CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS

Biological preparations (BP) obtained by gene engineering possess a special characteristic called immunogenicity, i.e. propensity of biological drugs to induce an undesired immune response associated with arising anti-drug antibodies. These antibodies can change BP pharmacokinetics and pharmacodynam...

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Autores principales:	V. D. Nazarov, S. V. Lapin, V. A. Dobronravov, K. A. Smirnov, D. A. Mayer, T. O. Muzhetskaya, A. A. Totolian
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2018
Materias:	erythropoietin anemia immunogenicity antibodies Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/404653d3121049a18d24b7924dea3d80
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spelling	oai:doaj.org-article:404653d3121049a18d24b7924dea3d802021-11-18T08:03:47ZCIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS1563-06252313-741X10.15789/1563-0625-2018-1-129-134https://doaj.org/article/404653d3121049a18d24b7924dea3d802018-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1440https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XBiological preparations (BP) obtained by gene engineering possess a special characteristic called immunogenicity, i.e. propensity of biological drugs to induce an undesired immune response associated with arising anti-drug antibodies. These antibodies can change BP pharmacokinetics and pharmacodynamics, and therapeutical efficacy. A significant proportion of hemodialysis patients with end-stage renal disease treated by recombinant erythropoietin (rEPO) have clinical features of resistance to such therapy. The aim of the study was to investigate whether anti-rEPO antibodies are associated with hemoglobin concentrations (Hb) and red blood cells counts (RBC) in hemodialysis patients, receiving long-term rEPO therapy. This research was performed at the Research Institute of Nephrology at the First St. Petersburg I.Pavlov State Medical University. Thirty-seven hemodialysis patients (pts) with end-stage renal disease and anemia treated with different rEPO formulations were included into the study. The patients were further divided into two groups: those with diminished and normal clinical response to rEPO therapy (DCR, n = 21 vs NCR group, n = 16, respectively). To determine threshold levels of antibodies to rEPO-beta (Roche, Switzerland) we tested blood serum samples of 35 healthy blood donors who never received rEPO in the past. Concentration of antibodies was measured by means of dot-blot method. The threshold antibody concentrations were defined by measurement of anti-rEPO concentrations in 2-fold stepwise dilutions (1:10 to 1:200) of blood sera from 35 healthy donors .The threshold value for rEPO-binding antibodies was 20.27 µg/ml (95 CI%±0.43). Antibodies to rEPO were found in 54 % of serum samples in the patients. Anti-rEPO antibodies concentrations correlated with mean values of hemoglobin and erythrocyte counts over a period of 12-months for the entire group of hemodialysis patients (r = -0.368, p = 0.025 and r = -0.336, p = 0.042 respectively). Concentration of anti-rEPO antibodies, and the mean weekly rEPO dose were significantly higher in DCR group, compared to NCR group (p = 0.0019). In conclusion, higher levels of anti-rEPO binding antibodies seem to be associated with decreased therapeutic response to the clinically applied rEPO formulations.V. D. NazarovS. V. LapinV. A. DobronravovK. A. SmirnovD. A. MayerT. O. MuzhetskayaA. A. TotolianSPb RAACIarticleerythropoietinanemiaimmunogenicityantibodiesImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 20, Iss 1, Pp 129-134 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	erythropoietin anemia immunogenicity antibodies Immunologic diseases. Allergy RC581-607
spellingShingle	erythropoietin anemia immunogenicity antibodies Immunologic diseases. Allergy RC581-607 V. D. Nazarov S. V. Lapin V. A. Dobronravov K. A. Smirnov D. A. Mayer T. O. Muzhetskaya A. A. Totolian CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
description	Biological preparations (BP) obtained by gene engineering possess a special characteristic called immunogenicity, i.e. propensity of biological drugs to induce an undesired immune response associated with arising anti-drug antibodies. These antibodies can change BP pharmacokinetics and pharmacodynamics, and therapeutical efficacy. A significant proportion of hemodialysis patients with end-stage renal disease treated by recombinant erythropoietin (rEPO) have clinical features of resistance to such therapy. The aim of the study was to investigate whether anti-rEPO antibodies are associated with hemoglobin concentrations (Hb) and red blood cells counts (RBC) in hemodialysis patients, receiving long-term rEPO therapy. This research was performed at the Research Institute of Nephrology at the First St. Petersburg I.Pavlov State Medical University. Thirty-seven hemodialysis patients (pts) with end-stage renal disease and anemia treated with different rEPO formulations were included into the study. The patients were further divided into two groups: those with diminished and normal clinical response to rEPO therapy (DCR, n = 21 vs NCR group, n = 16, respectively). To determine threshold levels of antibodies to rEPO-beta (Roche, Switzerland) we tested blood serum samples of 35 healthy blood donors who never received rEPO in the past. Concentration of antibodies was measured by means of dot-blot method. The threshold antibody concentrations were defined by measurement of anti-rEPO concentrations in 2-fold stepwise dilutions (1:10 to 1:200) of blood sera from 35 healthy donors .The threshold value for rEPO-binding antibodies was 20.27 µg/ml (95 CI%±0.43). Antibodies to rEPO were found in 54 % of serum samples in the patients. Anti-rEPO antibodies concentrations correlated with mean values of hemoglobin and erythrocyte counts over a period of 12-months for the entire group of hemodialysis patients (r = -0.368, p = 0.025 and r = -0.336, p = 0.042 respectively). Concentration of anti-rEPO antibodies, and the mean weekly rEPO dose were significantly higher in DCR group, compared to NCR group (p = 0.0019). In conclusion, higher levels of anti-rEPO binding antibodies seem to be associated with decreased therapeutic response to the clinically applied rEPO formulations.
format	article
author	V. D. Nazarov S. V. Lapin V. A. Dobronravov K. A. Smirnov D. A. Mayer T. O. Muzhetskaya A. A. Totolian
author_facet	V. D. Nazarov S. V. Lapin V. A. Dobronravov K. A. Smirnov D. A. Mayer T. O. Muzhetskaya A. A. Totolian
author_sort	V. D. Nazarov
title	CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
title_short	CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
title_full	CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
title_fullStr	CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
title_full_unstemmed	CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS
title_sort	circulating antibodies to erythropoietin are associated with lower efficacy of recombinant epoetin treatment in patients undergoing haemodialysis
publisher	SPb RAACI
publishDate	2018
url	https://doaj.org/article/404653d3121049a18d24b7924dea3d80
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CIRCULATING ANTIBODIES TO ERYTHROPOIETIN ARE ASSOCIATED WITH LOWER EFFICACY OF RECOMBINANT EPOETIN TREATMENT IN PATIENTS UNDERGOING HAEMODIALYSIS

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