Disease Activity Research Articles

TLR10 expression in unswitched memory B associates with the disease activity of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by impaired B-cell function and a distinct B-cell phenotype. Toll-like receptor (TLR) 10 is highly expressed in human B cells and can regulate B-cell activation. Here, we examined the variations in TLR10 expression across B-cell subpopulations and its impact on the disease activity in SLE patients. Thirty-one patients with stable SLE, 30 patients with active SLE, and 28 healthy controls (HCs) were recruited. Flow cytometry was performed to assess the prevalence of B-cell subpopulations and their TLR10 expression. The diagnostic value of unswitched memory B cells (UMB) and double-negative B cells (DNB) in relation to disease activity was determined. The correlations between TLR10 expressions in B-cell subpopulations and disease activity were further evaluated, respectively. Compared with the HCs, the stable patients exhibited significantly reduced Naive B proportion and elevated switched memory B and DNB proportion, while active patients presented markedly decreased UMB and increased DNB proportion. Furthermore, the receiver operating characteristics analysis revealed that UMB was more reliable than DNB in diagnosing SLE disease activity. Among the B-cell subsets, only the TLR10 expression in UMB was notably diminished in SLE patients, particularly in active patients. Importantly, TLR10 expression in UMB was negatively correlated with the disease activity. UMB could serve as a promising biomarker for SLE disease activity, and the TLR10 expression in UMB was negatively correlated with the activity of SLE patients, suggesting that TLR10 might be involved in the disease progression of SLE by regulating the UMB function. Key Points • Active SLE patients exhibited reduced unswitched memory B cells and increased double-negative B cell proportions in blood. • Unswitched memory B cells are better predictors of disease activity in SLE than double-negative B cells. • TLR10 expression in unswitched memory B cells is markedly diminished in SLE patients. • TLR10 expression in unswitched memory B cells is negatively associated with SLE disease activity.

The Relationship Between Systemic Immune Inflammatory Level and Dry Eye in Patients with Sjögren’s Syndrome

Background and objectives: Sjögren Syndrome (SS) is a chronic, systemic, and progressive autoimmune disease in which inflammatory processes play a role. Dry eyes or mouth are present in approximately 95–98% of patients with pSS. This study aimed to evaluate the relationship between SII level and disease activity as well as dry eye involvement in patients with pSS. Materials and methods: A cross-sectional design was employed, and a total of 28 female patients who were aged 18–65 years and were diagnosed with pSS were involved. The Sjögren Syndrome Disease Activity Index (ESSDAI) was calculated in patients. The Schirmer test was applied to all patients. The relationship between SII level and disease activity as well as dry eye involvement in pSS patients was evaluated. Results: In our study, a strong positive correlation was found between the SII value and pSS disease activity, while a negative correlation was found between the Schirmer test, which shows dry eye findings, and eye drying time, and a positive correlation was found with the OSDI. Conclusions: this study reported a correlation between hematological parameters and the development of dry eye in pSS. NLR, PLR, and SII showed statistically significant changes in pSS patients.

Clinical Presentation, Care Pathways, and Delays in Access to Specialized Care in Patients With Systemic Lupus Erythematosus: A Study From Lupus Midwest Network (LUMEN).

We aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 (95% confidence interval [CI] 0.9-1.5) months, time to diagnosis was 30.6 (95% CI 18.9-48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9-8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with disease-related damage. Fewer manifestations, hematologic manifestations, or antiphospholipidantibodies were associated with delays.

Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

Inebilizumab for Treatment of IgG4-Related Disease.

IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease. In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission. A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo. Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).

The Nancy Histopathological Index has limited value in predicting clinical outcomes in newly diagnosed pediatric patients with ulcerative colitis.

The Nancy Histological Index (NHI) is used to score histologic disease activity in patients with ulcerative colitis (UC). Our goal was to assess the utility of NHI at diagnosis in predicting clinical outcomes in pediatric patients with UC, in comparison to clinical and endoscopic scores. We retrospectively reviewed data at diagnosis of 106 children with UC (59 [55.7%] females; median age 14.4 [11.2-15.9] years, median Pediatric Ulcerative Colitis Activity Index [PUCAI] 35 [25-55]). During a follow-up of 116 (55-171) weeks, 33 patients (31.1%) required azathioprine therapy, and 32 (30.2%) were escalated to anti-tumor necrosis factor alpha (anti-TNFa). The PUCAI and Mayo endoscopic scores at diagnosis were significantly associated with escalation to anti-TNFa (p = 0.036 and p = 0.02, respectively), but not with initiation of azathioprine or subsequent acute severe colitis (ASC) events. However, the NHI was not associated with subsequent immunomodulators or anti-TNFa therapy (p = 0.42 and p = 0.78, respectively), nor with future ASC events (p = 0.70). In conclusion, the NHI failed to predict clinical outcomes in newly diagnosed pediatric patients with UC.

Regulation of Colonic Inflammation and Macrophage Homeostasis of IFN-γ-Primed Canine AMSCs in Experimental Colitis in Mice

Mesenchymal stem cells (MSCs) have shown potential in treating immune-mediated diseases due to their immunomodulatory properties, which can be enhanced by priming with inflammatory cytokines like interferon-gamma (IFN-γ). This study evaluates the therapeutic effects of IFN-γ-primed canine adipose tissue-derived MSCs (AMSCs) in a mouse model of inflammatory bowel disease (IBD). Canine AMSCs were primed with 50 ng/mL recombinant canine IFN-γ for 48 h, and the effects were compared to those seen in naïve (unprimed) AMSCs. IBD was induced in mice using dextran sodium sulfate (DSS), and AMSCs were injected intraperitoneally on days 1 and 3. The mice treated with IFN-γ-primed AMSCs showed improved clinical outcomes, including a reduced disease activity index (DAI), less body weight loss, and longer colon length compared to the mice treated with naïve AMSCs. A histological analysis revealed less damage to the intestinal structures and reduced inflammatory cell infiltration. IFN-γ priming led to a shift in the immune cell balance in the gut, decreasing pro-inflammatory macrophages (Ly6Chi) and increasing anti-inflammatory macrophages (Ly6Clo/MHC-IIhi). This was associated with the reduced expression of inflammatory cytokine genes (Il-1β, Il-6, and Il-18) and increased expression of the intestinal stem cell marker Lgr5. These findings suggest that IFN-γ-primed AMSCs offer enhanced therapeutic potential for treating CE in veterinary medicine.

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.

Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium

ObjectivesTo identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.MethodsIn the multicentre PsA Research Consortium...

Photoactivatable O-GlcNAc transferase library enables covalent chemical capture of solvent-exposed TPR domain interactions.

O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential, stress-sensing enzyme responsible for adding the O-GlcNAc monosaccharide to thousands of nuclear and cytoplasmic proteins to regulate cellular homeostasis. OGT substrates are found in almost all intracellular processes, and perturbations in protein O-GlcNAc levels have been implicated in proteostatic diseases, such as cancers, metabolic disorders, and neurodegeneration. This broad disease activity makes OGT an attractive therapeutic target; however, the substrate diversity makes pan-inhibition as a therapeutic strategy unfeasible. Rather, a substrate-specific approach to targeting is more advantageous, but how OGT chooses its substrates remains poorly understood. Substrate specificity is controlled by the interactions between OGT's non-catalytic tetratricopeptide repeat (TPR) domain, rather than its glycosyltransferase domain. OGT's TPR domain forms a 100 Å superhelical structure, containing a lumenal surface, known as the substrate-binding surface, and a solvent-exposed surface. To date, there are no tools to site-selectively target regions of the domain and differentiate between the two binding surfaces. Here, we developed a library of recombinant OGT constructs containing site-specifically incorporated photoactivatable unnatural amino acids (UAAs) along the solvent-exposed surface of the TPR domain to covalently capture and map OGT's interactome.

Bone microarchitecture evaluated by HR-pQCT in Chinese adolescent and pediatric patients with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Previous studies have found deteriorated bone microarchitecture in the XLH adults. Detailed studies on the skeletal microarchitecture of XLH adolescent and pediatric patients are still lacking. This study aimed to evaluate bone geometry, density, microarchitecture, stiffness in XLH adolescent and pediatric patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT).Method: This study utilized HR-pQCT to assess bone geometry, density, microarchitecture, and stiffness in 106 Chinese adolescent and pediatric patients with XLH. Compared with the sex- and age-matched controls, XLH patients had significantly higher trabecular area (Tb.Ar), lower total volumetric bone mineral density (Tot.vBMD), lower cortical volumetric BMD (Ct.vBMD), and lower stiffness at both the distal radius and the tibia after adjusting for height and weight. Alkaline phosphatase Z score (ALP-Z), a marker to reflect the disease activity of rickets, was negatively correlated with Ct.vBMD and cortical thickness (Ct.Th) at the distal radius, and Ct.vBMD at the distal tibia, and positively correlated with cortical porosity (Ct.Po) at the distal tibia. We developed an online calculator to estimate Tb.Ar, Ct.vBMD, and stiffness of the distal tibia of XLH adolescent and pediatric patients based on clinical general characteristic and biochemical indicators. The bone microarchitecture of XLH adolescent and pediatric patients was deteriorated, and ALP-Z was negatively correlated with the skeletal quality of XLH adolescent and pediatric patients, especially in the cortical bone. HR-pQCT parameters can be estimated using clinical characteristics and biochemical indicators, which may assist physicians to monitor the disease progression in areas without HR-pQCT access.

Assessment of the frequency and risk factors for colorectal cancer in acromegaly.

Acromegaly is associated with a possible increased risk of neoplasias, like colorectal cancer (CRC), although magnitude of this risk is unclear. Evaluate frequency of colonic adenomatous polyps and CRC in patients with acromegaly at first and subsequent colonoscopies; correlate risk factors of CRC and disease activity of acromegaly with colonoscopy findings and analyze relationship of acromegaly as a risk factor for CRC and the best period for screening this neoplasia. Patients ≥18 years-old with acromegaly were included. A questionnaire involving characteristics of follow-up of acromegaly and risk factors of CRC was created. Biochemical and colonoscopic data were collected through medical records. Only full-length colonoscopies with satisfactory colonic preparation were included. 123 patients (77 women) were included (mean age at diagnosis of 43.1 years and mean follow-up of 13.7 years). In baseline colonoscopy, 80.5% had non-neoplastic findings, 14.6% non-advanced adenomas, 3.3% advanced adenomas and 1.6% CRC. At end of the study, 3 (2.4%) patients were diagnosed with CRC. No patient under 50 years had a neoplastic lesion on colonoscopy. We observed a positive statistically significant relationship between smoking (p = 0.026), age at diagnosis of acromegaly (p < 0.001), age at baseline colonoscopy (p = 0.002), and risk of adenomas and/or CRC at initial colonoscopy. Smoking and advanced age were positively related to a higher risk of developing premalignant/malignant colonic lesions. Age ( > 50 years) was the most robust variable. Our data suggest that screening age for CRC in acromegaly should be reviewed.

Epimedium polysaccharides ameliorate ulcerative colitis by inhibiting oxidative stress and regulating autophagy.

Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved. The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression. In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.

Correlation of retinal fluid and photoreceptor and RPE loss in neovascular AMD by automated quantification, a real-world FRB! analysis.

To quantify ellipsoid zone (EZ) loss during anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) and correlate these findings with nAMD disease activity using artificial intelligence-based algorithms. Spectral domain optical coherence tomography (Spectralis, Heidelberg Engineering) images from nAMD treatment-naïve patients from the Fight Retinal Blindness! (FRB!) Registry from Zürich, Switzerland were processed at baseline and over 3 years of follow-up. An approved deep learning algorithm (Fluid Monitor, RetInSight) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). An ensemble U-net deep learning algorithm was used to automated quantify EZ integrity based on EZ layer thickness. The impact of fluid volumes on EZ thickness and late-stages outcomes were calculated using Wilcoxon rank-sum tests, a linear mixed model and a longitudinal panel regression model. Two hundred and eleven eyes from 158 patients were included. The mean ± SD EZ loss area in the central 6 mm was 1.81 ± 2.68 mm2 at baseline and reached 6.21 ± 6.15 mm2 at month 36. Higher fluid volumes (top 25%) of IRF and PED in the central 1 and 6 mm of the macula were significantly associated with more advanced EZ thinning and loss compared to the low fluid volume subgroup. The high SRF subgroup in the linear regression model showed no statistically significant association with EZ integrity in the central macula; however, the longitudinal analysis revealed an increased EZ thickness with no additional loss. Intraretinal fluid and PED volumes and their resolution pattern have an impact on alteration of the underlying EZ layer. AI-supported quantifications are helpful in quantifying early signs of macular atrophy and providing individual risk profiles as a basis for tailored therapies for optimized visual outcomes.

Psychometric evaluation of the Functional Assessment of chronic illness therapy-fatigue (FACIT-Fatigue) in adults with moderately to severely active Crohn's disease.

To provide further evidence on the psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in moderately to severely active Crohn's disease (CD), and to determine thresholds for meaningful improvement in fatigue. The FACIT-Fatigue is a 13-item patient-reported outcome measure (range, 0-52) assessing fatigue over the previous week. Using pooled data from the Phase 3 VIVID-1 study of moderately to severely active CD, psychometric properties of FACIT-Fatigue were evaluated up to Week 52. The Patient Global Rating of Severity (PGRS) and Patient Global Impression of Change (PGIC) were used as primary anchors to estimate the FACIT-Fatigue score change representing meaningful improvement. Psychometric analyses included 1065 adults. The FACIT-Fatigue demonstrated good internal consistency, and correlations between individual items and the total score were moderate to strong. The FACIT-Fatigue score showed moderate to strong correlations with other patient-reported assessments and weak correlations with endoscopic/laboratory assessments. The FACIT-Fatigue differentiated between distinct groups of participants varying in disease severity, quality of life, and fatigue based on PGRS and other assessments. FACIT-Fatigue improvements during the study differed significantly between most PGRS change and PGIC categories. Anchor-based estimates suggested a 6-9-point increase in the FACIT-Fatigue total score as meaningful improvement. The FACIT-Fatigue demonstrated strong psychometric properties in the VIVID-1 population of adults with moderately to severely active CD and determined a FACIT-Fatigue score change threshold representing meaningful improvement. NCT03926130. Registered 23 April 2019, https://clinicaltrials.gov/study/NCT03926130 .

Therapeutic Dose of Zinc Aspartate and Zinc Citrate Attenuates Disease Activity Indices in Rheumatoid Arthritis.

Zinc aspartate and zinc citrate have been used as zinc supplements in different health conditions. Taking into consideration their anti-inflammatory, immunomodulatory, anti-oxidant and antimicrobial properties, the present study has been designed to analyse the effect of zinc aspartate and zinc citrate treatment at therapeutic dose level on disease severity index, haematological, serological, antimicrobial and radiological markers of rheumatoid arthritis in Wistar rats. Bactericidal potential of the two organic zinc compounds was analysed in vitro in clinically isolated Escherichia coli. Arthritis was induced in male Wistar rats by intradermal injection of an emulsion containing collagen type II and Complete Freund's Adjuvant (CFA) containing 1mgmL-1 Mycobacterium tuberculosis H37Ra. Zinc aspartate and zinc citrate were orally administered after the onset of the disease for 4weeks. Ameliorative effect of zinc aspartate and zinc citrate was evaluated by analysing indices of severity and disease activity markers of rheumatoid arthritis. The liver and kidney function tests were performed to evaluate any possible adverse effect of compounds. Antimicrobial activity of the zinc compounds was assessed in clinically isolated E. coli by MTT assay. Zinc aspartate and zinc citrate equivalent to a therapeutic dose of 50mg/day of elemental zinc attenuated the clinical characteristic of rheumatoid arthritis in the animal model of arthritis, collagen-induced arthritis (CIA). Both zinc salts also exhibited antimicrobial effects against E. coli. The selected dose of zinc aspartate and zinc citrate showed no adverse effects in treated rats. This study highlights the potentiality of zinc compounds as antiarthritic agents and also point to its preventive effects on microbial growth that has been observed in rheumatoid arthritis patients due to their increased sensitivity for bacterial infection.

Chronic Spontaneous Urticaria—New Predictor on the Horizon?

Chronic urticaria is one of the most common diseases in allergology and dermatology practice with unclear causes of occurrence. Background: Some studies emphasize the correlation between inflammation in chronic urticaria and disturbed intestinal microbiota. It raises the question about the role of some intestine-related substances in the pathogenesis of urticaria as well as their potential role as disease predictors. Calprotectin is an acute-phase protein with a well-established diagnostic position in the field of gastroenterology. There are some data on the relationship between this parameter and gut microbiota. The major aim of this preliminary study is to investigate whether calprotectin can be potentially taken into account as a disease course predictor in urticaria. Methods: We included in our study 54 chronic spontaneous urticaria (CSU) patients (of whom 26 manifested the symptoms of recurrent angioedema) and 29 patients allergic to Hymenoptera venom for the reference group (in these patients, before venom immunotherapy induction, full diagnostics is performed including intestinal problems). Disease activity in the CSU patients was assessed using the Urticaria Activity Score (UAS) and the disease control in this group was assessed with the Urticaria Control Test (UCT). Moreover, we analyzed fecal and serum calprotectin concentrations. Results: Positive correlation was found only between the values of serum calprotectin concentration and the control level of CSU symptoms with the lack of other relations. Conclusions: Our results do not supply unequivocal evidence for calprotectin as a potential marker of CSU course, though this concept, in the light of growing evidence for microbiota’s role in urticaria, requires further research.

A Small Molecule Antagonist of CX3CR1 (KAND567) Inhibited the Tumor Growth-Promoting Effect of Monocytes in Chronic Lymphocytic Leukemia (CLL)

Background/Objectives: Nurse-like cells (NLCs) derived from monocytes in the tumor microenvironment support the growth of chronic lymphocytic leukemia (CLL) cells. Here, we investigated the effects of a CX3CR1 (fractalkine receptor) antagonist (KAND567) on autologous monocytes and their pro-survival effects on CLL cells in vitro. Methods: Plasma concentration of CX3CL1 was determined by ELISA and CX3CR1 expression by flow cytometry. CD19+ cells and autologous monocytes from patients with CLL and healthy donors were treated with KAND567 either in co-culture or alone. The apoptosis of CD19+ cells and monocytes was determined by Annexin V/PI staining and live-cell imaging. Results: Plasma concentration of CX3CL1 (fractalkine) was significantly higher in patients with CLL (n = 88) than in healthy donors (n = 32) (p &lt; 0.0001), with higher levels in patients with active compared to non-active disease (p &lt; 0.01). CX3CR1 was found on monocytes but not B cells in patients and controls. Levels of intermediate and non-classical CX3CR1+ monocytes were higher in patients with CLL than in controls (p &lt; 0.001), particularly in those with active disease (p &lt; 0.0001). Co-culture experiments revealed that autologous monocytes promoted the survival of both malignant and normal B cells and that KAND567 selectively inhibited the growth of CLL cells in a dose-dependent manner but only in the presence of autologous monocytes (p &lt; 0.05). Additionally, KAND567 inhibited the transition of monocytes to NLCs in CLL (p &lt; 0.05). Conclusions: Our data suggest that the CX3CR1/CX3CL1 axis is activated in CLL and may contribute to the NLC-driven growth-promoting effects of CLL cells. KAND567, which is in clinical trials in other disorders, should also be explored in CLL.

Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China

ObjectivesTo explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE).MethodsThe PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group).ResultsFrom 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; Pnon-inferiority=0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI −0.5% to 13.5%; Pnon-inferiority=0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups.ConclusionsGC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal.Trial registration numberNCT02842814.

Dietary habit and risk of rheumatoid arthritis: a mendelian randomization study identifying protective and risk factors.

Dietary habit significantly contributes to the initiation and progression of rheumatoid arthritis (RA). Dietary choices intersect with a range of clinical and societal factors. The utilization of cross-sectional methodologies in numerous studies poses a challenge in establishing definitive causality for the noted associations. Moreover, within identical food categories, specific items may elicit diverse effects on the pathogenesis of RA, and the correlation between several prevalent food items or beverages and RA remains inadequately explored. We performed a two-sample Mendelian Randomization (MR) study to evaluate the causal impact of 27 distinct dietary habits and RA susceptibility. These dietary-related phenotypes encompass both the relative intake of the four macronutrients (fat, protein, carbohydrates, and sugar) and 23 specific single food intake. Several filtering steps were employed to select eligible genetic instruments strongly associated with each of the traits. The random-effects inverse-variance weighted, weighted median, and MR-Egger methods were employed for MR estimations. Sensitivity analyses and power calculations were executed to ensure the robustness of our study. After rigorous single-nucleotide polymorphism (SNP) filtering procedures, 611 SNPs were included in our ongoing investigations. The consumption of dried fruit, bread, and alcohol emerged as protective factors, while beef, processed meat, and coffee intake were identified as risk factors. The robustness of our study was confirmed through the outcomes of sensitivity analysis and power calculation. The ongoing investigations furnish evidence that accentuates the influence of diet on RA disease activity, underscoring the importance of delineating the optimal nutritional lifestyle for RA patients.