Suppression of autoreactive T and B lymphocytes by anti-annexin A1 antibody in a humanized NSG murine model of systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic inflammatory disease which involves multiple organs. Self-specific B and T cells play a main role in the pathogenesis of lupus and have been defined as a logical target for selective therapy. The protein annexin A1 (ANX A1) is a modulator of the immune system involving many cell types. An abnormal expression of ANX A1 was found on activated B and T cells during autoimmunity, suggesting its importance as a potential therapeutic target. We hypothesize that it may be possible to down-regulate the activity of autoreactive T and B cells from lupus patients in a humanized immunodeficient mouse model by treating them with an antibody against ANX A1. When cultured in the presence of anti-ANX A1, peripheral blood mononuclear cells (PBMC) from lupus patients showed a decreased number of immunoglobulin (Ig)G anti-dsDNA antibody-secreting plasma cells, decreased T cell proliferation and expression of activation markers and increased B and T cell apoptosis. We employed a humanized model of SLE by transferring PBMCs from lupus patients to immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. The humanized animals presented autoantibodies, proteinuria and immunoglobulin deposition in the renal glomeruli. Treatment of these NOD-SCID mice with an anti-ANX A1 antibody prevented appearance of anti-DNA antibodies and proteinuria, while the phosphate-buffered saline (PBS)-injected animals had high levels after the transfer. The treatment reduced the levels of autoantibodies to several autoantigens, lupus-associated cytokines and disease symptoms.

Th17 cells in Bulgarian children with chronic obstructive lung diseases

Introduction and objectives: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. Patients and methods: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3 + CD4 + CD161 + CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. Results: The BA patients had a significantly higher percentage of Th17 (12.40 ± 1.16%) compared to the CF children (7.64 ± 0.87%, p = 0.0035) and healthy (7.25 ± 0.45%, p = 0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p = 0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p = 0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08 ± 3.09% vs. 6.25 ± 2.42%, p = 0.294). Conclusions: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies

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Serum trefoil factor 3 predicts disease activity in patients with ulcerative colitis.

OBJECTIVE: In this study, we aimed to evaluate the role of serum trefoil factor 3 (TFF3) as a biomarker of disease activity in patients with inflammatory bowel disease (IBD) and to compare TFF3 values with those of fecal calprotectin (FC). PATIENTS AND METHODS: 128 patients with IBD were divided into four groups: 1) active ulcerative colitis (UC); 2) quiescent UC; 3) active Crohn's disease (CD); 4) quiescent CD. The serum levels of TFF3 and FC levels were assessed in all patients and 16 controls. RESULTS: Patients with active UC had higher TFF3 levels than those with quiescent UC (p<0.001), those with active (p<0.001) or quiescent CD (p<0.001) and controls (p <0.001). We found a correlation between TFF3 and FC values in patients with active (r = 0.478, p = 0.006) and quiescent UC (r=0.528, p=0.002). TFF3 levels correlated with endoscopic activity in UC (evaluated by UC Endoscopic Index of Severity - UCEIS) (r=0.662, p<0.001). CONCLUSIONS: Serum TFF3 is able to identify patients with active UC. It could be used as a marker to predict disease activity in patients with UC.

Th17 cells in Bulgarian children with chronic obstructive lung diseases.

INTRODUCTION AND OBJECTIVES: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. PATIENTS AND METHODS: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3+CD4+CD161+CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. RESULTS: The BA patients had a significantly higher percentage of Th17 (12.40±1.16%) compared to the CF children (7.64±0.87%, p=0.0035) and healthy (7.25±0.45%, p=0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p=0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p=0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08±3.09% vs. 6.25±2.42%, p=0.294). CONCLUSIONS: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies.

[Calcium desorption from the cornea while using complex-forming substances]. / Desorbtsiia kal'tsiia iz rogovoi obolochki glaza pri ispol'zovanii kompleksoobrazovatelei.

The time course of calcium desorption from the eye cornea and the efficacy of the use of complex-forming substances during desorption were examined. Experiments with labeled calcium showed an active absorption of the ions by the normal cornea thereby making it turbid. The removal of labeled calcium from an isolated eye and from corneal pieces while using a combination of complex-forming substances and diffusion facilitating-papain was accompanied by the lowering of tissue turbidity. Application of such combinations might eliminate, in some cases, the necessity of surgical operations on the cornea.