The burden of tuberculosis among adolescents and young adults in five Asian countries from 1990 to 2019.

BACKGROUND: Previous studies have shown that the risk of tuberculosis (TB) increases dramatically during adolescence. The objective of this article was to analyze the burdens and trends of TB incidence and mortality rates in Asian adolescents and young adults. METHODS: Time series ecological study of TB incidence and mortality rates of adolescents and young adults aged 10-24 years from 1990 to 2019, using data extracted from the Global Burden of Disease website for 5 Asian countries. The annual percentage change was calculated by joinpoint regression analysis to estimate the trends in the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). RESULTS: The highest ASIR per 100,000 person-years in 2019 was in Mongolia [74 (95% uncertainty interval (UI), 51 to 105)], while the lowest was in Japan [4 (95% UI, 2 to 6)]. The highest ASDR per 100,000 person-years was in Mongolia [2 (95% UI, 1 to 3)], while the lowest was in Japan [0.009 (95% UI, 0.008 to 0.010)]. As the absolute number of cases and deaths decreased from 1990 to 2019, the ASIRs and ASDRs in all five countries also decreased. CONCLUSIONS: Our finding revealed that although all five countries in Asia experienced descending TB incidence and mortality trend in past three decades, the trends were especially significant in developed countries and varied across geographic regions. This study may be crucial in helping policymakers make decisions and allocate appropriate resources to adolescent TB control strategies.

CD19+CD5+ B cells in primary IgA nephropathy.

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.

CCL19 and CXCL13 synergistically regulate interaction between B cell acute lymphocytic leukemia CD23+CD5+ B Cells and CD8+ T cells.

Interacting with T cells, cytokine-producing B cells play a critical protective role in autoimmune diseases. However, the interaction between malignant B and T cells remains to be fully elucidated. In a previous study, we have reported that ligation of CCL19-CCR7 and CXCL13-CXCR5 activates paternally expressed gene 10 (PEG10), resulting in an enhancement of apoptotic resistance in B-cell acute lymphocytic leukemia (B-ALL) CD23+CD5+ B cells. Here, we report that B-ALL CD23+CD5+ B cells produce IL-10 at high level, which can be further elevated by costimulation with CCL19 and CXCL13. CCL19/CXCL13-activated B-ALL CD23+CD5+ B cells, in turn, increase IL-10 expression in syngeneic CD8+ T cells in a B cell-derived IL-10-dependent manner and requiring a cell-cell contact. IL-10 secreted from B-ALL CD23+CD5+ B cells in vitro impairs tumor-specific CTL responses of syngeneic CD8+ T cells. The impairment of cytotoxicity of syngeneic CD8+ T cells is escalated by means of CCL19/CXCL13-induced up-regulation of IL-10 from B-ALL CD23+CD5+ B cells. Moreover, using a short hairpin RNA to knockdown PEG10, we provide direct evidence that increased expression of PEG10 in B-ALL CD23+CD5+ B cells is involved in malignant B-T cell interaction, contributing to the up-regulation of IL-10 expression, as well as to the impairment of cytotoxicity of syngeneic CD8+ T cells. Thus, malignant B-ALL CD23+CD5+ B cells play an immunoregulatory role in controlling different inflammatory cytokine expressions. IL-10 may be one of the critical cellular factors conferring B-ALL CD23+CD5+ B cells to escape from host immune surveillance.