Aim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sjögren syndrome (pSS) and in pSS-associated lymphomas.
29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMCs).
IL-40 was significantly increased in the lymphocytic infiltrated MSG of patients with pSS and correlated with focus score and with IL-4 and transforming growth factor-β expression. In addition, IL-40 was increased in the serum of pSS and its levels correlated with the EULAR Sjögren's Syndrome Disease Activity Index score. B cells from patients were shown to be the major source of IL-40 at both tissue and peripheral level. PBMCs from patients, exposed to rIL-40 in vitro, released proinflammatory cytokines, specifically interferon-γ from B cells and T-CD8+ and tumour necrosis factor-α and IL-17 from both T-CD4+ and T-CD8+. IL-40 expression in parotid glands of pSS-associated lymphomas was also increased. Moreover, IL-40-driven NETosis was evidenced in neutrophils obtained from pSS.
Our results suggest that IL-40 may play a role in pSS pathogenesis and pSS-associated lymphomas.
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Acute promyelocytic leukemia (APL) during pregnancy is rare and difficult to treat. To the best of our knowledge, there is little precedent for successful treatment with combined chemotherapeutic agents without affecting delivery. The present study reported the case of a 31-year-old woman pregnant with twins who presented to the antenatal service at 13-week gestational age with complaints of vaginal bleeding, lower abdominal pain, bleeding gums and skin ecchymosis, and was eventually diagnosed with APL. After treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction regimen, the patient achieved a complete remission (CR) and delivered two healthy male infants at 34 weeks of gestation. The use of ATRA and ATO for the treatment of APL is controversial due to teratogenic effects and lethal retinoic acid syndrome. However, the patient demonstrated that the chemotherapy regimen with ATRA and ATO during the second and third trimesters can result in a sustainable remission and successful pregnancy outcome.
Copyright © 2020, Spandidos Publications.

X-linked chronic granulomatous disease (CGD) is associated with defective phagocytosis, life-threatening infections, and inflammatory complications. We performed a clinical trial of lentivirus-based gene therapy in four patients (NCT02757911). Two patients show stable engraftment and clinical benefits, whereas the other two have progressively lost gene-corrected cells. Single-cell transcriptomic analysis reveals a significantly lower frequency of hematopoietic stem cells (HSCs) in CGD patients, especially in the two patients with defective engraftment. These two present a profound change in HSC status, a high interferon score, and elevated myeloid progenitor frequency. We use elastic-net logistic regression to identify a set of 51 interferon genes and transcription factors that predict the failure of HSC engraftment. In one patient, an aberrant HSC state with elevated CEBPβ expression drives HSC exhaustion, as demonstrated by low repopulation in a xenotransplantation model. Targeted treatments to protect HSCs, coupled to targeted gene expression screening, might improve clinical outcomes in CGD.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Cationic host defense peptides (HDPs) are a promising alternative to antibiotics in the fight against Staphylococcus aureus infections. In this study, we investigated the antibacterial and immunomodulatory properties of three HDPs namely IDR-1018, CATH-2, and LL-37. Although all three HDPs significantly inhibited LPS-induced activation of human macrophages, only CATH-2 prevented S. aureus growth. When applied to different infection models focused on intracellularly surviving bacteria, only IDR-1018 showed a consistent reduction in macrophage bacterial uptake. However, this observation did not correlate with an increase in killing the efficiency of intracellular S. aureus. Here, we conclude that despite the promising antibacterial and anti-inflammatory properties of the selected HDPs, macrophages' intrinsic antibacterial functions were not improved. Future studies should either focus on combining different HDPs or using them synergistically with other antibacterial agents to improve immune cells' efficacy against S. aureus pathogenesis.
© 2022 The Author(s).

Although the concept of "myeloid neoplasm continuum" has long been proposed, few comparative genomics studies directly tested this hypothesis. Here we report a multi-modal data analysis of 730 consecutive newly diagnosed patients with primary myeloid neoplasm, along with 462 lymphoid neoplasm cases serving as the outgroup. Our study identified a "Pan-Myeloid Axis" along which patients, genes, and phenotypic features were all aligned in sequential order. Utilizing relational information of gene mutations along the Pan-Myeloid Axis improved prognostic accuracy for complete remission and overall survival in adult patients of de novo acute myeloid leukemia and for complete remission in adult patients of myelodysplastic syndromes with excess blasts. We submit that better understanding of the myeloid neoplasm continuum might shed light on how treatment should be tailored to individual diseases.
The current criteria for disease diagnosis treat myeloid neoplasms as a group of distinct, separate diseases. This work provides genomics evidence for a "myeloid neoplasm continuum" and suggests that boundaries between myeloid neoplastic diseases are much more blurred than previously thought.
© 2022 The Authors; Published by the American Association for Cancer Research.