BACKGROUND: The antibody characteristics in erythropoiesis-stimulating agent (ESA)-treated patients who develop antibody-mediated pure red cell aplasia (PRCA; amPRCA) can be described as high-affinity, neutralizing anti-ESA antibodies with a mixed immunoglobulin G (IgG) subclass. The characteristics of an early-onset anti-ESA antibody response are not well documented, especially in the months prior to the development of amPRCA. Therefore, a detailed characterization of anti-ESA antibodies was performed in patients in both clinical studies and in a post-market setting. Both baseline and post-dose samples were tested and antibody-positive samples were characterized. Antibody characteristics such as concentration, isotype and specificity were evaluated in subjects with non-neutralizing anti-ESA antibodies and subjects that developed neutralizing anti-ESA antibodies associated with amPRCA. METHODS: Serum samples were analyzed for the presence of anti-ESA antibodies, using a validated surface plasmon resonance (SPR)-based immunoassay or SPRIA. RESULTS: Among the clinical studies, pre-existing non-neutralizing anti-ESA antibodies were found in 6% of the subjects from clinical studies in nephrology, oncology and congestive heart failure (CHF). After ESA treatment, 2.3% of the subjects developed binding, non-neutralizing antibodies with 0.1% confirmed as having an IgG isotype and were specific to the ESA protein. IgM antibodies were detected at baseline and post-ESA treatment and reported to be specific to the glycosylation of the ESA. No clinical study subjects progressed to amPRCA. In contrast, anti-ESA antibody-positive subjects from the post-market setting with a confirmed IgG subclass were specific to the ESA protein. Subjects that had progressed to amPRCA were noted to have high antibody concentrations with neutralizing activity and a diverse IgG subtype. CONCLUSIONS: A low prevalence of non-neutralizing anti-ESA IgM specific to glycosylation on the ESA and IgG1 antibodies specific to the ESA protein was detected across all clinical patient populations. Patients with amPRCA were noted to have high IgG antibody concentrations, neutralizing antibodies and the presence of anti-ESA IgG4 antibodies.
BACKGROUND: The antibody characteristics in erythropoiesis-stimulating agent (ESA)-treated patients who develop antibody-mediated pure red cell aplasia (PRCA; amPRCA) can be described as high-affinity, neutralizing anti-ESA antibodies with a mixed immunoglobulin G (IgG) subclass. The characteristics of an early-onset anti-ESA antibody response are not well documented, especially in the months prior to the development of amPRCA. Therefore, a detailed characterization of anti-ESA antibodies was performed in patients in both clinical studies and in a post-market setting. Both baseline and post-dose samples were tested and antibody-positive samples were characterized. Antibody characteristics such as concentration, isotype and specificity were evaluated in subjects with non-neutralizing anti-ESA antibodies and subjects that developed neutralizing anti-ESA antibodies associated with amPRCA. METHODS: Serum samples were analyzed for the presence of anti-ESA antibodies, using a validated surface plasmon resonance (SPR)-based immunoassay or SPRIA. RESULTS: Among the clinical studies, pre-existing non-neutralizing anti-ESA antibodies were found in 6% of the subjects from clinical studies in nephrology, oncology and congestive heart failure (CHF). After ESA treatment, 2.3% of the subjects developed binding, non-neutralizing antibodies with 0.1% confirmed as having an IgG isotype and were specific to the ESA protein. IgM antibodies were detected at baseline and post-ESA treatment and reported to be specific to the glycosylation of the ESA. No clinical study subjects progressed to amPRCA. In contrast, anti-ESA antibody-positive subjects from the post-market setting with a confirmed IgG subclass were specific to the ESA protein. Subjects that had progressed to amPRCA were noted to have high antibody concentrations with neutralizing activity and a diverse IgG subtype. CONCLUSIONS: A low prevalence of non-neutralizing anti-ESA IgM specific to glycosylation on the ESA and IgG1 antibodies specific to the ESA protein was detected across all clinical patient populations. Patients with amPRCA were noted to have high IgG antibody concentrations, neutralizing antibodies and the presence of anti-ESA IgG4 antibodies.
Authors: Tina Rubic-Schneider; Masataka Kuwana; Brigitte Christen; Manuela Aßenmacher; Otmar Hainzl; Frank Zimmermann; Robert Fischer; Vera Koppenburg; Salah-Dine Chibout; Timothy M Wright; Andreas Seidl; Michael Kammüller Journal: Blood Adv Date: 2017-02-09
Authors: Robin K Ohls; Robert D Christensen; Beena D Kamath-Rayne; Adam Rosenberg; Susan E Wiedmeier; Mahshid Roohi; Conra Backstrom Lacy; Diane K Lambert; Jill J Burnett; Barbara Pruckler; Ron Schrader; Jean R Lowe Journal: Pediatrics Date: 2013-06-17 Impact factor: 7.124
Authors: Dorina van der Mey; Michael Gerisch; Natalia A Jungmann; Andreas Kaiser; Kenichi Yoshikawa; Simone Schulz; Martin Radtke; Silvia Lentini Journal: Basic Clin Pharmacol Toxicol Date: 2020-12-12 Impact factor: 4.080
Authors: Gérard London; Johannes Mann; David Goldsmith; Christian Combe; Frank Dellanna; Philippe Zaoui; Nadja Hoebel; Andriy Krendyukov; Karen MacDonald; Ivo Abraham Journal: Clin Nephrol Date: 2018-01 Impact factor: 0.975