses. Repeated examinations showed stable intrathecal anti-NFM production. Intrathecal IgG and IgM antibodies against NFM were increased in MS patients and may serve as a potential marker for axonal pathology. The extent of anti-NFM levels did not correspond to any individualized clinical profiles of MS patients.

Increased levels of pregnancy-associated plasma protein-A in patients with hypercholesterolemia: the effect of atorvastatin treatment.

BACKGROUND: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy. METHODS: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d). RESULTS: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 +/- 1.86 mU/L vs 6.50 +/- 2.54 mU/L, P =.018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels. CONCLUSIONS: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.

Serum and cerebrospinal fluid light neurofilaments and antibodies against them in clinically isolated syndrome and multiple sclerosis.

A release of light neurofilament subunits (NFL) into cerebrospinal fluid (CSF) and serum in multiple sclerosis (MS) may induce an immune response. We examined CSF and serum NFL levels and IgG antibodies against NFL in 19 patients with a clinically isolated syndrome (CIS) early converted into MS, 20 CIS-non-converters, 23 MS patients and 32 controls. CSF NFL levels were significantly higher in all patient groups. The highest CSF or intrathecally (IT) synthesized anti-NFL antibodies and CSF/serum ratios of anti-NFL antibodies were observed in CIS-converters. CSF NFL and CSF or IT anti-NFL antibodies could be surrogate biomarkers of axonal injury in early MS.

Increased intrathecal high-avidity anti-tau antibodies in patients with multiple sclerosis.

BACKGROUND: Antibodies against tau protein indicate an interaction between the immune system and the neurocytoskeleton and therefore may reflect axonal injury in multiple sclerosis (MS). METHODOLOGY/PRINCIPAL FINDINGS: The levels and avidities of anti-tau IgG antibodies were measured using ELISA in paired cerebrospinal fluid (CSF) and serum samples obtained from 49 MS patients and 47 controls. Anti-tau antibodies were significantly elevated intrathecally (p<0.0001) in the MS group. The CSF anti-tau antibody levels were lower in MS patients receiving therapy than those without treatment (p<0.05). The avidities of anti-tau antibodies were higher in the CSF than in the serum (MS group p<0.0001; controls p<0.005). Anti-tau avidities in the CSF were elevated in MS patients in comparison with controls (p<0.05), but not in serum. CONCLUSIONS: MS patients have higher levels of intrathecal anti-tau antibodies. Anti-tau antibodies have different avidities in different compartments with the highest values in the CSF of MS patients.

Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients.

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.

Intravenous iron gluconate administration increases circulating PAPP-A in hemodialysis patients.

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is a proatherosclerotic molecule, interrelated with oxidative stress in hemodialysis (HD) patients. As intravenous (IV) iron might enhance oxidative stress in HD patients, this study investigates circulating PAPP-A during HD session and after IV iron administration. METHODS: In 20 HD patients, plasma PAPP-A concentration was assessed immunochemically during 2 HD sessions (prior to HD and at 60, 130, and 240 min of HD session). Sodium ferric gluconate (62.5 mg) was given IV to all patients 65 min after the start of the second HD. RESULTS: Sixty-five min after IV iron application, there was a significant increase in plasma PAPP-A (from 36.0+/-9.9 to 79.6+/-28.9 mU/L, p<0.0001). At the end of this HD session, PAPP-A decreased significantly (p<0.0001), but still remained 1.5-fold greater compared with predialysis levels (p<0.0005). CONCLUSION: IV iron increases circulating PAPP-A, and in this way, it might contribute to more pronounced cardiovascular complications in HD patients.

Antiphospholipid antibodies in patients with lupus nephritis.

The aim of this study was to compare the prevalence of anticardiolipin antibodies with other types of antiphospholipid antibodies (aPL) (antiphosphatidylserine--aPS, antiphosphatidylinositol--aPI, antiphosphatidylethanolamine--aPE) in patients with lupus nephritis and to find if the examination of a panel of various aPL is valuable for further diagnosis of patients. Additionally we determined the levels of autoantibodies against beta2-glycoprotein I (beta2GPI) and oxidized low-density lipoprotein (anti-oxLDL) and also investigated the relationship between antibodies against beta2GPI and oxLDL, which were assessed by ELISA methods. Twenty-two patients with lupus nephritis were studied. The control group consisted of 62 healthy blood donors. A statistically significant higher occurrence of all aPLs in the patients with lupus nephritis in comparison to the control group was found. The prevalence of polyspecific antibodies, which reacted with at least two various phospholipids, was 82% in the group of SLE patients. Significantly higher levels of IgG anti-beta2GPI in the sera of SLE patients (p = 0.0003) was detected. The levels of anti-oxLDL in the sera of the patients group did not differ significantly from the control one. Some positive samples for anti-beta2GPI and negative for aCL or anti-oxLDL and vice versa were found. It ca be concluded that the production of aPL including anti-beta2GPI and anti-oxLDL in the lupus nephritis patients is higher in comparison with healthy blood donors. We assume that the estimation of various types of aPL may be important in the selection of the group patients with renal diseases. The synthesis of aPL can reflect the spreading of the autoimmune response for several antigens modified on the vessel wall.

Glycoxidation and inflammation in chronic haemodialysis patients.

BACKGROUND: Uraemia and haemodialysis treatment are associated with microinflammation and oxidative as well as carbonyl stress, which result in enhanced formation of glycoxidation products. Although both glycoxidation and inflammation can contribute to severe vascular and cardiovascular complications, the role that these pathogenic mechanisms play in the complex response of the whole organism remains to be elucidated. METHODS: We performed a cross-sectional study in 34 clinically stable chronic haemodialysis patients and in 14 healthy controls while determining serum concentrations of pentosidine, fluorescent advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs) and acute phase reactants. We further assessed the relationship between these glycoxidation products and parameters of inflammation. RESULTS: Glycoxidation products as well as certain acute phase reactants were elevated in haemodialysis patients. There were significant correlations between AOPPs and inflammatory parameters such as orosomucoid (0.39, P < 0.05), fibrinogen (0.49, P < 0.05) and pregnancy-associated protein A (PAPP-A; 0.46, P < 0.05), but no correlations between pentosidine or fluorescent AGEs and any of the inflammatory parameters. CONCLUSION: Oxidative damage showed a closer relationship to inflammation than advanced glycation (glycoxidation). AOPPs may represent a superior acute biochemical marker, whereas AGEs may better describe chronic long-lasting damage.