AADvac1, an Active Immunotherapy for Alzheimer's Disease and Non Alzheimer Tauopathies: An Overview of Preclinical and Clinical Development.

Neurofibrillary tau protein pathology is closely associated with the progression and phenotype of cognitive decline in Alzheimer's disease and other tauopathies, and a high-priority target for disease-modifying therapies. Herein, we provide an overview of the development of AADvac1, an active immunotherapy against tau pathology, and tau epitopes that are potential targets for immunotherapy. The vaccine leads to the production of antibodies that target conformational epitopes in the microtubule-binding region of tau, with the aim to prevent tau aggregation and spreading of pathology, and promote tau clearance. The therapeutic potential of the vaccine was evaluated in transgenic rats and mice expressing truncated, non mutant tau protein, which faithfully replicate of human tau pathology. Treatment with AADvac1 resulted in reduction of neurofibrillary pathology and insoluble tau in their brains, and amelioration of their deleterious phenotype. The vaccine was highly immunogenic in humans, inducing production of IgG antibodies against the tau peptide in 29/30 treated elderly patients with mild-to-moderate Alzheimer's. These antibodies were able to recognise insoluble tau proteins in Alzheimer patients' brains. Treatment with AADvac1 proved to be remarkably safe, with injection site reactions being the only adverse event tied to treatment. AADvac1 is currently being investigated in a phase 2 study in Alzheimer's disease, and a phase 1 study in non-fluent primary progressive aphasia, a neurodegenerative disorder with a high tau pathology component.

Avidity of selected autoantibodies - usefulness of their determination for clinical purposes.

Autoantibodies directed against various self-antigens comprise a heterogeneous group of immunoglobulins, which differ in their qualitative and quantitative features. An important qualitative characteristic of antibodies is affinity/avidity, which changes in the process of its maturation during the immune response.This study is aimed to summarize the knowledge about avidity of selected autoantibodies in certain autoimmune diseases. The avidity of various autoantibodies differs under distinct clinical situations. High-, moderate or low-avidity may be found in biological fluids in patients with autoimmune diseases.The avidity maturation associated with progression from low to high values typical for antibodies against exogenous antigens is not always uniform in autoimmune diseases; therefore, the avidity of each autoantibody should be judged individually. Some studies promise the possible benefit of avidity examination for the refinement of diagnosis and prediction of selected autoimmune diseases.Key words: affinity - anti-citrullinated protein antibodies - anti-glomerular basement membrane antibodies - anti-glutamate decarboxylase antibodies - anti-insulin antibodies - autoantibodies - avidity - onconeuronal antibodies.

Avidity of antiphospholipid antibodies - our current knowledge.

Antiphospholipid antibodies (APL), which represent serum markers of the antiphospholipid syndrome, comprise an extremely heterogeneous group of autoantibodies directed against various phospholipids and protein cofactors. The heterogeneity of APL includes not only their antigen-binding site specificity but also their avidity. The aim of this study was to summarize the current knowledge about commonly-used procedures for the avidity determination with a special interest in the antiphospholipid antibodies and to evaluate the clinical significance of APL avidity determination. The common techniques in clinical laboratories for avidity determination utilize the ELISAs in the presence of various chaotropic agents. The findings of clinical studies suggest that the high avidity APL are associated with thrombosis and antiphospholipid syndrom (APS). The determination of APL avidity might be a complementary laboratory marker applicable in the classification of APS.

Avidity of anti-neurocytoskeletal antibodies in cerebrospinal fluid and serum.

Antibodies have different avidities that can be evaluated using modified enzyme-linked immunosorbent assay (ELISA) techniques. We determined levels and avidities of antibodies to light (NFL) and medium (NFM) subunits of neurofilaments and tau protein in serum and cerebrospinal fluid (CSF) from 26 patients and anti-tau antibody levels and their avidities in 20 multiple sclerosis (MS) patients and 20 age- and sex-matched controls. Each sample was analyzed using both standard ELISA and also using a similar ELISA protocol with the addition of urea. The avidities of anti-neurocytoskeletal antibodies were higher in the CSF than those in serum (anti-NFL, p < 0.0001; anti-tau, p < 0.01; anti-NFM, n.s.). There was no relationship between avidities in serum and CSF for individual anti-neurocytoskeletal antibodies. We did not observe the relationship among the avidities of various anti-neurocytoskeletal antibodies. The avidities of anti-tau antibodies in the CSF were significantly higher in the MS patients than those in the controls (p < 0.0001). The study demonstrates the differences in avidities of CSF or serum neurocytoskeletal antibodies measured as the urea resistance by ELISA method. Avidity determination of anti-neurocytoskeletal antibodies could contribute to the evaluation of the immunological status of patients.

European Psychiatric Association guidance on the conflicts of interest.

Conflict of interest (COI) is a set of circumstances that creates a risk that professional judgments or actions regarding a primary interest will be unduly influenced and compromised by a secondary interest. It might arise in clinical practice, research, and education, and might include individuals and institutions. Primary interests include the pursuit of well-being of patients, ensuring the independence of medical education, and protecting the objectivity and integrity of medical research. Secondary interests might involve financial interests, pursuit of recognition and professional career advancement. COI might result from the multiple roles of physicians in patient care, research, administration, provision of expert opinion and policy advice, and consultancy to commercial organizations. The purpose of the COI policy is to protect the interests of the patients, strengthen the integrity of the profession, and preserve public trust in medicine and psychiatry. The aim of the guidance is to eventually prevent these conflicts from arising rather than remediate them ex post. It is desirable to identify factors that might lead to their occurrence, offer a framework for their recognition and assessment, introduce the principles and standards of their disclosure, and provide recommendations for their transparent resolution.

Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis.

BACKGROUND: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). METHODS: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. RESULTS: Serum levels of anti-NFL were higher in ALS patients than in controls (P < 0.005). Serum anti-NFL antibodies and intrathecal anti-NFM antibodies were related to patient disability (serum anti-NFL: P < 0.05; intrathecal anti-NFM: P < 0.05). Anti-NFL levels were significantly correlated with anti-NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti-NFL and anti-NFM antibodies significantly correlated between serum and CSF in the ALS group (anti-NFL: P < 0.0001; anti-NFM: P < 0.001) and in the control group (anti-NFL: P < 0.05; anti-NFM: P < 0.05). CONCLUSIONS: Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.

Relationship between ALS and the degree of cognitive impairment, markers of neurodegeneration and predictors for poor outcome. A prospective study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease affecting motor neurons and may be associated with impaired cognition. Reliable prognostic factors for ALS patients are still missing. METHODS: We prospectively included 67 patients, 42 women and 25 men, with clinically defined ALS. The disease severity was assessed and the patients underwent SPECT, lumbar puncture with determination of tau, hyperphosporylated tau (p-tau) and beta-amyloid and a detailed neuropsychological assessment using a standardized test battery. In patients who died, a detailed neuropathologic evaluation was performed. RESULTS: The mean survival duration was 26.8 months. The delay between the first signs and confirmation of the diagnosis was 12.75 months. Cognitive impairment did not have an impact on the evolution of the disease. There was no correlation between neuropsychological and SPECT findings. Higher age at onset, more pronounced handicap and elevated beta-amyloid in the CSF were associated with shorter survival times. In brain tissue from nine of the deceased patients with ALS and dementia, all showed signs of comorbidity, six had hallmarks of frontotemporal lobar degeneration (FTLD) and three showed Alzheimer disease pathology. Brain tissues form 11 deceased ALS patients who did not show signs of dementia, had only changes compatible with a diagnosis of motor neuron disease. CONCLUSION: In our prospective study, age, disease severity and CSF beta-amyloid levels taken together were a risk factor suggesting shorter survival times. Dementia is relatively frequent in ALS and may be a consequence of either FTLD or result from co-existing Alzheimer disease.

Synergy of serum and cerebrospinal fluid antibodies against axonal cytoskeletal proteins in patients with different neurological diseases.

Autoantibodies against different axonal cytoskeletal proteins [the light (NFL) and medium (NFM) subunit of neurofilament and tubulin (TUB)] in serum and cerebrospinal fluid may be generated in response to the release of cytoskeleton from damaged neurons. We studied the relationships among these autoantibodies. Paired cerebrospinal fluid (CSF) and serum samples were obtained from 47 multiple sclerosis (MS) patients, 14 patients with neurodegenerative diseases, 21 patients with various neurological diseases and 16 normal control subjects. Levels of antibodies against NFL, NFM and TUB were related to each other in CSF in all groups, whereas close association of anti-cytoskeletal antibodies in serum was found in the MS group only. A concordant spectrum of anti-cytoskeletal antibodies is present in serum of MS patients, unlike in other neurological patients. The synergy between the spectrum of anti-cytoskeletal antibodies in serum and CSF might be one of the immunological features typical for the MS patients.

Cerebrospinal fluid antibodies to tubulin are elevated in the patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The aim of this study was to compare the levels of anti-tubulin antibodies (anti-TU) in cerebrospinal fluid (CSF) and serum using bovine tubulin as the antigen in one enzyme-linked immunosorbent assay (ELISA) method (anti-TUb antibodies) and a synthetic neuron-specific octapeptide of tubulin in a second ELISA method (anti-TUs antibodies). METHODS: Paired CSF and serum samples were obtained from 34 multiple sclerosis (MS) patients, 13 patients with various other neurological diseases (control diseases) and 17 normal control patients (CN). RESULTS: CSF levels of anti-TUs and anti-TUb antibodies were significantly lower in the CN group when compared to those in the MS group. On the contrary, serum levels of anti-TU antibodies did not differ among groups. The intrathecal synthesis of anti-TUs antibodies in comparison with anti-TUb was significantly increased in all groups. Significant correlations between anti-TUb and anti-TUs antibodies were observed in the CSF of all three groups. However, with regard to serum, a similar relationship was only found in the MS group. CONCLUSIONS: The estimation of anti-TU in CSF can contribute to the overall assessment of axonal damage; on the contrary serum anti-tubulin antibodies were not useful for differential purposes in MS. The antibodies to the neuron-specific portion of tubulin seemed to be synthesised predominantly intrathecally.

Advanced oxidation protein products in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a risk factor of hypertension, coronary artery disease and stroke. OSA is also considered a cause of accelerated atherogenesis. Advanced oxidation protein products (AOPP) are among the biochemical indicators of higher risk of atherogenesis as an independent risk factor for coronary artery disease. 20 men suffering from OSA were examined using night polygraphy, the AOPP were determined from their morning blood samples. The mean AOPP concentration in the patients group was 91.8 (SD=42.3) micromol/l, in the control group 76.2 (SD=35.3) pmol/l, the difference was not significant. The AOPP were found correlated with the AHI (apnoe/hypopnoe index) (R=0.485, P=0.030). The results support the hypothesis that OSA increases the oxidative stress and atherogenesis.

Antibodies against light neurofilaments in multiple sclerosis patients.

OBJECTIVES: Axonal damage in multiple sclerosis (MS) may be reflected by antibodies against axon-specific proteins - the light subunit of neurofilaments (NFL). MATERIALS AND METHODS: The serum and cerebrospinal fluid obtained from 58 MS patients, 24 normal controls (CN), 49 control patients with miscellaneous diseases (CD) and 31 patients with neurodegenerative disorders (CDEG) were tested for both immunoglobulin G and M antibodies against NFL, using an ELISA. RESULTS: Intrathecal IgG antibodies to NFL were elevated in MS patients compared with that in CD patients (P = 0.001) and were not related to clinical variables. No differences in IgM anti-NFL levels were found between the MS and CN/CD groups. IgM to NFL was higher in the CDEG group than in either the CD group or even the MS group (P < 0.0005). CONCLUSIONS - Intrathecal IgM or IgG antibodies to NFL are not useful surrogate markers for axonal damage or disease subtypes in MS.

Pregnancy-associated plasma protein-A in patients with cerebrovascular diseases--a pilot study.

Pregnancy-associated plasma protein-A (PAPP-A) was described as a novel marker of acute coronary syndrome. The aim of our study was to investigate how serum pregnancy-associated plasma protein-A (PAPP-A) levels change in patients with ischaemic stroke and intracerebral haemorrhage and to evaluate if PAPP-A might be a marker not only of myocardial infarction but also a useful parameter in cerebrovascular disorders. 43 patients with acute cerebrovascular events were divided into 3 groups--patients with ischaemic stroke (n=16), patients with intracranial haemorrhage (n=10) and patients with both ischaemic stroke and coronary artery disease (n=17). The control group consisted of 12 subjects. PAPP-A was measured by TRACE (Time Resolved Amplified Cryptate Emission) technology. PAPP-A levels in patients with intracranial haemorrhage and those with both ischaemic stroke and coronary artery disease were increased in comparison with the control group (p<0.005, p<0.01, respectively) as well as with patients with ischaemic stroke only (p<0.01, p<0.05, respectively). A positive correlation between PAPP-A and total cholesterol in patients with both ischaemic stroke and coronary artery disease (r=0.497, p<0.05) was observed. Serum PAPP-A levels in all studied patients correlated positively with serum creatinine (r=0.395, p<0.05). PAPP-A levels are increased in patients with intracranial haemorrhage and in the patients whose ischaemic stroke is associated with coronary artery disease. The atherosclerotic process may contribute to increased serum PAPP-A levels. PAPP-A may be a marker of increased risk of atherothrombotic events in general.

Oxidative stress and inflammation in pregnancy.

Pregnancy is a period when increased oxidative stress can be expected. We have focused especially on oxidative stress and inflammation in the period of pregnancy, when prenatal screening is usually performed. We determined advanced oxidation protein products (AOPPs), C-reactive protein (CRP) and anticardiolipin antibodies (ACA) IgG and IgM levels in the serum of 86 pregnant women in the 1st trimester and 102 pregnant women in the 2nd trimester. AOPP levels in the maternal serum of pregnant women were significantly higher in the 1st and 2nd trimesters than they were in that of non-pregnant women (p<0.0001, p<0.001, respectively). Maternal serum CRP levels, too, were increased compared with those in non-pregnant women (1st and 2nd trimester versus non-pregnant women p<0.05, p<0.005, respectively). Just as with AOPPs and CRP, the ACA IgG levels in pregnant women were significantly higher in both trimesters than they were in non-pregnant women (1st and 2nd trimesters versus non-pregnant women p<0.05, p<0.001, respectively). Maternal serum CRP levels correlated positively with AOPPs in the 2nd trimester (r = 0.504, p<0.05). The increased levels of AOPPs, CRP and ACA IgG in the 1st and 2nd trimesters may reflect a maternal response to inflammatory and oxidative stress in pregnant women.

Hyperlipoproteinemia impairs endothelium-dependent vasodilation.

Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol>4.1 mmol/l or triglycerides>2.5 mmol/l or taking any of lipid lowering drugs)--94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals--30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13+/-3.07 vs. 5.41+/-3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68+/-0.22 vs. 0.58+/-0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77+/-9.54 vs. 56.49+/-7.80 U/l; p=0.015), malondialdehyde (0.89+/-0.09 vs. 0.73+/-0.08 micromol/l; p=0.010) and nitrites/nitrates (20.42+/-4.88 vs. 16.37+/-4.44 micromol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.

Oxidative stress, inflammation and autoimmune reaction in type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) is associated with oxidative stress, elevation of inflammatory markers and other mechanisms, which may contribute to accelerated atherosclerosis. The aim of the study was to determine prominent factors of these pathogenic processes in patients with DM, to examine their relationship in serum, and to find out the differences between DM1 and DM2. Advanced oxidation protein products (AOPP), C-reactive protein (CRP), pregnancy-associated plasma protein-A (PAPP-A), anticardiolipin antibodies (ACA) and anti-beta2-glycoprotein-1 antibodies (anti-beta2-GPI) were determined in 27 patients with DM1, 27 patients with DM2 and 23 healthy subjects. AOPP, CRP and anti-beta2-GPI were significantly elevated in DM2 in comparison with healthy subjects (p<0.01, p<0.0001, p<0.0001, respectively). In DM1, anti-beta2-GPI were elevated (p<0.0001) as well, but there was no increase of either AOPP or CRP. There was no difference in PAPP-A levels in DM1 or DM2 and healthy subjects. In DM 1, AOPP correlate significantly with anti-beta2-GPI (r = 0.68, p<0.05). In DM2, there is a significant correlation between anti-beta2-GPI and PAPP-A (r=0.45, p<0.05). Oxidative stress and inflammation are more expressed in DM2 and they are partly related. In DM1, oxidative stress seems to be in closer link to autoimmune reaction than to inflammation.

Increased levels of pregnancy-associated plasma protein A are associated with mortality in hemodialysis patients: preliminary results.

Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic indicator of acute coronary syndrome. This protein is elevated in hemodialysis (HD) patients and is closely related to inflammation and oxidative stress. The aim of our pilot study was to find out whether PAPP-A is related to mortality in HD patients. 40 HD patients in a stable clinical state (20 men and 20 women, mean age 69 +/- 12 years) were enrolled in the study and followed up for 20 months. PAPP-A was assessed immunochemically (TRACE method) in serum samples (before the HD session) at the beginning of the observation period. During the follow-up, 22 patients died, 15 of them due to cardiovascular events. PAPP-A levels were significantly higher in the patients who died, compared to living HD patients: 26.8 (21.6-36.8) vs. 20 (14.9-26.6) mU/l, p = 0.034. PAPP-A could also be a new prognostic marker in hemodialysis patients, probably due to its close association with cardiovascular risk. More extensive studies are required to confirm this hypothesis.

Relationship of pregnancy-associated plasma protein-a to renal function and dialysis modalities.

BACKGROUND: The aim of the study was to determine pregnancy-associated plasma protein-A (PAPP-A), which was recently described as a new marker of cardiovascular events, in patients with chronic renal insufficiency/failure and to find out its relationship to renal function and to prominent markers of oxidative stress (advanced oxidation protein products--AOPP) and inflammation (C-reactive protein--CRP). METHODS: The studied group consisted of 36 chronic hemodialysis patients (HD), 10 patients treated with continuous ambulatory peritoneal dialysis (CAPD) and 38 patients with chronic renal insufficiency (CHRI) not yet dialyzed. PAPP-A was measured by Time Resolved Amplified Cryptate Emission technology. Determination of AOPP is based on a spectrophotometric method. RESULTS: PAPP-A levels are statistically significantly elevated in the both groups of dialyzed patients in comparison with healthy subjects (27.0 +/- 16.5 mIU/l in HD and 14.07 +/- 6.73 mIU/l in CAPD vs. 8.22 +/- 2.7 mIU/l in the control group, p < 0.0001 and p < 0.001, respectively, p < 0.05 HD vs. CAPD). The mean serum PAPP-A levels in the CHRI patients not yet dialyzed were not significantly higher in comparison with the control group (9.72 +/-4.44 vs. 8.22 +/- 2.7 mIU/l, n.s.). In the CHRI not dialyzed patients, we found a significant positive correlation between serum creatinine and PAPP-A levels (r = 0.68, p < 0.05). In comparison with controls, AOPP and CRP levels were significantly higher in HD patients [AOPP 155.0 +/- 37.9 micromol/l, p < 0.0001 vs. controls, CRP 10.0 (4.6- 26.9) mg/l (median, interquartile range), p < 0.0001 vs. controls], CAPD patients [AOPP 118.5 +/- 25.8 micromol/l, p < 0.0001 vs. controls, CRP 7.7 (2.0-18.8) mg/l, p < 0.01 vs. controls] and AOPP levels in chronic renal failure patients not yet dialyzed (98.5 +/- 43.24 micromol/l, p < 0.01 vs. controls). The correlations between PAPP-A and AOPP (r = 0.49, p < 0.05) and PAPP-A and CRP (r = 0.48, p < 0.05) serum concentration were statistically significant in HD patients. In CAPD patients, neither a correlation between PAPP-A and AOPP nor a correlation between PAPP-A and CRP were found. CONCLUSION: We can conclude that serum PAPP-A levels sensitively reflect the changes in renal function, depend on dialysis modality, and may represent a novel marker associated with inflammation and oxidative stress in chronic renal failure patients.

Pregnancy-associated plasma protein A during hemodialysis with polyamide and diacetate cellulosic membranes.

Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic factor of acute coronary syndrome in the general population. It is elevated in hemodialysis (HD) patients and at baseline, it was shown to be related to inflammation and oxidative stress. The aim of the study was to examine the relationship of PAPP-A and oxidative stress and inflammatory markers to HD treatment. Studied parameters were determined in 10 chronic HD patients treated with low flux polyamide (1st session) and diacetate cellulosic membranes (2nd session) at the beginning, after 15 minutes and at the end of the dialysis session. TRACE method (Time Resolved Amplified Cryptate Emission) was used for PAPP-A assessment. Results were evaluated with ANOVA. PAPP-A levels did not depend on the type of HD membrane but changed significantly with the time of the HD session. They increased significantly from the beginning of HD to 15 min and then decreased to the end of the HD session - p<0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for polyamide membrane and p=0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for diacetate cellulosic membrane. Changes in other parameters and differences between membranes were only minimal. We can conclude that PAPP-A as a marker of cardiovascular damage shows significant changes during the HD session. Its initial increase might be ascribed to its release from complexes or storage. During dialysis, it might be destroyed or cleaved and removed as free fragments. Its levels both before and after the HD session are higher than in healthy subjects.

Markers of inflammation in preeclampsia.

Advanced oxidation protein products (AOPP) represent terminal products of proteins exposure to free radicals. The aim of this study was to estimate the serum AOPP levels in preeclamptic patients together with ultrasensitive C-reactive protein and anticardiolipin antibodies (ACA) IgG and IgM. 21 women in the third trimester of pregnancy were included in the study--10 women with preeclampsia and 11 women with normal outcome of pregnancy. AOPP levels in preeclampsia were higher than those in normal pregnant women in the third trimester, but not statistically significantly. The comparison with AOPP levels in non-pregnant women has shown a significant increase (P<0.0001). CRP in preeclampsia was significantly increased in comparison with third trimester levels in normal pregnancy (P<0.001) as well as with non-pregnant women (P<0.0001). In preeclampsia, the ACA IgG levels were even significantly lower than in normal pregnant women in the same gestation age, but significantly higher than in non-pregnant women (P<0.001). No difference was found in ACA IgM in preeclampsia and normal third trimester pregnancy and non-pregnant women. A statistically significant negative correlation was found between AOPP and ACA IgG (r= - 0.708, P<0.05). The results indicate enhanced oxidative and inflammatory reaction of maternal organism to pregnancy, which is more pronounced in preeclampsia than in uncomplicated pregnancy.

[Levels of advanced oxidation protein products (AOPP) in the first trimester of pregnancy]. / Hladiny produktu pokrocilé oxidace proteinu (AOPP) v prvním trimestru tehotenství.

Advanced oxidation protein products (AOPP) may be sensitive biomarkers for protein damage mediated by reactive oxygen species. AOPP were measured in the serum of 41 pregnant women in the 8th-12th week of pregnancy. Parameters of prenatal screening in the first trimester (pregnancy-associated plasma protein A--PAPP-A and free beta human chorionic gonadotrophin--free beta HCG) and anticardiolipin antibodies (ACA) IgG and IgM were determined as well. A group of healthy blood donors--women and men was used for comparison. AOPP were determined spectrophotometrically according to Witko-Sarsat [24] (absorbance at 340 nm) and were expressed in chloramine units (mumol/l). Other analytes were determined by immunoanalytic methods. AOPP levels in pregnant women in the first trimester are significantly higher in comparison with blood donors--women (89.46 +/- 33.38 mumol/l vs 57.34 +/- 16.31 mumol/l, p < 0.0001) but there is no statistically significant difference between pregnant women and blood donors--men (89.46 +/- 33.38 mumol/l vs 78.60 +/- 44.01 mumol/l). AOPP level does not correlate either with the age of pregnant women or with the parameters of prenatal screening and ACA IgG and IgM. Higher levels of AOPP in the serum of pregnant women in comparison with women--blood donors may reflect an increase of oxidative stress in pregnancy.