Relationships of varicella zoster virus (VZV)-specific cell-mediated immunity and persistence of VZV DNA in saliva and the development of postherpetic neuralgia in patients with herpes zoster

There are no surrogate markers for the development of postherpetic neuralgia (PHN) in patients with herpes zoster (HZ). All patients with HZ were prospectively enrolled to evaluate the associations of saliva varicella zoster virus (VZV) DNA persistence and VZV-specific cell-mediated immunity (CMI) with the development of PHN. Slow clearers were defined if salivary VZV DNA persisted after day 15. Salivary VZV was detected in 60 (85.7%) of a total of 70 patients with HZ on initial presentation. Of 38 patients for whom follow-up saliva samples were available, 26 (68.4%) were classified as rapid clearers and 12 (31.6%) as slow cleares. Initial VZV-specific CMI was lower in slow clearers than rapid clearers (median 45 vs 158 spot forming cells/10 ⁶ cells, P = .02). Of the 70 patients with HZ, 22 (31.4%) eventually developed PHN. Multivariate analysis showed that slow clearers (OR, 15.7, P = .01) and lower initial VZV-specific CMI (OR, 13.8, P = .04) were independent predictors of the development of PHN, after adjustment for age and immunocompromised status. Initial low VZV CMI response and persistence of VZV DNA in saliva may be associated with the development of PHN.     

Understanding and measuring human B‐cell tolerance and its breakdown in autoimmune disease

The maintenance of immunological tolerance of B lymphocytes is a complex and critical process that must be implemented as to avoid the detrimental development of autoreactivity and possible autoimmunity. Murine models have been invaluable to elucidate many of the key components in B‐cell tolerance; however, translation to human homeostatic and pathogenic immune states can be difficult to assess. Functional autoreactive, flow cytometric, and single‐cell cloning assays have proven to be critical in deciphering breaks in B‐cell tolerance within autoimmunity; however, newer approaches to assess human B‐cell tolerance may prove to be vital in the further exploration of underlying tolerance defects. In this review, we supply a comprehensive overview of human immune tolerance checkpoints with associated mechanisms of enforcement, and highlight current and future methodologies which are likely to benefit future studies into the mechanisms that become defective in human autoimmune conditions.     

Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer

Immunologic Research - The expression of major histocompatibility complex class I (MHC I) in tumor cells is regulated by interferon signaling, and it is an important factor in the efficacy of...     

Enhanced Anti-Leukemic Effects through Induction of Immunomodulating Microenvironment by Blocking CXCR4 and PD-L1 in an AML Mouse Model

Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments.     

Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice

Chinese liver fluke Clonorchis sinensis changes the host’s immune system. Recently, it has been reported that helminths including C. sinensis can ameliorate immune-related diseases such as allergy. In addition, recent studies showed that helminth infection can alleviate immune-mediated disorders by altering the gut microbiome. However, changes in the gut microbiome due to C. sinensis have not been reported yet. In this study, changes in the gut microbiome of C57BL/6 mice infected with C. sinensis metacercariae were evaluated over time. Stool was analyzed by 16S rRNA amplicon analysis using high-throughput sequencing technology. There was no apparent difference in species richness and diversity between the infected and control groups. However, the composition of the microbiome was different between the infected and control groups at 20 days and 30 days post-infection, and the difference disappeared at 50 days post-infection. In particular, this microbiome alteration was associated with a change in the relative abundance of genus Lactobacillus and the probiotic Lactobacillus species that are known to have an immune-modulation role in immune-mediated diseases.

     

Residual varus alignment after total knee arthroplasty increases knee adduction moment without improving patient function: A propensity score-matched cohort study

BackgroundTargeting residual varus alignment in total knee arthroplasty may be functionally beneficial to preoperative varus patients.MethodsBilateral TKA patients were enrolled. According to the postoperative hip-knee-ankle axis, patients were allocated into residual varus (3° ± 1°) alignment group or neutral (0° ± 1°) alignment group. Then, 1:2 propensity score matching was used to match preoperative variables. Finally, matched neutral (n = 45) and varus groups (n = 32) were followed-up for two years and compared. The primary outcome was the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were range of motion (ROM), Knee Society knee score and function score, spatiotemporal gait parameters, dynamic alignment, knee flexion angle, knee adduction moment (KAM) and internal knee extension moment.ResultsAt two years after surgery, the mean difference of WOMAC score was 0.3 (95% CI, [? 3.1, 3.7]) between the two groups. All secondary outcomes, except KAM and dynamic alignment, showed no significant difference between the two groups. Residual varus alignment group showed increased KAM and maximum KAM was 19% higher (P = 0.006).ConclusionsResidual varus alignment showed no clinical benefits, and both groups of patients had a functionally identical knee gait biomechanics, except for increased KAM and varus alignment. The authors consider that even in patients with varus alignment, the first principle is still achieving neutral alignment, which is helpful for reducing the KAM.Level of evidenceIII, retrospective cohort study.