Predicting the likelihood of late complications after administration of PLA-based drug products

Introduction. Poly-L-lactic acid (PLA) fillers correct skin volume loss by stimulating fibroblasts to synthesize collagen. Tissues around the PLA injection site accumulate CD68+ macrophages and CD90+ fibroblasts. They also increase the levels of TGF-β1 and tissue inhibitor of metalloproteinase 1 (TIMP1), which promote the deposition of collagen I and III. One of the serious complications after the introduction of poly-L-lactic acid (PLA) fillers is granulomatous inflammation. Genetic testing is of great interest in terms of predicting both the effectiveness of cosmetic procedures and their safety.

Aim. To determine the genetic predisposition to unwanted fibrosis and the likelihood of developing granulomatous inflammation (foreign body reaction) after the introduction of PLA-based products.

Materials and methods. The pilot study involved 54 female patients who underwent vector lifting procedures, a PLA-based drug, and genetic testing. Buccal epithelium served as the material for the molecular genetic study. PCR was performed using a Rotor Gene Q amplifier (Qiagen, Germany).

Results. The study clearly identified patterns of granulomatous inflammation development in patients with IL-4 and IL-13 gene polymorphism. Comparison of the two groups showed that markers rs2243250_IL-4 and rs20541_IL-13 have statistically significant differences (p < 0.05), indicating their potential association with complications. Correlation analysis confirmed the presence of a moderate positive relationship between complications in the form of a delayed granulomatous reaction to the introduction of a PLA-based filler and the rs2243250_IL-4_TT gene (Rm = 0.480, p = 0.020*), which emphasizes its significance in this sample. Univariate analysis showed that the rs2243250_IL-4_TT gene, indicating a high mutation, significantly increases the risk of an unfavorable outcome (OR = 32.008, p = 0.011*).

Conclusions. Findings show that the presence of polymorphism and substitution in two alleles in the rs2243250_IL-4_TT gene variant significantly increases the risk of adverse outcomes.

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