Immunotherapy choice and maintenance for generalized myasthenia gravis in China

AimsTo compare long‐term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real‐world settings.MethodsThis is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.ResultsAmong 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0‐62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower‐dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).ConclusionsRituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.     

Comparison of anatomical and visual outcomes following different anti-vascular endothelial growth factor treatments in subretinal neovascular membrane secondary to type 2 proliferative macular telangiectasia

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and visual outcomes following different...     

Composition and plasticity of triple-negative breast carcinoma-infiltrating regulatory T cells

Low Foxp3⁺ regulatory T-cell (Treg) presence in the tumor-infiltrating lymphocytes (TILs) is considered favorable in breast cancer, and numerous CD25-targeting agents have been applied in the attempt to remove Foxp3⁺ Treg cells, which typically present CD4⁺CD25^+/hi surface phenotype. However, CD25 is not Treg-exclusive and can be upregulated by effector T cells. Hence, CD25 depletion may cause the elimination of activated T cells that are responding to tumor-specific antigens. In this study, the composition and function of CD4⁺CD25⁺ cells inside the microenvironment of triple-negative breast carcinoma (TNBC) were investigated. Directly ex vivo, the Foxp3⁺ Treg cells represented a minor subset in total CD4⁺CD25⁺ TILs. Significant differences were observed in the expression of Treg-associated molecules between CD4⁺CD25⁺Foxp3⁺ TILs and CD4⁺CD25⁺Foxp3⁻ TILs. While both the CD4⁺CD25⁺Foxp3⁺ and the CD4⁺CD25⁺Foxp3⁻ TILs could express CTLA-4 and LAG-3, the expression levels were significantly higher in CD4⁺CD25⁺Foxp3⁺ TILs than in CD4⁺CD25⁺Foxp3⁻ TILs. Upon TCR stimulation, the expression of TGF-beta was significantly higher in CD4⁺CD25⁺Foxp3⁺ TILs, while the expression of IL-10 was significantly higher in CD4⁺CD25⁺Foxp3⁻ TILs. These differences were conserved in the blood counterparts of these cells. Interestingly, the level of CD25⁺Foxp3⁺ cells in circulating CD4⁺ T cells was positively correlated with the level of CD25⁺Foxp3⁺ cells in CD4⁺ TILs, but the level of CD25⁺Foxp3⁻ cells in circulating CD4⁺ T cells was not associated with the level of CD25⁺Foxp3^- cells in CD4⁺ TILs. Th17-polarizing medium could readily remodel CD4⁺CD25⁺Foxp3⁻, but not CD4⁺CD25⁺Foxp3⁺, T cells into RORgammat and IL-17-expressing T cells, demonstrating stronger plasticity of the former subset. Together, these data demonstrated that the CD4⁺CD25⁺ TILs were composed of distinctive Foxp3⁻ and Foxp3⁺ cells, with the former representing the major subset. The antigen specificity and effector molecule expression of the CD4⁺CD25⁺Foxp3⁻ thus require further analyses.