This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection.
Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR.
Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4+ T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double-positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh-cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc-cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them.
Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention.
© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Acute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.
Paired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19+ and CD138+ on liver tissues was examined by immunohistochemistry staining.
In this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27+CD21- activated memory B cells (AM), CD27-CD21- atypical memory B cells (atMBC), CD27+IgD-IgM+(IgM+ memory B cells), and CD27+CD38++ plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27+CD38++plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.
In this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.
Copyright © 2022 Zhao, He, Wang, Cui, Yang, You, Shi, Xia and Chen.

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible.
In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20-containing treatment. This article is highlighted in the In This Issue feature, p. 85.
©2022 American Association for Cancer Research.

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. In the present study, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B cells, we show that enhancer-promoter-interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacological depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intrachromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulates interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.

Hepatitis C virus (HCV) infection is associated with B cell abnormality; however the phenotypic profiles of immunoglobulin (Ig)M+B cell subsets in patients with HCV infection remain unclear. In the current study, the effect of HCV infection on IgM+B cell subsets was evaluated. The percentages, as well as the differentiation and activation features of peripheral IgM+B naive subsets [cluster of differentiation (CD)27-IgM+B cells] and IgM+B memory subsets (CD27+IgM+B cells) were assessed using flow cytometry in 27 patients with chronic hepatitis C (CHC) and 20 healthy controls (HCs). The frequency of CD27+IgM+B memory subsets detected in patients with CHC was significantly higher than that in HCs (P<0.05). Although the frequency of CD27-IgM+B naive subsets was similar in both groups, there was a significantly higher proportion of CD5+B cells detected in the CD27-IgM+B subsets of patients with CHC compared with HCs (P<0.05). Among CD27-IgM+B subsets, abnormal differentiation was associated with HCV infection, with significantly increased percentages of IgD+B cells and CD38+B cells in patients with CHC compared with HCs (P<0.05). In CD27+IgM+B memory subsets, the abnormality of cell differentiation was associated with a significantly increased percentage of CD38+B cells in patients with CHC compared with HCs (P<0.05). In addition, the percentage of activated CD27+IgM+B subsets in patients with CHC were significantly higher than those observed in HCs (P<0.05). The number of CD27-IgD+IgM+B, CD27-CD38+IgM+B and CD27+CD38+IgM+B cells were negatively correlated with HCV RNA in patients with CHC. These results suggest that HCV infection contributes to abnormalities in the percentage, differentiation and activation of IgM+B cell subsets and may disrupt the immune response mediated by IgM+B cells.