Evaluation of dynamic control of continuous capture with periodic counter-current chromatography under feedstock variations.

Multi-column periodic counter-current chromatography is a promising technology for continuous antibody capture. However, dynamic changes due to disturbances and drifts pose some potential risks for continuous processes during long-term operation. In this study, a model-based approach was used to describe the changes in breakthrough curves with feedstock variations in target proteins and impurities. The performances of continuous capture of three-column periodic counter-current chromatography under ΔUV dynamic control were systematically evaluated with modeling to assess the risks under different feedstock variations. As the concentration of target protein decreased rapidly, the protein might not breakthrough from the first column, resulting in the failure of ΔUV control. Small reductions in the concentrations of target proteins or impurities would cause protein losses, which could be predicted by the modeling. The combination of target protein and impurity variations showed complicated effects on the process performance of continuous capture. A contour map was proposed to describe the comprehensive impacts under different situations, and nonoperation areas could be identified due to control failure or protein loss. With the model-based approach, after the model parameters are estimated from the breakthrough curves, it can rapidly predict the process stability under dynamic control and assess the risks under feedstock variations or UV signal drifts. In conclusion, the model-based approach is a powerful tool for continuous process evaluation under dynamic changes and would be useful for establishing a new real-time dynamic control strategy.

Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with OCRL Mutations.

Background: Both Lowe syndrome and Dent-2 disease are caused by variants in the OCRL gene. However, the reason why patients with similar OCRL gene mutations presented with different phenotypes remains uncertain. Methods: Children with hemizygous pathogenic or likely pathogenic variants in OCRL were compiled from published and unpublished consecutive cases from China. Furthermore, a Chi-square test was employed to analyze the correlation of the location and types of mutations on the phenotype of children with Lowe syndrome or Dent-2 disease. Results: Among the total 83 patients, 70.8% (34/48) cases of Lowe syndrome presented with truncating mutations, while only 31.4% (11/35) cases of Dent-2 disease presented with truncating mutation (Χ2 = 12.662; P < 0.001). Meanwhile, the majority of mutations in Dent-2 disease are located in Exon 2-12 (21/35, 60.0%), while the majority of mutations in Lowe syndrome are located in Exon 13-23 (39/48, 81.3%; Χ2 = 14.922; P < 0.001). Conclusions: Truncating mutations of the OCRL gene were more common in patients with Lowe syndrome than in Dent-2 disease, while mutation is more likely located at exon 2-12 in Dent-2 disease than that in Lowe syndrome. The type and location of mutation are important indicators for the phenotypes in patients with OCRL mutation. This is a large cohort study analyzing the genotype-phenotype correlation in patients with Lowe syndrome and Dent-2 disease in China. Our data may improve the interpretation of new OCRL variants and genetic counseling. Furthermore, a large international study would be necessary to illustrate the genotype-phenotype correlation in patients with OCRL mutations.