Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL.

While systemic lupus erythematosus (SLE) is known to involve heightened pro-inflammatory cytokine production within immune cells, a knowledge gap exists regarding the specific cytokine profile of circulating hematopoietic stem progenitor cells (HSPCs) in SLE patients. This study aims to address this by investigating the expression of key inflammatory cytokines within this specific cell population and to elucidate whether hydroxychloroquine (HCQ) treatment can regulate inflammatory cytokines of HSPCs in these patients. This investigation employed an in vitro approach to analyze the anti-inflammatory cytokine (TGF-β) and the pro-inflammatory cytokines (IL-6 and IL-17) expression profile in HSPCs derived from leukapheresis of both SLE and healthy control subjects. Flow cytometry was employed to analyze cytokine expression. Following a 72-hour incubation, we assessed the potential impact of 5 µM and 25 µM HCQ on the expression of IL-6, IL-17, and TGF-β by HSPCs. Circulating HSPCs from SLE patients exhibited significantly higher levels of inflammatory cytokines compared to healthy controls. Notably, HCQ treatment at concentrations of 5 µM and 25 µM significantly down-regulated IL-17 expression in SLE-derived HSPCs compared to the untreated control group (p < 0.0001). Interestingly, HCQ did not impact IL-6 levels in SLE subjects. TGF-β levels remained unchanged following HCQ treatment in both groups. These observations suggest a potential role for HCQ in specifically reducing IL-17 in SLE patients. This in vitro study provides evidence for heightened pro-inflammatory cytokine production within cultured HSPCs isolated from SLE patients. Furthermore, HCQ treatment demonstrates a potential capacity to inhibit this pro-inflammatory cytokine production in the SLE context.

CoronaVac emerged as one of the most widely administered COVID-19 vaccine in Indonesia. Previous research has documented various figures regarding its effectiveness in protecting against COVID-19 in several countries. Therefore, this research aims to assess the long-term immunogenicity profile in individuals with comorbidities or history of SARS-CoV-2 infection. The level of total anti-N Ig and anti-S-RBD Ig at 7 weeks and 26 weeks after receiving the second dose was observed in 194 health workers. The participants were divided into groups based on their comorbidities and history of SARS-CoV-2 infection. The results showed that there was no difference in both antibody titers between healthy and comorbid groups without any history of SARS-CoV-2 infection. The level of total anti-nucleocapsid Ig was significantly lower compared to the infected groups, and similar results were obtained in the total anti-S-RBD Ig level. Based on the results, CoronaVac induced a lower specific antibodies response compared to natural infection and also reduced immunogenicity in the long term.

Systemic Lupus Erythematosus (SLE) is a medical condition characterized by an abnormal immune response that affects multiple organs and tissues, resulting in a range of symptoms and potential problems. To confirm or exclude a diagnosis of systemic lupus erythematosus (SLE), it is necessary to conduct tests for anti-nuclear antibody (ANA) and anti-DFS70 antibody. The most widely accepted and reliable approach for detecting antinuclear antibodies (ANA) is the indirect immunofluorescent test (IIFA), which is known for its complexity and high cost. Therefore, it is imperative to create a more cost-effective and simplified test for the detection of ANA and anti-DFS70 antibodies. Our preliminary study aimed to isolate sensitive and specific antigens for the detection of ANA and anti-DFS70 antibodies using the dot blot method. Nuclear antigens were isolated from leukocytes of SLE patients who underwent leukapheresis. DSF70 antigens were obtained from R&D Systems (RH-LEDGF cat.no 3468-LE, Lot: ODX0819071). Nuclear antigens and DFS70 antigen were attached to the nitrocellulose membrane dot blot with a dilution of 0.01 mcg/mL and 0.1 mcg/mL, respectively. Furthermore, the antigens were tested for sensitivity and specificity in 56 SLE patients and 34 healthy controls. As a comparison for ANA and anti-DFS70 antibody tests, the ELISA methods were used. The sensitivity and specificity of dot blot methods using the nuclear antigen were 61.5% and 84.6% and the DSF70 antigen were 45.5% and 82.3%, respectively. There were moderate sensitivity and good specificity dot blot methods using both nuclear and DFS-70 antigens for ANA and anti-DFS70 antibody detection. The method of nuclear antigen preparation still needs to be modified to improve its sensitivity.

Background SLE is distinguished by the development of multiple autoantibodies that lead to chronic inflammation and increased risk of cardiovascular diseases, especially atherosclerosis. Objective This examination sought to explore the association between the disease activity, clinical manifestations, and medication with the atherosclerotic lesion from SLE patients. Methods This inquiry investigated forty-two female SLE patients (18-45 years old) who met the 2019 EULAR/ACR assortment decency with matched healthy individuals as control A cross-sectional study was sanctioned at the Rheumatology Clinic of Saiful Anwar General Hospital Malang between July and November 2023. Demographic data, clinical manifestations, and medication history was documented in the medical records. Disease activity was stelled by the SLEDAI-2K score. Carotid Intima-Media Thickness (cIMT) and Flow-Mediated Dilation (FMD) (after brachial BP cuff inflation up to 200 mmHg for five minutes) examinations were used as atherosclerosis marker. Results Markedly higher of cIMT mean was demonstrated in SLE patients compared to healthy individual (0.51±0.11 vs 0.40±0.11 mm, p<0.001). FMD was subtancially curtailed in SLE patients set side to side to control (0.00 (0.00-0.10) vs 0.10 (0.00-0.28) mm, p=0.022). There was no statistical distinctness of the cIMT and FMD among SLE patients according to the presence of clinical manifestations. Neither cIMT nor FMD showed a statistically correlated with the disease activity. Patients who received hydroxychloroquine (0.57±0.02 vs. 0.50±0.09 mm, p=0.043) and cyclophosphamide (0.55±0.09 vs. 0.48 ± 0.10 mm, p=0.031) had higher cIMT. Higher cIMT was demonstrated in subjects who received steroid (p=0.045) and the dosage of steroid was essentially enforced to cIMT (R=0.418, p=0.034). Conclusion Our study unveil that early atherosclerosis was evidenced in patients with SLE and several medications might affect the progressivity of atherosclerosis. Keywords: Systemic lupus erythematosus, atherosclerosis, disease activity, medication, clinical manifestations

Background: The immune cells of patients with systemic lupus erythematosus (SLE) age earlier than those of normal subjects. However, the senescence of circulating hematopoietic stem cells (HSCs) in patients with SLE is not well understood, and it is unclear whether zinc treatment can regulate the senescence and proinflammatory cytokine production of HSCs in these patients. Methods: Clinical data were collected on 38 patients with SLE and 35 healthy controls (HCs), and the complete blood count, circulating HSC number, and p16 (a senescence marker) expression in the peripheral blood of these participants were analyzed via flow cytometry. Pooled circulating HSCs were isolated using leukapheresis. The effects of zinc chloride exposure on the pooled HSCs of each group were determined in vitro. Levels of the proinflammatory cytokines IL-6 and IL17, regulatory cytokine TGF-β, p16, and regulator T-cells (Tregs) were evaluated 72 h after incubation with 50 or 100 µM zinc chloride. Results: The number of circulating HSCs did not differ between the two groups (p=0.1685). The expression of p16 in HSCs was higher in the SLE group than in the HC group (p = 0.0043), and patients with SLE exhibited higher levels of IL-6, IL-17, and p16 in pooled HSCs (p =0.0025, p<0.0001, and p = 0.0003, respectively), although TGF-β levels did not differ between the groups (p=0.9816). Zinc chloride reduced IL-6, TGF-β, IL-17, and p16 expression in patients with SLE toward HC levels. Treg frequency in pooled HSCs was comparable between the groups (p=0.3997), although a 100 µM zinc chloride treatment significantly depleted the Treg population of patients with SLE (p=0.0001). Conclusions: Circulating HSCs in SLE are more aged and produce more proinflammatory cytokines. Zinc chloride treatment might prevent immunoaging and inhibit proinflammatory cytokine–producing cells in patients with SLE.