Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members.

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable

Corneal collagen crosslinking in patients treated with dextran versus isotonic hydroxypropyl methylcellulose (HPMC) riboflavin solution: a retrospective analysis

Abstract Background Corneal collagen crosslinking (CXL) is a widely used treatment for halting the progression of keratoconus. Although initial studies of CXL were performed with a riboflavin solution containing dextran, recent protocols for CXL have indicated the use of a riboflavin solution containing isotonic hydroxypropyl methylcellulose (HPMC). This study was performed to investigate differences in visual outcomes and Scheimpflug (Pentacam) analysis in patients who have undergone epithelium-off CXL with riboflavin solution containing either 20% dextran versus 1.1% HPMC. Methods All patients in this non-randomized, non-masked, retrospective cohort analysis were treated at Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, NY, USA. Thirty-seven eyes of 33 patients were crosslinked with a dextran solution and 19 eyes of 19 patients crosslinked with an isotonic HPMC solution, both using an epithelium-off 30-min, 3 mW/cm2 protocol. All patients had a diagnosis of keratoconus or post-refractive surgery ectasia. Best spectacle corrected visual acuity (BSCVA) and Pentacam parameters were compared at all follow up visits (1, 6, 12, and 24 months). Differences between groups treated with HPMC and dextran were compared using student’s t-test. Differences between treated eye and fellow eye were calculated and compared between HPMC and dextran groups using paired t-test. Results Patients treated with a dextran solution had significantly greater improvement in BSCVA at 1, 6, and 24 months (p < 0.05) compared to the isotonic HPMC-treated group. Kmax increased in both groups at 1 month; however, HPMC-treated patients had a greater increase compared to dextran-treated patients (p = 0.01). Kmax decreased in both groups at 6 and 12 months, although this finding was only significant in the HPMC-treated group at 12 months. Conclusions Our data suggest that crosslinking with the dextran solution may result in significantly better visual outcomes (demonstrated by visual acuity) compared to the isotonic HPMC riboflavin solution. Dextran solutions may have other potential advantages intrinsic to its biochemical properties facilitating more efficient crosslinking. Further research and long-term evidence regarding the use of dextran versus HPMC riboflavin solutions in collagen crosslinking is necessary