Snezana Zivancevic-Simonovic

Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis

Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1—interferon gamma (IFN-γ); Th2—interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9—interleukin 9 (IL-9); and Th17—interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

Murine monoclonal antibody 26 raised against tetanus toxoid cross-reacts with beta2-glycoprotein I: its characteristics and role in molecular mimicry.

Problem  Studies on experimental antiphospholipid syndrome (APS) models proved that molecular mimicry between plasma protein β2‐glycoprotein I (β2GPI) and structure within micro‐organisms or their products, might be a cause for experimental APS. Considering the heterogeneity of polyclonal antiphospholipid antibodies (aPLs), it is important to define the precise characteristics of pathogenic aPLs. To avoid the influence of polyclonality and to further analyse the connection between molecular mimicry and APS, we produced monoclonal antibodies (MAbs) against tetanus toxoid (TTd) and tested their reactivity against β2GPI.

Idiotypic and Anti‐Idiotypic Antibodies Produced in Immune Response to Bacteria Lactobacillus acidophyllus

Lactobacilli are nonpathogenic gram‐positive inhabitants of the normal human intestine known for their health‐promoting effects. In our earlier work, it is shown that human monoclonal antibody isolated from sera of a patient with Waldenstrom macroglobulinaemia possess innate antibody characteristics and binds to lactic acid bacteria. According to the immune network model, immunization with this bacteria could induce the perturbations in immune system that might result in production of anti‐Lactobacillus antibodies, human monoclonal antibody like (Ab1) and anti‐idiotypic antibody (Ab2). In this study, BALB/c mice were immunized with two doses of bacteria Lactobacillus acidophilus in complete and incomplete Freunds adjuvant and phosphate‐buffered saline (PBS), respectively. Seven days after the last immunization, sera from immunized mice were collected and the presence of Lactobacillus‐specific Ab1 and Ab2 were determined by ELISAs. In the sera of immunized mice, antibodies specific to bacteria Lactobacillus acidophilus were shown. The concentration of Lactobacillus‐specific antibodies was higher in the sera of hyperimmunized mice (mice immunized with 1 mg of IgM DJ) than in sera of mice immunized with 100 times lower doses of immunogen (0.01 mg per doses). Moreover, Ab1 and Ab2 antibodies were detected in the sera of Lactobacillus‐hyperimmunized mice. In this study, we have shown the idiotypic network interactions in mice immunized with bacteria Lactobacillus acidophilus.

Fatigue in Patients with Autoimmune Thyroid Diseases

Abstract Fatigue is a common feature in a wide variety of chronic inflammatory and autoimmune diseases, but fatigue in autoimmune thyroid disease (AITD) has not been investigated so far. The aim of this study was to examine fatigue in patients with AITD and to analyse the correlation between fatigue and the serum concentrations of thyroid antibodies, thyroid function and depression. This cross-sectional clinical study included 62 patients with increased concentrations of thyroperoxidase antibodies (TPOAbs) as confirmation of AITD and 52 healthy individuals who were negative for thyroid antibodies; all controls were euthyroid. Thyroid antibodies, free thyroxine and thyroid-stimulating hormone were measured in the sera of all subjects. The Fatigue Severity Scale was used to measure the severity of fatigue; the level of depression was measured by the Beck Depression Inventory. Eight (12.9%) patients had evident fatigue, 7 (11.3%) patients had fatigue limit values, and 47 (75.8%) patients had no fatigue. The frequency of fatigue was highly significant and almost three times higher in the AITD patients compared to the control group, in which only 2 (3.8%) patients had evident fatigue. The majority of patients with fatigue had normal thyroid function, and only one (1.6%) patient had overt hypothyroidism. Seven (11.3%) patients had both fatigue and depression, whereas one (1.6%) patient had fatigue without depression. We did not find significant correlations between fatigue and the concentrations of thyroid antibodies, but we found statistically significant correlations between fatigue and depression in AITD patients.

ORIGINAL ARTICLE: Murine Monoclonal Antibody 26 Raised Against Tetanus Toxoid Cross-Reacts with β2-Glycoprotein I: Its Characteristics and Role in Molecular Mimicry: MAB26 PROPERTIES AND ITS ROLE IN MOLECULAR MIMICRY

Problem  Studies on experimental antiphospholipid syndrome (APS) models proved that molecular mimicry between plasma protein β2‐glycoprotein I (β2GPI) and structure within micro‐organisms or their products, might be a cause for experimental APS. Considering the heterogeneity of polyclonal antiphospholipid antibodies (aPLs), it is important to define the precise characteristics of pathogenic aPLs. To avoid the influence of polyclonality and to further analyse the connection between molecular mimicry and APS, we produced monoclonal antibodies (MAbs) against tetanus toxoid (TTd) and tested their reactivity against β2GPI.