Complement activation-related pseudo allergy of PEGylated products: Safety aspects, models, the role of anti-PEG antibodies, and ways to overcome | ||||
| Journal of advanced Biomedical and Pharmaceutical Sciences | ||||
| Article 3, Volume 5, Issue 2, April 2022, Page 79-87 PDF (425.63 K) | ||||
| Document Type: Review Articles | ||||
| DOI: 10.21608/jabps.2022.113694.1146 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Mahmoud Mohamed   1; Nehal Elsadek2; Sherif Emam 3; hamdy Abdelkader 4; Usama Farghaly 5; Hatem Sarhan5
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| 1Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima, Japan. | ||||
| 2Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima, Japan | ||||
| 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. Institute of Biomedical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima, Japan. | ||||
| 4Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Department of Pharmaceutics, College of Pharmacy, King Khaled University, Abha, Saudi Arabia. | ||||
| 5Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt | ||||
| Abstract | ||||
| PEGylated products were reported to suffer accelerated blood clearance (ABC) phenomenon upon injection into the same animal twice. The PEG moiety is recognized by the immune system and induces antibodies production. Anti-PEG antibodies can bind PEGylated products and form immune complexes. This interaction activates the complement system and attaches to the preformed immune complex. The larger immune complexes were captured by the liver to be eliminated. Complement activation is considered vital for the ABC phenomenon. As well, complement activation can induce allergic reactions upon injection of several approved pharmaceutical ingredients or drug delivery systems resulting in the so-called “complement activation related pseudo allergy”. CARPA accompanied with an injection of the approved PEGylated products is common. In this review, we tried to discover the correlation between the ABC phenomenon and CARPA. Complement activation resembles the meeting point of the two phenomena. Based on our investigations, we can conclude and confirm that the anti-PEG antibodies play a pivotal role in the induction of most CARPA symptoms associated with PEGylated products. Unfortunately, naturally occurring anti-PEG antibodies have a widespread between population which may carry potential CARPA upon consumption of PEGylated products. In conclusion, the expression of CARPA manifestations for PEGylated products is controlled by several factors like the pre-existence of anti-PEG antibodies, anti-PEG antibodies titer, and antigen-antibody ratio. | ||||
| Keywords | ||||
| PEG; anti-PEG antibodies; ABC phenomenon; complement activation; CARPA | ||||
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