@misc{Padjas_Agnieszka_Antibodies_2008,
 author={Padjas, Agnieszka},
 address={Kraków},
 howpublished={online},
 year={2008},
 school={Wydział Lekarski},
 language={pol},
 abstract={A role of elevated homocysteine (Hcy) levels in autoimmune disorders and their complications remains unclear. One of the recently discovered mechanisms underlying harmful effects of Hcy is the generation of Nε-homocysteinylated proteins (Nε-Hcy-proteins) such as Nε-homocysteinylated-albumin (Nε-Hcyalbumin) and Nε-homocysteinylated-hemoglobin (Nε-Hcy-hemoglobin), which may stimulate a specific humoral immune system response. Anti-Nε-Hcy-protein IgG antibodies have been detected in subjects with ischemic heart disease, with endstage renal disease and after stroke. The level of anti-Nε-Hcy protein antibodies in the patients was significantly higher compared with age- and sex-matched controls. It is still not known whether in autoimmunologic diseases, in which increased plasma levels of Hcy are commonly observed, there is a tendency to produce anti- Nε-Hcy protein antibodies. The aims of the study were: 1. to assess the occurrence of anti-Nε-Hcy-albumin and -hemoglobin antibodies in patients with the most common systemic auotoimmunologic disorders, i.e. systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), 2. to identify factors that determine these antibodies in autoimmunologic diseases, 3. to assess variability of levels of anti-Nε- Hcy-protein antibodies in patients with autoimunologic disorders. One hundred and thirty patients (108 women, 22},
 abstract={men) with autoimmunologic diseases, in a stable phase of the disease (median age, 43 years) and 66 matched for age and sex, apparently healthy individuals were enrolled to this case-control study. Blood samples were collected after a 14-hour overnight fast. Total plasma Hcy (tHcy) levels were determined by high-performance liquid chromatography. Serum folic acid and vitamin B12 levels were measured using a Immunolite analyzer. Antinuclear antibody (ANA) were assessed with indirect immunofluorescency, anticardiolipin (ACL) and anti-β2 glycoprotein i (anti-β2GPI) antibodies levels were measured by immunofluorescency. Serum levels of IgG antibodies against Nε-Hcyalbumin and Nε-Hcy-hemoglobin were determined using an in-house enzyme-linked immunosorbent assay. The methylenotetrahydrofolate reductase (MTHFR) C677T polymorphism was determined by the polymerase chain reaction. The highest percentage of the patients were individuals with SLE (68.5%) (mean disease duration, 7 years; score in SLEDAI scale, 0 and 5) and with APS (43.1%). Three patients with systemic sclerosis, 7 subjects with mixed connective tissue disease and 6 patients with dermatomyositis were also enrolled to the study. In the SLE group 34.8% of patients met criteria for APS and 55.4% of the subjects with APS, fulfilled the criteria for SLE. Patients had lower hemoglobin, HDL-cholesterol and serum c},
 abstract={omplement (C4) concentration and higher lymphocyte count, triglycerides and C-reactive protein (CRP) concentration than healthy subjects. In the patient group there were also found higher levels of tHcy (median IQR; 11.4 [8.9-13.4] vs 9.1 [8.2-10.8] μmol/l, p<0.0001) and lower folic acid (5.46 [4.28-6.94] vs 9.26 [6.88-11.1 ng/mL], p<0.0001) and vitamin B12 concentrations (60 [217-308] vs 313.5 [245-414] pg/L, p=0.004) compared with controls. a prevalence of the 677TT genotype in autoimmunologic patients was 12.3%. In the patient group levels of anti-Nε-Hcyalbumin (0.325 [0.236-0.536] vs 0.199 [0.167-0.254], p<0.0001) and Nε-Hcyhemoglobin antibodies (0.433 [0.332-0.646] vs 0.291 [0.24-0.362]; p<0.0001) were significantly higher as compared to the control group. As expected, there were significant associations between tHcy and levels of anti-Nε-Hcy-albumin (r=0.67, p<0.0001) and -hemoglobin antibodies (r=0.66, p<0.0001). Weak inverse correlations were also observed between anti-Nε-Hcy-albumin and -hemoglobin antibodies, and folic acid concentrations (r=-0.18, p=0.04 and r=-0.17, p=0.05, respectively). Moreover, there were positive associations between anti-Nε-Hcyprotein antibodies levels and CRP concentration (r=0.8, p<0.0001, for both antibodies). No associations between demographic features and the antibodies were found. Carriers of the TT genotype had signif},
 abstract={icantly higher levels of anti-Nε-Hcyalbumin and -hemoglobin antibodies compared to subjects with CC and CT genotypes. In SLE patients (women, 86.5%, mean disease duration, 7 years), weak positive correlations between anti-Nε-Hcy-albumin and -hemoglobin antibodies and ANA titers (r=0.26, p=0.01; r=0.28, p=0.008, respectively) were found. Patients with antidouble strain DNA (anti-dsDNA) antibodies had higher levels of anti-Nε-Hcyalbumin (0.375 [0.268-0.653] vs 0.317 [0.216-0.49], p=0.04) and -hemoglobin antibodies (0.488 [0.372-0.777] vs 0.424 [0.32-0.611], p=0.02), compared to those without anti-dsDNA anibodies. There were also correlations between anti-Nε-Hcyalbumin and -hemoglobin antibodies and ACL IgG levels (r=0.57, p<0.0001 i r=0.5, p<0.0001, respectively) and anti-GPI IgG concentrations (r=0.38, p=0.0003 i r=0.36, p=0.0004, respectively). In SLE patients there were also positive correlations between the analyzed antibodies and CRP concentrations. Associations between anti-Nε-Hcy-protein antibodies and both the SLE patients' age and disease duration were also noted. Patients with lupus nephritis had higher levels of anti-Nε- Hcy-albumin (0.375 [0.268-0.653] vs 0.3 [0.216-0.435], p=0.01) and -hemoglobin antibodies (0.493 [0.372-0.770] vs 0.404 [0.315-0.543], p=0.005) than those without kidney disease. There were no associations between the treatment used a},
 abstract={nd the analyzed antibodies. In the APS patients (women, 75%, mean disease duration, 7 years) positive correlations between anti-Nε-Hcy-albumin and -hemoglobin antibodies and ACL IgG levels (r=0.75, p<0.0001 i r=0.73, p<0.0001) and concentrations of anti-β2GPI antibodies (r=0.46, p=0.004 i r=0.47, p=0.003) were found. Higher levels of anti-Nε-Hcy-albumin (0.481 [0.344-0.669] vs 0.363 [0.237-0.540], p=0.048) and -hemoglobin antibodies (0.591 [0.441-0.791] vs 0.468 [0.341-0.667], p=0.046) were found in subjects with lupus anticoagulant (LA) compared to the remaining APS patients. In APS patients there were also positive correlations between anti-Nε-Hcy-protein antibodies and CRP concentrations. No associations were found between anti-Nε-Hcy-proteins antibodies and clinical manifestations, treatment and the age of the APS patients. There were correlations only between tHcy concentrations and levels of both anti- Nε-Hcy-albumin (r=0.61, p<0.0001) and -hemoglobin antibodies (r=0.59, p<0.0001) in healthy subjects. Similarly to the results in the patients, control subjects with the TT genotype had significantly higher levels of anti-Nε-Hcy-albumin and -hemoglobin antibodies compared to those with CC- and CT-genotype. By the linear regression analysis, performed in a whole group of 130 patients, tHcy and CRP concentrations were independent predictors of level of anti-N},
 abstract={ε-Hcyprotein antibodies. In the SLE patients, tHcy, CRP and disease duration were independently associated with levels of anti-Nε-Hcy-protein antibodies. Total Hcy, CRP and ACL IgG concentrations were the independent predictors of anti-Nε-Hcyprotein antibodies levels in subjects with APS. In 39 randomly selected patients with autoimmunologic diseases levels of anti-Nε- Hcy-hemoglobin antibodies and the percentage of seropositivity were similar when repeated after 9 months. There were significant differences between anti-Nε-Hcyalbumin antibodies levels in the patients, however the percentage of seropositivity after 9 months was similar. In conclusion, stable patients with systemic autoimmunologic diseases have significantly higher levels of anti-Nε-Hcy-albumin and -hemoglobin IgG antibodies than healthy individuals, which are associated with increased tHcy levels. In SLE patients production of anti-Nε-Hcy-albumin and -hemoglobin antibodies is associated with ANA titers and depends on the inflammatory status and disease duration. In APS patients, production of anti-Nε-Hcy-protein antibodies is related to the ACL IgG level, the presence of LA and, similarly to SLE, they depend on the inflammatory status. High levels of anti-Nε-Hcy-protein antibodies are stable over time. The current study suggests that hyperhomocysteinemia associated with autoimmunologic diseas},
 abstract={es results in the generation of specific, so far unknown, antibodies, which may help explain the associations between Hcy metabolism and development of autoimmune disorders However, further prospective studies are needed to elucidate the role of anti-Nε-Hcy-protein antibodies in the cardiovascular complications in autoimmunologic diseases.},
 title={Antibodies to homocysteinylated proteins in selected patients with autoimmunologic diseases},
 type={Praca doktorska},
 keywords={SLE, APS, homocysteine, N-homocysteinylated proteins, antibodies to N-homocysteinylated proteins},
}