Poor allograft outcome in Indian patients with post-transplant C3 glomerulopathy.

BACKGROUND: Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia. METHODS: In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for CFH/CFHR5 genes was carried out. All study patients were also followed up. RESULTS: A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8-17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic CFH gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died. CONCLUSION: Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor.

Translocation and toxicity of docetaxel multi-walled carbon nanotube conjugates in mammalian breast cancer cells.

Multi-walled-carbon nanotubes (MWNTs) are widely explored as carriers for drug delivery due to their facile transport through cellular membranes and are reportedly found to be effective against cancer. In the present study, we have evaluated cellular uptake of Docetaxel (DTX) conjugated MWNTs from human breast cancer cells (MCF-7 and MDA-mb-231) and have provided primary results on cytotoxicity of the same. Efficient internalization of the drug conjugate (DTX-MWNTs) inside the cell was corroborated with the help of confocal microscopy, transmission electron microscopy and flow cytometry. The comparison of cytotoxicity of the conjugate and DTX was done by MTT assay. Results of the study indicated increased efficacy of the conjugates over the drug in terms of their cytotoxicity. It was observed that such conjugation of drug to MWNTs can be explored as a strategy to improve therapeutic index of cytotoxic drugs such as DTX and thereby enriching cancer therapies of coming time.