A detailed examination of the antibody prevalence and characteristics of anti-ESA antibodies

Abstract

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.

Measurement of Anti-Erythropoiesis-Stimulating Agent IgG4 Antibody as an Indicator of Antibody-Mediated Pure Red Cell Aplasia

“…We have previously shown that there is a strong statistical correlation between the anti-ESA antibody concentration and patients with amPRCA (3) and the presence of anti-ESA IgG4 and anti-ESA neutralizing antibody activity in amPRCA patients (9). Here, we have demonstrated a strong correlation between the anti-ESA IgG4 antibody concentration and patients with am-PRCA.…”

“…Therefore, after confirmation of amPRCA, it is recommended that treatment with any erythropoietin-based ESA should be immediately discontinued (8). An anti-ESA IgG1 antibody response appears in some antibody-positive non-PRCA patients but is also present with the detection of IgG4 in patients who develop amPRCA (3,9). Although the IgG1 response is considered to precede the IgG4 response, the switch is driven by the repeated and prolonged exposure to the ESA.…”

“…The long-term administration of biological therapeutics such as beta interferon (IFN-␤) 1b to multiple sclerosis patients (11) and factor VIII to hemophilia A patients (12) results in the development of IgG4 ADA. The development of anti-ESA IgG4 antibodies against erythropoietin-based ESAs is best studied in the nephrology patient population and has been shown to be coincident with amPRCA (3,6,9).…”

A Randomized, Masked, Placebo-Controlled Study of Darbepoetin Alfa in Preterm Infants

“…Anti-ESA IgM reactivity to glycosylated therapeutic proteins has been previously demonstrated to ESAs in other patient populations. 30 At present, there are no published reports of neonates receiving more than single doses of Darbe, and further study is required in a larger population of ELBW infants to identify side effects specific to neonates. This study was not powered to identify differences in the low incidence of any side effects, specifically ROP, a preterm morbidity that has been linked to early use of Epo.…”

T-cell assays confirm immunogenicity of tungsten-induced erythropoietin aggregates associated with pure red cell aplasia

“…This finding is consistent with previously published reports of mixed IgG subclass patterns found in antibody-mediated PRCA patients. 2,14,15 Tungsten, used in heat-resistant drilling pins for glass syringe manufacturing was identified as the most likely root cause for aggregation in prefilled syringes of this lot. 13 Polytungstates leaching from prefilled syringes may elicit protein aggregation, dependent on the pH of the solution, the tungsten species, and concentration.…”