Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis,with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-␣ treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsyproven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-␣ and/or PEGylated interferon-␣. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio ؍ 2.51; 95% confidence interval, 1.28-5.52; P ؍ .006) in our cohort. Conversely, treatment with interferon-␣ was identified as an independent predictor of survival (hazard ratio ؍ 0.32; 95% confidence interval, 0.14-0.70; P ؍ .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-␣ improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality. (Blood. 2011;117(10):2778-2782)
An acute exacerbation of Th1 responses against mycobacterial antigens appears to cause IRS in patients co-infected with HIV and TB. This key event provides new evidence valuable for the diagnosis and treatment of IRS.
Tuberculosis (TB)-associated immune restoration syndrome (IRS) is a frequent event (10 to 30%) in HIV-1-infected patients receiving antiretroviral treatment and is associated with an increased number of IFN-γ-producing tuberculin-specific cells. To further understand the immune mechanisms of TB-IRS and to identify predictive factors, we prospectively analyzed the Th1 and TCRγδ T cells known to be involved in mycobacterial defenses and dendritic cells at baseline and after antiretroviral and TB treatment in 24 HIV-1+ patients, 11 with and 13 without IRS. At baseline, these two groups differed by significantly lower proportions of TCRγδ and Vδ2+ T cells displaying the inhibitory receptors CD94/NKG2 and CD158ah,b in IRS patients. The two groups did not differ in the baseline characteristics of CD8 or CD4 T cells or TLR-2 expression on monocytes or myeloid/plasmacytoid dendritic cells. During IRS, the increase in tuberculin-specific IFN-γ-producing cells involved only highly activated effector memory multifunctional (IFN-γ+TNF-α+IL-2−) CD4 T cells, whereas activated HLA-DR+ CD4+ T cells also increased during IRS. In contrast, dendritic cells decreased significantly during IRS and there were no changes in TLR-2 expression. Finally, the Vδ2+ T cells, mostly killer Ig-related receptor (KIR) (CD94/NKG2− and CD158−), significantly peaked during IRS but not in non-IRS patients. In conclusion, IRS is associated with an increase in the number of activated tuberculin-specific effector memory CD4 T cells and of KIR−Vδ2+ TCRγδ+ T cells. Higher proportions of Vδ2+TCRγδ+ T cells lacking KIR expression are present as baseline and distinguish patients who will develop IRS from those who will not.
HIV-associated multicentric Castleman disease (MCD) is associated with a high risk of developing nonHodgkin lymphoma (NHL). Rituximab is effective in HIV-MCD, but its impact on NHL incidence remains unknown. From a single-center prospective cohort, 113 patients were identified with a diagnosis of HIV-MCD for the present study. To compare the incidence of NHL between patients who had received a rituximab-based treatment (R؉ group) and those who had not (R؊ group), data were analyzed before and after matching on propensity scores and after multiple imputation. The mean follow-up was 4.2 years. In the R؊ group (n ؍ 65), 17 patients developed NHL (incidence, 69.6 of 1000 person years). In the R؉ group (n ؍ 48), only 1 patient developed NHL (incidence, 4.2 of 1000 person years). Based on the propensity score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio, 0.09; 95% confidence interval, 0.01-0.70). Ten Kaposi sarcoma (KS) exacerbations and 1 newly diagnosed KS were observed in 9 patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy. (Blood. 2012;119(10):2228-2233)
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