Magdalena Sobieska

Indicators of immune activation in major depression

Immune-inflammatory markers and their correlations were examined in patients with major depression. Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), transferrin receptor (TfR), C-reactive protein (CRP), and alpha 1-acid glycoprotein (AGP), as well as the microheterogeneity of AGP, were measured in 49 major depressed patients during an acute phase of the illness and compared with concentrations in 15 normal control subjects. Plasma concentrations of IL-6, sIL-6, sIL-2R, TfR, CRP, and AGP were significantly higher in major depressed patients than in healthy control subjects. Patients with higher values of AGP microheterogeneity coefficient (AGP-RC > 1.5) had significantly higher concentrations of AGP, IL-6, and TfR. The correlations between cytokines and acute phase proteins studied point to a significant role of elevated IL-6 secretion in the induction of Type I AGP microheterogeneity changes that are characteristic of some inflammatory conditions.

Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression

This study was performed on 32 patients with refractory depression in whom lithium was added to antidepressant treatment in order to potentiate the therapeutic effect, and in 20 healthy controls. Plasma concentration of three acute-phase proteins (APPs): C-reactive protein, alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) as well as microheterogeneity of AGP and ACT were measured, before and after 4 weeks of lithium addition to antidepressants. Before Li addition, all patients studied had elevated values of APPs, which suggested the existence of immunological activation. A significant decrease in plasma levels of all APPs and the decrease of glycosylation values of AGP and ACT was observed after Li potentiation. A favorable clinical effect of lithium potentiation after 4 weeks was found in 24 patients (75%). Nonresponders to Li potentiation differed from responsers by their immunological indices prior to Li addition. They had higher values of reactivity coefficients, which means more inflammatory patterns.

Concentration and microheterogeneity glycophorms of alpha-1-acid glycoprotein in major depressive disorder

Serum alpha-1-acid glycoprotein (AGP) concentration and its microheterogeneity were measured in 46 patients with major depressive disorder and in 20 age- and sex-matched controls. The changes in major microheterogeneity of AGP were expressed as reactivity coefficient (AGP-RC). Also measured were the levels of C-reactive protein as well as leukocyte, neutrophil and monocyte counts. The results obtained showed that two thirds of the depressed patients studied, exhibited some immune disturbances during acute episode: first with a high AGP and high AGP-RC, and secondly with a low AGP-RC. The patients with the highest AGP-RC and higher AGP values had a longer duration of the illness and of the last depressive episode, a higher resistance to previous treatments, and a higher monocyte count. The character of the changes in the microheterogeneity of AGP bears some similarity to those observed in other diseases with immunological disturbances.

Serum brain-derived neurotrophic factor in euthymic bipolar patients on prophylactic lithium therapy.

Aim: The aim of the study was to evaluate serum brain-derived neurotrophic factor (BDNF) levels in a group of euthymic bipolar patients on long-term prophylactic lithium treatment and to delineate putative relationships between lithium efficacy and BDNF concentrations. Methods: 141 euthymic bipolar patients (51 male, 90 female) on long-term lithium treatment were studied. Three categories of prophylactic lithium response were delineated: excellent lithium responders (ER; 30 patients), partial lithium responders (PR; 61 patients) and lithium nonresponders (NR; 50 patients). The control group consisted of 75 age- and gender-matched healthy subjects. Results: The lithium-treated patients as a whole group had lower BDNF levels compared to the healthy controls. However, after breaking down the patients into ER, PR and NR, it appeared that only NR had significantly lower BDNF levels compared with the healthy control subjects. No association between the age of the patients, duration of bipolar illness, and serum lithium and BDNF levels was found. Conclusion: The results point to a relationship between lithium prophylactic efficacy and plasma BDNF levels in euthymic bipolar patients where lithium NR had reduced BDNF levels. These findings suggest that serum BDNF is associated with lithium efficacy in bipolar disorder.

Still's disease in children and adults: A distinct pattern of acute-phase proteins

Crossed affinoimmunoelectrophoresis with Con A as a ligand was used to examine the microheterogeneity of α1-acid glycoprotein (AGP) and α1-antichymotrypsin (ACT) in sera of patients with child-onset and adult-onset Stills disease. The reactivity of both proteins was increased in sera of adults and decreased in sera of children with active disease, when compared with normal values. We also found statistically significant differences in serum concentration of ACT and ferritin in both diseases. This result suggests different pathogenic mechanisms of Stills disease in children and adults. Serum concentration of ferritin and ACT could be of value as a combined marker for the adult, but not the juvenile form of Stills disease.

Changes of acute phase proteins glycosylation profile as a possible prognostic marker in myocardial infarction

In 24 consecutive patients with myocardial infarction, the concentrations of C-reactive protein, alpha 1-acid glycoprotein and alpha 1-antichymotrypsin, as well as acid alpha 1-glycoprotein and alpha 1-antichymotrypsin glycosylation profiles were estimated. Blood samples were taken at admission, after 4, 8, 12 and 24 h, on 2, 3, 6, 9, and 12 days of hospitalization. All studied patients were divided into 2 groups: 12 patients without clinical or radiological symptoms of acute heart failure and 12 patients with acute heart failure. The results of all investigations were tested statistically to appraise significance of differences between the two investigated groups. At admission, as well as after 6 and 12 h, C-reactive protein concentration was significantly higher in patients who developed heart failure. Similarly, the glycosylation profile of alpha 1-antichymotrypsin, reported as reactivity coefficient, was of good prognostic value from the first time-point on. Development of acute cardiac failure seemed to correlate more with the magnitude of inflammatory reaction (measured by changes in acute phase proteins) than with enzymatically estimated infarct size.

Microheterogeneity of alpha 1 acid glycoprotein in rheumatoid arthritis: dependent on disease duration?

The microheterogeneity of alpha 1 acid glycoprotein (AGP) was studied using affinity immunoelectrophoresis with concanavalin A (Con A) in serum samples of 43 patients with early rheumatoid arthritis (RA) without clinical features of intercurrent infection. The results were expressed as reactivity coefficients. Disease activity was measured by clinical (Lansburys joint index, Mallya-Mace activity score) and laboratory (erythrocyte sedimentation rate, levels of soluble interleukin-2 receptor, C reactive protein, and AGP) indices. In contrast with previous reports, suggesting a decrease in AGP-Con A reactivity in patients with RA, high values of AGP reactivity coefficients were found in patients with disease of short duration, which were similar to those found in patients with acute bacterial infections. Conversely, normal or decreased values of AGP reactivity coefficients were found in patients with disease of longer duration. Regression analysis showed a significant relation between AGP reactivity coefficients and disease duration (multiplicative model). No other indices examined were significantly related to disease duration. These results, taken together with previous findings suggesting that cytokines control the glycosylation of acute phase proteins, indicate that differences in the microheterogeneity of AGP in early and longstanding RA reflect differences in cytokine action at different stages of the disease.

Obesity, physical fitness, and inflammatory markers in Polish children

Background The relationship between obesity, physical fitness, and inflammation was analyzed in a Polish population aged 12 to 18 years. Material/Methods Body mass index measurements and Eurofit physical fitness tests were undertaken to assess the adiposity and physical fitness status, respectively, of subjects. Serum samples were collected to measure standard inflammatory markers, including interleukin 6; and the acute-phase proteins alpha1-acid glycoprotein and alpha1-antichymotrypsin. In addition, the glycosylation profiles of alpha1-acid glycoprotein and alpha1-antichymotrypsin were analyzed to further evaluate immune statuses. Results The physical fitness of individuals was negatively influenced by obesity. Obese subjects were characterized by an abnormal immune balance, including increased levels of alpha1-acid glycoprotein, as well as alpha1-antichymotrypsin, and altered glycosylation profiles indicative of an underlying inflammatory condition. Older age, male sex, and a large body mass index appeared to correlate with poor physical fitness scores and a disturbed immune status. Conclusions Impaired physical fitness is indicative for non-compensated overweight and affects mainly males aged 15 to 18 years. Female subjects seemed to cope better with increased body mass.

Achieving motor development milestones at the age of three months may determine, but does not guarantee, proper further development.

Proper motor performance at 3rd month is necessary for further motor development. The paper aims to demonstrate the reliability, sensitivity, and predictive value of an original motor performance assessment tool in comparison with the neurological assessment at 3, 6, and 9 months. Children (n = 123), born at term without pre- or perinatal complications, born at term with pre- or perinatal complications, or born preterm, were assessed at the age of 3, 6, and 9 months, by a neurologist and a physiotherapist. The physiotherapist evaluated 15 qualitative features typical for the age of 3 months in the prone and supine positions. The final neurological assessment determined the degree of developmental disorder. Neurological and global physiotherapeutic assessments showed a statistically significant correlation. Qualitative assessment results were very good in healthy children and decreased with worsening neurological diagnoses. Children diagnosed with cerebral palsy did not show proper qualitative features of 3 months when analyzed at 3, 6, and 9 months. Children with delayed motor development revealed minor qualitative performance impairments as early as 3 months but improved with age. Qualitative assessment at 3 months not only facilitates diagnosis of major developmental disorders but is also a good predictor of delayed motor development in children.

Different capabilities of monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis to induce glycosylation alterations of acute phase proteins in vitro.

The effect of conditioned medium on the biosynthesis and glycosylation profile of acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied. Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with active rheumatoid arthritis (RA), five patients with active systemic lupus erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin, alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(-) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+) from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability to induce changes in the biosynthesis and glycosylation of acute phase proteins. Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1-antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes isolated from patients with active SLE and active RA have different capabilities of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation of monocytes from patients with SLE leads to the full induction of its capabilities to change acute phase proteins, whereas the activation of monocytes from patients with RA has no additive effects; and (c) interleukin 6 seems to be a major cytokine involved in the regulation of the glycosylation pattern of acute phase proteins.