Genetic polymorphisms effect on cyclophosphamide's tolerability and clinical efficacy in Egyptian patients with lupus nephritis.

OBJECTIVES: Many studies were conducted to determine the association between genetic polymorphisms in CYP2B6 c.516G>T and cyclophosphamide (CYC) efficacy or toxicity, no studies were focused on both clinical efficacy and toxicity of CYC. This study aimed to investigate the relationship between the CYP2B6 c.516G>T polymorphism (rs 3745274) and 17 different parameters related to CYC efficacy and tolerability in Egyptian patients with lupus nephritis (LN). METHODS: A prospective cohort study on 142 LN patients with a mean age of 36.26 was conducted at Kasr Al Ainy School of Medicine, Cairo University, Egypt after the exclusion of 14 patients due to receiving an interacting medication with CYC. All clinical parameters related to CYC efficacy or toxicity were recorded and compared between the different genotypes. RESULTS: There was a statistically significant difference between different genotypes in 11 out of 13 of the studied efficacy-related parameters. Many of the studied clinical parameters revealed that CYC's efficacy was associated with the presence of the T allele. There was a statistically significant difference between different genotypes in hepatotoxicity, diarrhea, and blood-related toxicities. CONCLUSION: To our knowledge, this study is the first study that focused on studying 17 different parameters related to CYC efficacy and tolerability. Our findings paint a picture of the function that CYP2B6 polymorphisms play in Egyptian LN patients. Pre-treatment evaluation of CYP2B6 rs 3745274 may account for some individual differences in treatment response.

Lab-scale production of anti-Schistosoma monoclonal antibodies by hybridoma culturing in serum free medium: Enhancement of growth, cryopreservation survival rate, and diagnostic accuracy.

This study was performed to evaluate the effect of two commercially available serum-free culture media; serum free medium (SFM) and chemically defined medium (CDM), on the growth rate, antibody productivity and post adaptation cryopreservation and revival reactivity of hybridoma cells compared to the conventional serum based medium (SBM). In addition, the diagnostic efficacy of MAbs secreted in each culture medium was evaluated by testing their performance in sandwich ELISA for antigen detection. Anti- Schistosoma mansoni soluble egg antigen hybridoma cell line (7A/8F) secreting previously characterized IgG Kappa mAbs, were retrieved and propagated in each of the three aforementioned media. Growth rate and viability were assessed post culturing in each media. The data collected from this study indicated that MAbs secreted from hybridoma cells cultured in SFM were the most abundant, easiest to purify, and the most effective in antigen detection by sandwich ELISA, in comparison to those produced in the other two media. Moreover, combination of fresh and conditioned medium with DMSO 7.5% was the most promising formulation for the cryopreservation of hybridoma cells cultivated in serum independent media (SFM or CDM).