TNF-α Inhibitors Research Articles

Pulmonary toxicity assessment of tumor necrosis factor α inhibitors in the treatment of IBD: a real world study based on US food and drug administration adverse events reporting system (FAERS).

Tumor necrosis factor α (TNF-α) inhibitors are widely used in the treatment of inflammatory bowel disease (IBD), but there is still a lack of systematic risk assessment for pulmonary toxicity. We calculated the pulmonary-related risk signals for four TNF-α inhibitors using the disproportionality analysis and also compared them with the pulmonary-related signals of seven other therapies. There were 8736 reports of pulmonary-related adverse events (AEs) to TNF-α inhibitors as the 'primary suspect (PS)' therapies. The median time to incident for pulmonary-related AEs was 148 (interquartile range [IQR] 21-721) days. TNF-α inhibitors exhibited the strongest signal of pulmonary toxicity compared to Interleukin 12/23 (IL-12/23) inhibitors, Integrin blockers, Jak inhibitors, and S1P receptor modulator. Golimumab exhibited the strongest signal compared to infliximab, certolizumab pegol, and adalimumab. The strongest signal corresponding to pneumonia, pulmonary tuberculosis, asthma, chronic obstructive pulmonary disease (COPD), pulmonary thrombosis, and pulmonary fibrosis is golimumab, infliximab, infliximab, natalizumab, upadacitinib, and adalimumab. TNF-α inhibitors had the strongest signal of pulmonary toxicity relative to other control therapies. Golimumab had the strongest signal of pulmonary toxicity relative to other TNF-α inhibitors. When TNF-α inhibitors are used in the treatment of IBD, pulmonary-related AEs should be vigilant.

Adalimumab Use in Severe Recalcitrant Vulval Lichen Sclerosus and Vulval Lichen Planus.

This case series aims to evaluate the demographic features, disease characteristics, and treatment outcomes of 8 patients receiving subcutaneous (SC) adalimumab for severe, refractory vulval lichen sclerosus (VLS) and/or vulval lichen planus (VLP). Both conditions are chronic inflammatory dermatoses that significantly impair quality of life, and although first-line treatment typically involves potent to ultrapotent topical corticosteroids, managing severe cases is challenging due to a lack of FDA-approved systemic therapies. Adalimumab, a TNF-α inhibitor, may offer a promising alternative by targeting the inflammatory cytokine implicated in the pathogenesis of both conditions. Eight patients received SC adalimumab for VLS and/or VLP at a tertiary referral vulvar disorders clinic from September 2020 to June 2024. Among the 8 patients, 4 had VLS/VLP clinical overlap, 2 had VLP, and 2 had VLS. Evaluation included patient-reported outcome measures (PROMs) namely the vulval life quality index (VLQI) and numerical rating scales for itch and pain, and objective clinical severity was assessed by a vulvar dermatologist based on cutaneous signs and architectural features. Adalimumab was well tolerated by 6 of 8 patients who received treatment for at least 9 months. Varying degrees of clinical improvement were observed in cutaneous signs and PROMs, including significant reductions in vulval life quality index scores for 6 patients. Architectural changes remained stable throughout treatment for all patients. This case series indicates that SC adalimumab may be a treatment option for patients with severe, refractory VLS and VLP, as demonstrated by significant improvements in PROMs. The observed clinical benefits suggest that adalimumab targets key inflammatory pathways in these conditions. Controlled trials are necessary to further validate these findings and define adalimumab's role in managing severe refractory VLS and VLP. Future research should also investigate long-term efficacy and safety, as well as potential predictors of treatment response, to optimize care for this challenging patient population.

Metformin Induced Lichenoïd Drug Eruption

Cutaneous lichenoid drug eruptions are rare adverse drug reactions reminiscent of lichen planus. The most frequently reported culprit drugs are Checkpoint inhibitors, tyrosine kinase inhibitors and TNF-α inhibitors, but other drugs can also be responsible. This case-report is about a 49-year-old woman with a history of type 2 diabetes. She started taking metformin 160 weeks before the onset of a pruritic lichenoid rash on the trunk and limbs, of which the histopathology was in favor of an adverse cutaneous lichenoid drug eruption caracterized by the presence of eosinophilic polynuclei in the perivascular infiltrate. The patient benefited from oral corticosteroids with discontinuation of metformin which resulted in the resumption of the lichenoid rash.

Behçet's disease: incidence, prevalence, and real-word data on the use of biologic agents in Japan.

Behçet's disease (BD) is an autoinflammatory disease that can affect multiple organs, including the gastrointestinal tract. Conventional management comprises anti-inflammatory drugs such as glucocorticoids (GCs) and/or immunomodulators that alleviate symptoms. The introduction of biological agents that target tumor necrosis factorα (TNF-α) has improved disease management. The goal of this work was to analyze the current prevalence and incidence of total BD and gastrointestinal Behçet's disease (GIBD) in Japan, and examine treatment trends, especially regarding the use of TNF-α inhibitors (TNFαi). We performed a retrospective descriptive observational study in which BD and GIBD demographic trends, medical treatment patterns, and reported adverse events (AEs) were assessed among patients with data recorded between 2017 and 2021 in the Japan Medical Data Center Claims Database (now JMDC Inc.). Prevalence of BD and GIBD in Japan during the observation period increased at an annual rate of + 3% and + 4%, respectively, while incidence decreased by - 5% and - 2%, with a more prominent decline in confirmed GIBD cases (- 15%). Although GCs were the most common initial treatment administered, use of TNFαi for BD and GIBD management increased by + 5.6% and + 8.1%, respectively. Severe AEs (mainly pneumonia and GI-associated AEs) were reported in 40% of patients receiving TNFαi; however, a high retention rate (of up to 80%) was observed 3years after treatment initiation. The use of TNFαi for GIBD treatment has increased in Japan in recent years. Additional research is necessary to further evaluate TNFαi effectiveness in GIBD and other BD subtypes.

Psoriatic erythroderma and the efficacy of the IL-23 inhibitor guselkumab in clinical practice

Psoriatic erythroderma is the most severe and rare form of psoriasis, with damage to at least 90 % of the body surface area. Most often, psoriatic erythroderma develops in patients with uncontrolled psoriasis and without timely treatment becomes a potentially life-threatening condition. Against the background of generalized damage to the skin, there is a high risk of developing systemic disorders, and therefore effective and safe treatment methods are needed. Traditional systemic drugs such as retinoids, cyclosporine and methotrexate are not effective and safe enough for psoriatic erythroderma, and in most cases have contraindications associated with comorbid conditions. Systemic genetically engineered biological drugs, including TNF-a inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-23 inhibitors show high efficacy and safety in vulgar psoriasis, which makes it possible to use them in psoriatic erythroderma. However, studies and publications regarding the appointment of systemic biological therapy in psoriatic erythroderma are isolated despite the fact that this is a severe, albeit rare form of psoriasis. Data on the use, as well as the efficacy and safety of the IL-23 inhibitor guselkumab in psoriatic erythroderma are limited. In this article we discuss the clinical manifestations of psoriatic erythroderma, the impact on the quality of life of patients and, using clinical cases as an example, the efficacy and safety of genetically engineered biological therapy with an IL-23 inhibitor (guselkumab) for psoriatic erythroderma are shown.

P128 Florid psoriasis in a patient with psoriatic arthritis and hidradenitis suppurativa: therapeutic challenges

Abstract Hidradenitis suppurativa is a chronic inflammatory disorder that affects the skin. It causes recurring inflammatory lesions which may leave permanent scarring. The disease may be autoinflammatory. Hidradenitis suppurativa has been reported to emerge in patients with spondylarthritis, such as ankylosing spondylitis or psoriatic arthritis. The aim was to describe the case of a male patient who had psoriatic arthritis and developed hidradenitis suppurativa. A patient, male, aged 47 presented with psoriatic arthritis. He was on treatment with a TNFa inhibitor with good response as far as the arthritis was concerned. At the age of 51 he developed hidradenitis suppurativa with lesions in the axillary region bilaterally and under the lower ­mandible. Adalimumab was administered with partial remission of both psoriatic arthritis and hidradenitis suppurativa. However, as psoriatic arthritis was active in the axial skeleton with florid psoriasis and sacroiliitis was present bilaterally secukinumab 150 mg/month was initiated. Thereafter the dose of secukinumab was increased to 300 mg/month. Hidradenitis suppurativa lesions improved significantly. However, the pain in the axial skeleton remained intense. Hidradenitis suppurativa is a chronic inflammatory condition, which may be autoinflammatory in its pathogenesis. Hidradenitis suppurativa may appear in patients with spondylarthritis or psoriatic arthritis. Biologic agents are now applied in the management of hidradenitis suppurativa and appear to be effective. We describe the case of a patient with psoriatic arthritis and hidradenitis suppurativa who was treated effectively with biologic agents. The application of biologic agents in the treatment of hidradenitis suppurativa may shed light on the pathogenesis of the disease.

TNF-α Suppression Attenuates Limbal Stem Cell Damage in Ocular Injury.

Ocular chemical injuries often cause uveal inflammation, upregulation of TNF-α at the limbus, and subsequent limbal stem cell (LSC) damage. In this study, we investigate the protective role of TNF-α suppression in LSC survival. Corneal alkali injuries were performed using NaOH as previously described by our group. Anterior chamber pH elevation in the absence of corneal alkali exposure was achieved by cannulation. A CX3CR1+/EGFP::CCR2+/RFP bone marrow chimera was used to study the role of innate immune cells in LSC damage, which was assessed by TUNEL assay, ABCB5, cytokeratin 12 and 13 staining, flow cytometry, in situ hybridization, and qPCR. Corneal neovascularization and conjunctivalization were evaluated by light microscopy. Intraperitoneal injection of 6.25 mg/kg infliximab was administered after irrigation. A TNFR1/2 knockout mouse was used to confirm the findings by a second method. Systemic administration of 6.25 mg/kg infliximab suppressed uveal inflammation after anterior chamber pH elevation or corneal alkali injury and led to reduction of TNF-α secreting CCR2+ and CX3CR1+ monocytes in the basal limbal tissue. In turn, this led to LSC survival (P < 0.01) and allowed reestablishment of K12+ epithelium (P < 0.05) on the injured cornea. Moreover, it led to less corneal neovascularization, conjunctivalization, and scarring, as compared with untreated animals. The protective effect of TNF-α suppression was confirmed in TNFR1/2 knockout mice. Prompt systemic administration of TNF-α inhibitor prevents LSC deficiency and facilitates corneal reepithelialization after alkali burn. TNF-α suppression may benefit the outcomes of other ocular injuries that cause LSC deficiency.

NADPH oxidase expression profile and PBMC immunophenotypic changes in anti-TNF-treated rheumatoid arthritis patients

The aim of this research was to prospectively evaluate the impact of NOX2 gene expression profile (including NCF1, NCF2 and NCF4 genes) in peripheral blood mononuclear cells (PBMCs) on immune signatures, clinical characteristics and responsiveness to anti-TNFα treatment in RA patients. Blood specimens were collected from 31 rheumatoid arthritis (RA) patients and 25 healthy controls, and 16 RA patients were followed at two timepoints during anti-TNF treatment. mRNA expression levels of selected genes and immunoregulatory cytokines concentrations were determined. We observed the significant upregulation of NCF4 and CD14 expression in RA group. The mRNA levels of NCF1 and CD14 positively correlated both in groups of RA patients and healthy controls. NOX2 gene expression profile was not associated with anti-TNFα responsiveness, nor with RA clinical features. TNFα inhibition has not influenced NOX2 expression either. Notably, this study indicate the novel links between expression levels of NCF1 and monocyte differentiation antigen CD14.

Pickering high internal phase emulsions stabilized by soy protein isolate/κ-carrageenan complex for enhanced stability, bioavailability, and absorption mechanisms of nobiletin

Nobiletin (NOB), a lipid-soluble polymethoxyflavone with potent antioxidant, antimicrobial, and anti-inflammatory properties, suffers from poor stability and pH sensitivity, limiting its bioavailability. In this study, Pickering high internal phase emulsions (HIPEs) stabilized by soy protein isolate (SPI) and κ-carrageenan (KC) were developed to encapsulate and protect NOB. The emulsions, containing a 75 % medium-chain triglyceride (MCT) volume fraction, were optimized by investigating the effects of pH and KC concentration on the key properties such as the creaming index, particle size, zeta potential, microstructure, and rheology. Results showed that under optimal conditions (pH 7 and 1.0 % KC), the SPI/KC HIPEs exhibited improved physicochemical properties. Furthermore, encapsulation of NOB in HIPEs significantly improved its stability against UV exposure, heat, and storage conditions. Additionally, simulated gastrointestinal digestion studies revealed that the SPI/KC HIPEs improved the digestion stability and bioaccessibility of NOB, with controlled release in the intestinal phase. Moreover, the SPI/KC HIPEs facilitated increased cellular uptake and bioavailability of NOB, with clathrin-mediated endocytosis and macropinocytosis as primary absorption pathways. The encapsulated NOB also showed enhanced inhibition of inflammatory markers, including NO, IL-6, and TNF-α. These findings suggested that SPI/KC HIPEs provided a promising delivery system for improving the bioavailability and bioactivity of hydrophobic compounds.

Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis.

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/ IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigen-B27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Reply to 'TNF-α inhibitors and preeclampsia: assessing the evidence for risk reduction'.

Reply to 'TNF-α inhibitors and preeclampsia: assessing the evidence for risk reduction'.

Chronic inflammation deters natural killer cell fitness and cytotoxicity in myeloid leukemia

AbstractNatural killer (NK) cells play an integral role in immunosurveillance against myeloid malignancies, with their mature phenotype and abundance linked to prolonged treatment-free remission in chronic myeloid leukemia (CML). However, NK cell function is suppressed during the disease, and the orchestrators of this impairment are not fully understood. Using a chimeric BCR::ABL1+ CML mouse model, we characterized the impact of the leukemic microenvironment on NK cell function. We showed that NK cells have reduced counts, immature phenotype, poor cytotoxicity, and altered expression of activating and inhibitory receptors in CML mice, which revert to a steady state upon BCR::ABL1 inhibition. Single-cell RNA sequencing revealed an inflammatory cytokine response in CML-exposed NK cells, highlighted by the tumor necrosis factor α (TNFα)-induced gene signature, upregulation of TNFα receptor 2, and enrichment of SOCS family genes such as Cish, the critical NK cell checkpoint. Ex vivo exposure of healthy NK cells to leukemic soluble factors compromised target-specific NK cell degranulation, which was partially rescued by targeting Cish or TNFα. In alignment with these findings, NK cells from healthy donors displayed suppressed cytotoxicity when exposed to plasma from untreated patients with CML, with a partial restoration upon Cish or TNFα inhibition. Furthermore, NK cells from newly diagnosed patients with CML predestined for blast crisis showed an enrichment of the TNFα-induced proinflammatory gene signature identified in CML mice. These results suggest that targeting inflammatory signaling could enhance NK cell-based immunotherapies for CML.

Clinical use of tumor necrosis factor-alpha inhibitors in Iraq: a review of their documented efficacy, safety, and associated genetics

This comprehensive review examines the efficacy and safety of tumor necrosis factor-alpha (TNF-α) inhibitors in treating various autoimmune diseases, and focuses on their application in Iraqi patients. Elevated TNF-α levels are linked to autoimmune disorders, leading to the development of anti-TNF-α therapies such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab, which have gained FDA approval for conditions like psoriasis, in¬flammatory bowel disease, ankylosing spondylitis, and rheumatoid arthritis. While these therapies demonstrate sig¬nificant therapeutic benefits, including improved quality of life and disease management, they also carry risks, such as increased susceptibility to infections and potential malignancies. The review highlights the variable patient re¬sponses to TNF-α inhibitors, influenced by pharmacokinetic and pharmacodynamic factors as well as genetic varia¬tions. The rise of anti-drug antibodies and inadequate drug concentrations are common challenges observed, empha¬sizing the need for therapeutic drug monitoring. Safety profiles of TNF-α inhibitors are generally favorable, but adverse effects (including infections and infusion reactions) have been reported. Genetic factors, such as polymorphisms in the TNF-α gene, may also play a role in the treatment responsiveness and adverse effects, suggesting the potential for personalized medicine approaches. While TNF-α inhibitors effectively manage autoimmune diseases in Iraqi pa¬tients, further research is warranted in order to optimize treatment strategies, assess long-term safety, and explore genetic influences on therapy outcomes. The findings underscore the importance of individualized treatment plans so as to enhance the efficacy and minimize the risks associated with these biologic therapies.

Impact of adalimumab on erectile dysfunction, sperm parameters and hormonal profile in male psoriasis patients: a six-month observational study.

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18-50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes.

Spiro-fused indoline-quinazoline hybrids as smart bombs against TNF-α-mediated inflammation

Inflammation is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity. Anti-inflammatory activity against TNF-α was confirmed in-vivo for all synthesized analogues, with 4b, 4e, 4k, and 4n emerging as the top candidates. Further studies on these four compounds assessed their analgesic effects, as well as their impact on PGE2, NF-κB, paw thickness, and paw weight. In-vitro analyses revealed nanomolar TNFR2-TNF-α binding inhibition for the four leads. Safety evaluations included histopathology, ulcerogenic potential, kidney and liver functions, and acute hemotoxicity. In-silico studies examined drug-likeness, pharmacokinetics, and TNF-α dimer interactions. These results suggest that the four lead compounds possess promising profiles compared to standard therapies.

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies.

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF-α and IL-6 by 75.22% and 82.51%, respectively. It elevated the caspase-3 level by 7.21-fold. Furthermore, IC50 against COX-I, COX-II, and VEGFR-2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

Efficacy of Infliximab in Experimental Tracheal Stenosis.

This study aimed to investigate the efficacy of infliximab, a TNF-α inhibitor, on epithelial damage, inflammation, and fibrosis in experimental tracheal stenosis. Rats were divided into 3 groups. In group 1 (the control group), no procedure was applied. Tracheotomy was opened in the other groups. The laryngotracheal mucosa of the rats was traumatized with a brush through the tracheostoma to create a stenosis model. After surgery, group 2 (the infliximab group) received 5mg/kg infliximab intraperitoneally. In group 3 (the sham group) only 0.5ml of saline (0.9% NaCl) was administered intraperitoneally. After 14 days, the rats were sacrificed. Tracheal rings were excised, and epithelial damage, inflammation, and fibrosis were evaluated histopathologically. Infliximab reduced the formation of epithelial damage (P=0.002), fibrosis (P=0.001), and inflammation (P=0.003) compared with the sham and control group. This was the first investigation displaying the effects of infliximab on tracheal stenosis. The authors' experimental results may offer guidance for further studies. Their experience presents novel sights into optimizing outcomes in tracheal stenosis surgery, and so paves the way for further clinical examinations.

Adalimumab induced CNS demyelination in a patient with multiple pre-existing autoimmune diseases; treatment contemplation.

Anti-TNF agents like Adalimumab are safe and effective for rheumatologic disorders, but they have been reported to cause demyelinating diseases like Multiple Sclerosis (MS). A 47-year-old woman with left hand weakness was evaluated. She had a previous medical history of Intermediate Uveitis (IU) and Rheumatoid arthritis (RA). anti-TNF-α treatment was initiated with adalimumab two years before this visit. MRI showed numerous T2-hyperintense lesions in bilateral periventricular, juxtacortical, and subcortical areas, which were absent in her scan before anti-TNF therapy. She was diagnosed with MS, and Adalimumab was discontinued. IV glucocorticoids (GCs) were administered with marked improvement. She was then started on anti-CD20 therapy with Rituximab. A year later, she was symptom-free, and her follow-up Brain MRI showed no new lesions. The link between MS and TNF-α inhibitors is poorly understood, but several hypotheses have been proposed. Discontinuing anti-TNF therapy alone may not be enough to prevent further demyelinating disease activity, and it is essential to consider the necessity of starting a disease-modifying treatment. Autoimmunity plays a significant role in rheumatologic and neurological diseases, and as personalized medicine advances, understanding genetic risk is crucial for selecting appropriate therapeutic targets. A thorough evaluation of a patient's family background is recommended before therapeutic decision-making, especially in patients with multiple autoimmune disorders, and the question of whether TNF-α is a suitable therapeutic target in patients with multiple autoimmune disorders is raised.

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia

Colorectal cancer (CRC) ranks as China’s second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

Adalimumab Treatment Effects on Inflammation and Adipose Tissue Mitochondrial Respiration in Hidradenitis Suppurativa.

Tumour necrosis factor (TNF)-α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF-α inhibitor. We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)-1β, IL-6, IL-10, high-sensitivity C-reactive protein (hsCRP), interferon-γ, TNF-α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed. We found a higher anti-inflammatory macrophage content (CD206+) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL-6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores. Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti-inflammatory macrophages in the patient group compared with the control group.