Jana Švarcová

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).

Patients with Alzheimer disease have elevated intrathecal synthesis of antibodies against tau protein and heavy neurofilament

The role of humoral immunity related to neuron- and disease-specific cytoskeletal proteins patients with Alzheimer disease (AD) is unknown. We measured antibodies against tau protein, light and heavy (NFH) neurofilaments using ELISA in 80 paired serum and cerebrospinal fluid (CSF) samples from patients with AD, with other dementias (OD), with neuro-inflammatory diseases (IC) and 25 controls (NC). We estimated intrathecal synthesis according to the formula (CSF/serum anti-neurocytoskeletal IgG)/(CSF/serum total IgG). AD patients had significantly higher intrathecal anti-tau and anti-NFH antibodies than the other groups. These innovative findings may hint at specific alterations in humoral anti-neurocytoskeletal immunity and selectivity in AD, which could have diagnostic and immunotherapeutic implications.

Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus.

Receptor for advanced glycation end-products (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= - 0.602, p<0.002 and r= - 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

Biochemical oxidative stress-related markers in patients with obstructive sleep apnea

Summary Background Obstructive sleep apnea (OSA) is a condition contributing to oxidative stress. The aim of this study was to ascertain if there is any connection between OSA and novel oxidative stress-related markers. Matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), high sensitive C-reactive protein (hsCRP), pregnancy-associated plasma protein-A (PAPP-A), soluble receptors for advanced glycation end-products (sRAGE), zinc (Zn) and copper (Cu) were measured. Further biochemical markers were evaluated. Material/Methods Fifty-one men suspected for OSA indicated for night polygraphy were included. Apnea/hypopnea index (AHI), oxygen desaturation index (ODI), mean blood hemoglobin oxygen saturation (SpO2) and time of blood hemoglobin oxygen saturation below 90% (SpO2 <90%) were measured. Morning venous blood samples were taken. Results For body mass index (BMI) we found strong positive correlation with levels of Cu, MMP-9, hsCRP and fibrinogen, and negative correlation with sRAGE. Concerning ventilation parameters, we found positive correlation of ODI and SpO2 <90% with markers MMP-9 and hsCRP. sRAGE level correlated with AHI and ODI negatively. SpO2 correlated negatively with Cu, MMP-9, hsCRP and fibrinogen. There was no correlation between ventilation parameters and markers MMP-2, PAPP-A and Zn. Compared to severity of OSA, there was significant difference in levels of hsCRP and Cu between patients with AHI ≤5 and AHI ≥30 independent of BMI. Conclusions MMP-9, hsCRP, sRAGE and Cu seem to be strong predictors of oxidative stress in OSA patients. The strong correlation between oxidative stress-related markers and OSA is elucidated by connection of these to BMI, which is probably a primary condition of oxidative stress, but OSA is an additive condition.

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.

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).

Serum and cerebrospinal fluid heavy neurofilaments and antibodies against them in early multiple sclerosis

Heavy neurofilaments (NFH) released from neurons during axonal injury induce a humoral immune response. We measured CSF and serum levels of NFH proteins and anti-NFH IgG antibodies in 19 patients with clinically isolated syndrome (CIS) converting to multiple sclerosis, in 20 stable CIS patients, 23 patients with multiple sclerosis (MS) and 32 control subjects using ELISA. CSF and intrathecal levels and CSF/serum ratios of anti-NFH antibodies were increased in the CIS patients early developing MS while NFH protein concentrations were similar among the groups. Changes associated with NFH are more pronounced for antibodies than for protein itself and may aid in prediction of CIS patients.

Low maternal serum matrix metalloproteinase (MMP)-2 concentrations are associated with preterm labor and fetal inflammatory response.

Abstract Objectives: To assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation. Methods: Maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. Results: Maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. Conclusion: Our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA.

Association of pregnancy-associated plasma protein A polymorphism with preeclampsia — A pilot study

OBJECTIVES The aim of the study was to investigate genetic and biochemical background of PAPP-A (pregnancy-associated plasma protein A) in patients with risk pregnancies. DESIGN AND METHODS Five PAPP-A gene polymorphisms and PAPP-A maternal serum levels were studied together in 165 women in third trimester pregnancies complicated with threatening preterm labor (n=98), preeclampsia (n=35), intrauterine growth restriction (n=34) and ICP (intrahepatic cholestasis of pregnancy) (n=15). 114 healthy pregnant women served as controls. RESULTS Preeclamptic patients had significantly higher frequency of TT genotype of Cys327Cys polymorphism compared to controls (p<0.01). Patients with ICP had increased serum levels of PAPP-A compared to controls and correlation analysis showed significant relationship between PAPP-A and CRP (C-reactive protein) in the patients with intrauterine growth restriction (r=0.49, p=0.007). CONCLUSION Our study indicates the association of TT genotype of Cys327Cys polymorphism of the PAPP-A gene with preeclampsia. However, further study with larger groups of preeclamptic patients is needed to confirm our results.