Anti-CD5 Monoclonal antibody, clone 64-8.4 [FITC]

Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-alpha, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.

Mouse models of multiple sclerosis (MS) have shown the importance of interleukin-10 (IL-10) -producing regulatory B (Breg) cells in dampening disease activity and inhibiting disease initiation and progression. In MS and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL-10-producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON) is a common first clinical manifestation of MS and IL-10-producing Breg cells may be crucial in the transition from ON to MS, we therefore investigate the frequency and function of Breg cells in ON as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON sampled close to symptom onset (median 23 days, range 7-41 days) and 13 healthy controls. The B cells were stimulated and cultured for 48 hr with CD40 ligand and CpG before measurement of intracellular IL-10 and the surface markers CD19, CD1d, CD5, CD24, CD38 and CD27 by flow cytometry. The frequency of B-cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF) of patients. Sixty-five per cent of the IL-10-producing Breg cells co-expressed CD24 and CD38, and only 14% were CD24(high) CD27(+), suggesting that the naive B cells are the primary source of IL-10 in the B-cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD19(+) CD24(+) CD38(+) Breg cells was higher in patients with ON compared with controls. The ability of Breg cells to produce IL-10 was at normal levels in both ON patients with high risk and those with low risk of progression to MS. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF oligoclonal bands indicative of ON patients carrying a higher risk of conversion to MS. The frequencies of IL-10-producing B cells did not correlate with the conversion to MS at 2-year follow up. Interleukin-10 was primarily produced by naive and memory B cells. The frequency of IL-10-secreting B cells did not correlate with risk factors of MS. Breg cell function at clinical onset of ON is not a determining factor for conversion to MS.