The prevalence of antibody to hepatitis C virus (HCV) in a cohort of 272 HIV-infected patients was assessed by means of 4 anti-HCV assays: a 1st generation and a neutralization test, a 2nd generation test, and a confirmatory test, the dot-blot Matrix HCV immunoassay. The cohort included, as a single risk factor, 35.7% intravenous drug users (IVDUs), 25% homosexual men, 30.1% heterosexual individuals, 5.9% transfused patients, 0.7% occupational infections, and 2.6% patients with unknown infection source, and was studied on entry and in samples collected for up to 36 months. Results showed that on entry (i) sera of 83 out of 272 members of the cohort were positive by the HCV 1st generation EIA (30.5%); 70 were confirmed by the neutralization test (84.3%); (ii) 115 of the cohort were reactive with the 2nd generation HCV EIA (41.3%); (iii) with the dot-blot immunoassay 99 (86.1%) of the cohort were confirmed and 16 remained indeterminate. The overall confirmed HCV antibody-positive rate in these 272 patients was 36.4%. Antibody to HCV was detected in 78.3% of IVDUs, 18.3% of heterosexual individuals, 31.2% of transfused patients, and only 2.9% of homosexual men. The 36-month follow-up of this cohort revealed that 4/145 patients became anti-HCV positive by second generation assay. Hepatitis B markers were frequently associated with HCV in IVDUs (71.1%) but infrequently in heterosexual (8.5%) or homosexual (1.5%) individuals. Our results suggest that HCV 2nd generation EIA used in combination with the semiautomated dot-blot assay as a confirmatory test improves the specificity and sensitivity for HCV antibody detection.(ABSTRACT TRUNCATED AT 250 WORDS)
Induced pluripotent stem cells (iPSC) offer the possibility to generate diverse disease-relevant cell types, from any genetic background with the use of cellular reprogramming and directed differentiation. This provides a powerful platform for disease modeling, drug screening and cell therapeutics. The critical question is how the differentiated iPSC-derived cells translate to their primary counterparts. Our refinement of a published differentiation protocol produces a CD14+ monocytic lineage at a higher yield, in a smaller format and at a lower cost. These iPSC-derived monocytes can be further differentiated into macrophages or dendritic cells (DC), both with similar morphological and functional profiles as compared to their primary counterparts. Transcriptomic analysis of iPSC-derived cells at different stages of differentiation as well as comparison to their blood-derived counterparts demonstrates a complete switch of iPSCs to cells expressing a monocyte, macrophage or DC specific gene profile. iPSC-derived macrophages respond to LPS treatment by inducing expression of classic macrophage pro-inflammatory response markers. Interestingly, though iPSC-derived DC show similarities to monocyte derived DC, they are more similar transcriptionally to a newly described subpopulation of AXL+ DC. Thus, our study provides a detailed and accurate profile of iPSC-derived monocytic lineage cells.
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