OTHER ARTICLES PUBLISHED IN THIS SERIES Dying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clinical and Experimental Immunology 2015, 179: 5-10. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16
SummaryRecently we reported the first known incidence of antibodies possessing catalytic sialidase activity (sialidase abzymes) in the serum of patients with multiple myeloma and systemic lupus erythematosus (SLE). These antibodies desialylate biomolecules, such as glycoproteins, gangliosides and red blood cells. Desialylation of dying cells was demonstrated to facilitate apoptotic cell clearance. In this study we assessed the possibility to facilitate dying cell clearance with the use of F(ab)2 fragments of sialidase abzymes. Two sources of sialidase abzymes were used: (i) those isolated from sera of patients with SLE after preliminary screening of a cohort of patients for sialidase activity; and (ii) by creating an induced sialidase abzyme through immunization of a rabbit with synthetic hapten consisting of a non-hydrolysable analogue of sialidase reaction conjugated with bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). Antibodies were purified by ammonium sulphate precipitation, protein-G affinity chromatography and size exclusion-high performance liquid chromatography (HPLC-SEC). Effect of desialylation on efferocytosis was studied using human polymorphonuclear leucocytes (PMN), both viable and aged, as prey, and human monocyte-derived macrophages (MoMa). Treatment of apoptotic and viable prey with both disease-associated (purified from blood serum of SLE patients) and immunization-induced (obtained by immunization of rabbits) sialidase abzymes, its F(ab)2 fragment and bacterial neuraminidase (as positive control) have significantly enhanced the clearance of prey by macrophages. We conclude that sialidase abzyme can serve as a protective agent in autoimmune patients and that artificial abzymes may be of potential therapeutic value.
Sialation of cell surface is known to be tightly connected with tumorigenicity, invasiveness, metastatic potential and clearance of aged cells, while sialation of immunoglobulin G (IgG) molecules determines their anti-inflammatory properties. Recently, we have found for the first time IgG-antibodies possessing sialidase-like activity (sialylic abzyme) in blood serum of multiple myeloma and systemic lupus erythematosis patients. This abzyme was detected in a pool of IgGs purified by a typical procedure including immunoglobulin's precipitation with ammonium sulfate and following chromatography on protein G-Sepharose column. Here we describe a novel matrix for affinity purification of sialylic abzyme that is based on using bovine submandibular gland mucin conjugated to Sepharose matrix (mucin-Sepharose). This matrix preferentially binds sialidase-like IgGs from a pool of sialidase-active fraction of proteins precipitated with 50% ammonium sulfate from blood serum of the systemic lupus erythematosis patients. That allowed us to develop a new scheme of double-step chromatography purification of sialidase-like IgGs from human blood serum.
The presence of several diff erent autoantibodies (auto-AT) at the same time is a specifi c peculiarity of the "autoantibody profi le" of SLE (systemic lupus erythematosus). It is known that the induction of auto-AT formation involves both nonspecifi c and antigen-specifi c immunoregulatory disorders. In apoptosis, the primary changes in the cell membrane composition or/ and the excretion of intracellular compounds into the intercellular milieu lead to an infl ammatory reaction.The purpose of the study was to highlight the connection between apoptosis and secondary necrosis of granulocytes and mononuclear (lymphocytes and monocytes) with infl ammation activity in patients with SLE to improve diagnosis and basic therapy effi cacy. In patients with SLE, secondary necrosis of granulocytes was 3.4 times higher compared to healthy control. Moreover, the level of apoptotic monocytes was 1.87 times higher, and secondary necrosis of monocytes was 5.58 times higher than healthy control. The secondary necrosis of lymphocytes was higher 9.0 times than in the case of healthy control. The usage of Apolect technology in patients with SLE allows diff erentiating various cell types of immunological infl ammation with the analysis of the degree of apoptosis and secondary necrosis of immunocompetent cells (granulocytes, monocytes, lymphocytes) to determine the aggressiveness of cytostatic therapy and predict the development of complications of this disease.
Machine learning is used to develop predictive models to diagnose different diseases, particularly kidney transplant survival prediction. The paper used the collected dataset of patients’ individual parameters to predict the critical risk factors associated with early graft rejection. Our study shows the high pairwise correlation between a massive subset of the parameters listed in the dataset. Hence the proper feature selection is needed to increase the quality of a prediction model. Several methods are used for feature selection, and results are summarized using hard voting. Modeling the onset of critical events for the elements of a particular set is made based on the Kapplan-Meier method. Four novel ensembles of machine learning models are built on selected features for the classification task. Proposed stacking allows obtaining an accuracy, sensitivity, and specifity of more than 0.9. Further research will include the development of a two-stage predictor.
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