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Where disease pathogenesis meets protein formulation: renal deposition of immunoglobulin aggregates

Published in European Journal of Pharmaceutics and Biopharmaceutics. 2006, vol. 62, no. 2, p. 121-130
Abstract Aggregation is one of the important issues encountered during the development of immunoglobulin-based drugs. The aim of the current review is to discuss the causes and consequences of immunoglobulin aggregation as well as the relevance of immunoglobulin aggregation to disease pathogenesis. Extracellular deposition of immunoglobulins, either monoclonal light chains or intact polyclonal antibodies, induces renal failure in various nephropathies. The aggregates can present fibrillar or amorphous structures. In this review, factors known to influence protein aggregation, such as the primary structure of the protein, local environment and glycosylation are assessed, as well as the subsequent altered clearance, fibril formation and toxicity. The role of the protein local environment is emphasized. Even if the local environment causes only minor perturbations in the protein structure, these perturbations might be sufficient to trigger aggregate formation. This fact underlines the importance of choosing appropriate formulations for protein drugs. If the formulation provides a slightly destabilizing environment to the protein, the long-term stability of the drug may be compromised by aggregate formation.
Keywords ImmunoglobulinAggregationDiseaseFormulationTherapeutic proteinsAmyloid
PMID: 16221544
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DEMEULE, Barthelemy, GURNY, Robert, ARVINTE, Tudor. Where disease pathogenesis meets protein formulation: renal deposition of immunoglobulin aggregates. In: European Journal of Pharmaceutics and Biopharmaceutics, 2006, vol. 62, n° 2, p. 121-130. https://archive-ouverte.unige.ch/unige:84824

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Deposited on : 2016-06-29

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