Autoimmune Inflammatory Disease Research Articles

The Association between the Response to Rituximab with Sociodemographic Data and Disease Characteristics Among a Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Rituximab (RTX), a monoclonal antibody with anti-CD20 action, is now used as a treatment. Even with proper RTX use, some patients showed variations in response. Objective: To assess the association of different sociodemographic data and disease characteristics with RTX responsiveness in RA patients. Methods: A cross-sectional study was conducted in the Specialized Center of Rheumatology at Baghdad Teaching Hospital in Baghdad, Iraq. The study included 90 RA patients who received a 1000mg RTX intravenous infusion for at least six months. The collected sociodemographic data included age, gender, smoking status, body mass index (BMI), disease characteristics such as co-morbidities, and the use of previous biological agents. The activity of RA was assessed by the 28-joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI). Results: Upon measuring the DAS28, the enrolled patients were divided into RTX responders (50 patients) and RTX non-responders (40 patients). Patients with a family history of RA were significantly higher in the RTX responders (21% versus 2% in the non-responders group). The responders had a significantly longer RA duration (p=0.030).The mean of CDAI and DAS28 were significantly higher in patients with no family history of RA than in those with a family history of RA. Conclusions: Disease duration, family history, and the use of previous biological agents could be considered as possible predictors of response to RTX, thereby saving time and treatment costs.

Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.

Acute phase reactants

The serum concentrations of certain proteins are altered in various conditions such as infection, trauma, inflammatory arthritis, malignancy, autoimmune and systemic inflammatory diseases. These proteins are known as positive or negative acute phase reactants. While albumin and transferrin belong to the negative acute phase reactants, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, C-reactive protein, ceruloplasmin, haptoglobin, serum amyloid A and fibrinogen are known as positive acute phase reactants. This review discusses the clinical use of C-reactive protein, erythrocyte sedimentation rate and procalcitonin.

Effect of Vitamin D deficiency and some hematological parameters in Iraqi female patients with Systemic Lupus Erythematosus

Background: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects multiple organs. Vitamin D deficiency is considered potential environmental factor triggering some autoimmune disorders, including SLE. This study was performed for determination of effect of vitamin D deficiency in SLE infection or disease worsening, and the relationship of ESR, HB, and WBCs with level of vitamin D in SLE disease, in addition to determine which of the previous parameter may describe the disease case of patients. Methods: This study included fifty three (53) SLE female patients and twenty six (26) healthy females were included. White blood count (WBC) and Heamoglobin (Hb) were determined in complete blood count (CBC) device, traditional Westergren method was used for Erythrocyte sedimentation rate (ESR) estimation, vitamin D was measured by using enzyme link immune-sorbent assay (ELISA) Kit. Results: The results showed a significant decrease in the hemoglobin levels in the SLE patients; significant increase was noticed in the ESR of SLE patients and significant increase was noticed in the WBC counts compared to the control group’s samples. A significant decrease in serum levels of vitamin D in patients compared to apparently healthy controls. Conclusions: Photosensitivity to sun in SLE patients contributed in decrease of vitamin D blood-levels. According to the ROC results, each of Hb, WBC, ESR and vitamin D may describe the disease case of patients.

Association between Helicobacter pylori and its eradication and the development of cancer

BackgroundHelicobacter pylori (H. pylori) is a gram-negative gastrointestinal pathogen that colonises the human stomach and is considered a major risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. Furthermore,...

Application of methylation in the diagnosis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, mainly characterized by perifibrocartilage osteitis of the sacroiliac joints and spinal enthesitis. To date, the exact pathogenesis of AS remains elusive. It is generally believed that AS is a multifactorial disease involving genetics, infection, environment, and immunity. Among them, genetic factors are the primary determinants of disease risk and severity. In recent years, epigenetic mechanisms such as DNA methylation have been extensively surveyed with respect to the pathogenesis of AS. This review summarizes the latest research progress of methylation in AS, from whole-genome sequencing to individual differentially methylated gene. And finally, the role of methylase in AS inflammation, autophagy, and osteogenic differentiation was explored. In summary, the results of this review attempt to explain the role of methylation in the occurrence and development of AS and point out the shortcomings of current methylation research, providing directions for subsequent methylation research in AS.

“Glycans in Trained Immunity: Educators of innate immune memory in homeostasis and disease”

Trained Immunity is defined as a biological process normally induced by exogenous or endogenous insults that triggers epigenetic and metabolic reprogramming events associated with long-term adaptation of innate immune cells. This trained phenotype confers enhanced responsiveness to subsequent triggers, resulting in an innate immune “memory” effect. Trained Immunity, in the past decade, has revealed important benefits for host defense and homeostasis, but can also induce potentially harmful outcomes associated with chronic inflammatory disorders or autoimmune diseases. Interestingly, evidence suggest that the “trainers” prompting trained immunity are frequently glycans structures. In fact, the exposure of different types of glycans at the surface of pathogens is a key driver of the training phenotype, leading to the reprogramming of innate immune cells through the recognition of those glycan-triggers by a variety of glycan-binding proteins (GBPs) expressed by the immune cells. β-glucan or mannose-enriched structures in Candida albicans are some of the examples that highlight the potential of glycans in trained immunity, both in homeostasis and in disease. In this review, we will discuss the relevance of glycans exposed by pathogens in establishing key immunological hubs with glycan-recognizing receptors expressed in immune cells, highlighting how this glycan-GBP network can impact trained immunity. Finally, we discuss the power of glycans and GBPs as potential targets in trained immunity, envisioning potential therapeutic applications.

Synthetic polypeptides inhibit nucleic acid-induced inflammation in autoimmune diseases by disrupting multivalent TLR9 binding to LL37-DNA bundles.

Complexes of extracellular nucleic acids (NAs) with endogenous proteins or peptides, such as LL37, break immune balance and cause autoimmune diseases, whereas NAs with arginine-enriched peptides do not. Inspired by this, we synthesize a polyarginine nanoparticle PEG-TK-NPArg, which effectively inhibits Toll-like receptor-9 (TLR9) activation, in contrast to LL37. To explore the discrepancy effect of PEG-TK-NPArg and LL37, we evaluate the periodic structure of PEG-TK-NPArg-NA and LL37-NA complexes using small-angle X-ray scattering. LL37-NA complexes have a larger inter-NA spacing that accommodates TLR9, while the inter-NA spacing in PEG-TK-NPArg-NA complexes mismatches with the cavity of TLR9, thus inhibiting an interaction with multiple TLR9s, limiting their clustering and damping immune induction. Subsequently, the inhibitory inflammation effect of PEG-TK-NPArg is proved in an animal model of rheumatoid arthritis. This work on how the scavenger-NA complexes inhibit the immune response may facilitate proof-of-concept research translating to clinical application.

Unravelling the Significance of NLRP3 and IL-β1 in Oral Squamous Cell Carcinoma and Potentially Malignant Oral Disorders: A Diagnostic and Prognostic Exploration.

Nucleotide-binding domain-like receptor protein 3 (NLRP3), an inflammasome, is reported to be dysregulated or aberrantly expressed in chronic inflammation, leading to a myriad of inflammatory disorders, autoimmune diseases, and cancer. This study aimed to explore the expression and role of NLRP3 protein and the secreted cytokine IL-β1 in oral squamous cell carcinoma (OSCC) and potentially malignant oral disorders (PMOD). Tissue NLRP3 expression was quantified using sandwich ELISA in 30 cases each of OSCC, PMOD, and normal oral mucosa. Serum IL-β1 level was also measured by ELISA to determine their correlation. In surgically treated OSCC cases, pathological parameters such as tumor size, depth of invasion (DOI), pTNM stage, and perineural & lymphovascular invasion were assessed and correlated with NLRP3 & IL-β1 levels to investigate their roles in tumor progression, invasion, and metastasis. Tissue NLRP3 expression was markedly elevated in OSCC, with significant IL-β1 levels observed in the serum of both OSCC and PMOD cases. Both markers showed a pronounced increase with the severity of dysplasia, indicating a strong association (p = 0.003%). The expression levels of tissue NLRP3 and serum IL-β1 were positively correlated with DOI and tumor size. Furthermore, their elevated levels, alongside higher histological grades, indicate roles in the dedifferentiation and progression of tumor cells. The findings indicated that increased expression of NLRP3 and IL-β1 in PMOD correlates with higher transformation rates, along with tumor progression and dedifferentiation in OSCC. Consequently, these markers hold promise as valuable targets for prognostic assessment, diagnostics, and therapeutic strategies in OSCC.

Clinical outcomes and risk factors in patients with COVID-19 and autoimmune rheumatic diseases: insights from a major Australian hospital study.

Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID-19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccine status, were associated with more severe forms of COVID-19 infection. Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID-19 infection were analysed using a binary regression model and a multinomial regression model. The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35-25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21-23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63-19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05-0.69) and three and four doses (OR = 0.09; 95% CI = 0.02-0.35) were all statistically significant factors related to changes in the severity level of COVID-19. Severity of COVID-19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID-19 severity.

Therapeutic potential of Nelumbo nucifera Linn. in systemic lupus erythematosus: Network pharmacology and molecular modeling insights.

Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study. Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study. In total, 12 active compounds and 1190 targets of N. nucifera's were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than -4.5kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex's stability and flexibility. Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.

Ocular Adverse Effects of TNF-α Inhibitors in the FDA Adverse Event Reporting System (FAERS)

Autoimmune inflammatory diseases affect 7.6-9.4% of the global population, predominantly women. TNF-α inhibitors (TNFI) have revolutionized rheumatic disease treatment but are associated with serious ocular adverse events (AEs). We analyzed FAERS data for adalimumab, etanercept, and infliximab (1998-2024), documenting patient demographics and the top 10 ocular AEs for each TNFI. Of the 45,445 reported ocular AEs, 66.6% were in females and 50.3% were in adults aged 18-64. The most common AEs included visual impairment (7,093), cataract (5,730), and blurred vision (5,586). There were 2,271 reports of blindness. The distribution of AEs was similar across adult age groups but rare in pediatric patients and those over 85. A review by da Silva et al corroborates our findings, identifying uveitis, optic neuropathy, and retinal toxicity among others. FAERS data showed 1,927 uveitis cases linked to adalimumab, 1,054 to etanercept, and 1,076 to infliximab. These AEs may result from TNF-α binding in ocular tissues, paradoxically causing and treating uveitis. Our study highlights the severity of ocular AEs with TNFI use, suggesting a need for vigilance in monitoring patients, especially given the potential for irreversible blindness. The limitations include voluntary reporting and underreporting in FAERS, underscoring the need for further research to better understand these risks.

Intra-Articular Delivery of an AAV-Anti-TNF-α Vector Alleviates the Progress of Arthritis in a RA Mouse Model.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor necrosis factor (TNF) plays a critical role in RA pathogenesis. Although TNF-targeting drugs are clinically effective, their need for frequent and long-term administration often results in poor patient adherence and suboptimal outcomes. This study developed a gene therapy approach using engineered adeno-associated virus (AAV) vectors to deliver an anti-TNF agent directly into the joint cavity of RA animal models. Animals receiving this therapy demonstrated sustained improvement in clinical scores, inflammatory markers, and joint tissue health. Immunofluorescence staining revealed that AAV vectors could transduce various cell types, including T cells, type A synoviocytes, and dendritic cells. Our results indicate that a single administration of this gene therapy provided long-term efficacy. This suggests that AAV-mediated anti-TNF gene therapy can offer prolonged relief from clinical symptoms and reduce inflammatory damage in a mouse model of RA. This innovative approach presents a promising new therapy with significant clinical prospects to treat patients with RA.

ОТНОШЕНИЕ К ВАКЦИНАЦИИ ДЕТСКИХ ГАСТРОЭНТЕРОЛОГОВ И РЕВМАТОЛОГОВ ПО РЕЗУЛЬТАТАМ АНОНИМНОГО ОНЛАЙН-ОПРОСА

Vaccination of patients with immune-mediated diseases, such as inflammatory bowel diseases (IBD) and juvenile idiopathic arthritis (JIA), is an actual problem since these patients have an increased risk of developing infectious complications due to immunosuppressive therapy and features of the disease itself. The specialists’ attitude towards vaccination of patients with autoimmune inflammatory diseases has changed dramatically over the past decades: from complete refusal previously to almost complete implementation of the vaccine complex and the use of vaccines outside the national immunization schedule as of now. The purpose of this research was to assess the current attitude of pediatric gastroenterologists (PGs) and rheumatologists (PRs) towards vaccination of patients with IBD and JIA, to study their levels of knowledge and practical skills in this area using the anonymous online survey. Materials and methods used: an anonymous survey of 97 pediatric practitioners was conducted, of which 51 were PGs and 46 PRs. The questionnaire included questions about the physicians’ themselves (gender, experience, facility, academic degree) and their knowledge and approaches to vaccination of patients with IBD and JIA with live and inactivated vaccines during different stages of therapy. Results: most physicians believed that immune-inflammatory diseases are not provoked by vaccination (88% of PGs and 69.6% of PRs). A significant group of physicians (40.3% of PGs and 36.9% of PRs) consider vaccination with live vaccines safe for patients with IBD/JIA in remission while receiving immunosuppressive therapy. Most physicians consider vaccination with live vaccines unsafe in the state of active disease (80.4% of PGs and 71.8% of PRs). Outside of remission, physicians vaccinate such patients with live vaccines extremely rarely. A significant portion of physicians (32.0% of PGs and 21.7% of PRs) do not participate in vaccination considering it the responsibility of primary care pediatric practitioners/family physicians. Still, a significant portion of physicians (18.0% of PGs and 47.8% of PRs) actively discourage vaccination in general during the treatment of an immune-inflammatory disease. Determining antibodies to vaccines before starting immunosuppressive therapy/vaccination is considered appropriate by only 35.2%/47.0% of PGs and 32.5%/67.3% of PRs (р=0,885/0,110, respectively). Some physicians believe that vaccination can provoke an exacerbation of IBD/JIA (13.7%/21.6% of PGs and 21.7%/34.8% of PRs answered in affirmative or “rather yes than no,” respectively). Conclusion: the study revealed a differentiated attitude towards vaccination issues between PGs and PRs. Additional efforts needed in order to change the attitude of physicians of different specialties towards vaccination.

Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance

The mechanisms of endotoxin tolerance (ET), which down-regulate inflammation, are well described in response to exogenous toll-like receptor ligands, but few studies have focused on ET-associated mechanisms in inflammatory disease. As blocking TNF can attenuate the development of ET, the effect of anti-TNF on the expression of key ET-associated molecules in inflammatory auto-immune disease was measured; changes in inflammatory gene expression were confirmed using an ET bioassay. The expression of immunomodulatory molecules was measured in a murine model of arthritis treated with anti-TNF and the expression of ET-associated molecules was measured in whole blood in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients, before and after therapy. The expression of ET-associated genes was also measured in RA patient monocytes before and after therapy, in anti-TNF responders and non-responders. Tnfaip3, Ptpn6 and Irak3 were differentially expressed in affected paws, spleens, lymph nodes and circulating leucocytes in experimental murine arthritis treated with anti-TNF. Prior to therapy, the expression of TNFAIP3, INPP5D, PTPN6, CD38 and SIGIRR in whole blood differed between human healthy controls and RA or AS patients. In blood monocytes from RA patients, the expression of TNFAIP3 was significantly reduced by anti-TNF therapy in non-responders. Prior to therapy, anti-TNF non-responders had higher expression of TNFAIP3 and SLPI, compared to responders. Although the expression of TNFAIP3 was significantly higher in RA non-responders prior to treatment, the post-treatment reduction to a level similar to responders did not coincide with a clinical response to therapy.

Role of diffusion tensor imaging of extra ocular muscles and orbital fat in Graves’s ophthalmopathy and relation to disease activity

BackgroundGraves’ ophthalmopathy (GO) is one of the most common autoimmune inflammatory disorders affecting the orbit that characterized by swelling of extra ocular muscles (EOMs) and expansion of the orbital fat. Diffusion tensor imaging (DTI) could assess the microstructural integrity of tissue. We aimed at this study to assess the role of DTI in the evaluation of EOMs and orbital fat in GO and identify the relationship with disease activity.ResultsCase–control study included 40 patients diagnosed as Graves’ disease (20 active and 20 inactive) and 10 health control subjects underwent DTI. Low fraction anisotropy (FA) and high mean diffusivity (MD) of inferior rectus (IR), medial rectus (MR) and orbital fat in GO versus healthy control (HC), while high FA and high MD in active group versus inactive group. In order to differentiate between GO and HC; FA cutoff point of IR, MR& orbital fat were 0.46, 0.45 and 0.26 with sensitivity 98.8%,98.8% and 93.8% and specificity 95.0%, 95.0% and 85%, respectively. MD cutoff point for IR, MR and orbital fat 1.24, 1.27 and 1.275 with sensitivity 97.5%, 98.8% and 98.8% and specificity 95.0%, 95% and 95%, respectively. To differentiate between active and inactive GO; FA cutoff point of IR, MR and orbital fat were 0.35, 0.36 and 0.22 respectively with sensitivity 80.0%, 82.5% and 72.5% and specificity 95.0%, 85.0% and 65.0%, respectively. MD cutoff point for IR, MR and orbital fat were 1.58, 1.63 and 1.54 respectively with sensitivity 90.0%, 97.5% and 85.0%, and specificity 90.0%, 80.0% and 62.5%, respectively.ConclusionsDTI parameters (FA and MD) of EOMs and orbital fat are considered as crucial radiological biomarkers for diagnosis of GO and could quantitatively differentiate active form inactive disease.

Relationship between Oral Lichen Planus and Cardiovascular Disease of Atherosclerotic Origin: Systematic Review and Meta-Analysis.

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory autoimmune disease of the oral mucosa that affects between 0.5% and 2% of the general population. In the last decade, several studies have associated cardiovascular diseases (CVDs) with some inflammatory skin diseases such as oral lichen planus, demonstrating the presence of dyslipidemia in these pathologies. The objective of this work is to review whether patients with OLP show higher dyslipidemia and CRP levels compared to a healthy control population without OLP. Methods: Searches were carried out in Medline, Scopus, and Cochrane. The studies had to perform a histopathological diagnosis for OLP and the patients could not take any medication to treat this disorder. Non-lichenoid reactions were included. Results: After an initial search that provided us with 254 papers, this number was reduced to 10 articles after a detailed evaluation. All of them were case-control studies that compared the presence of analytical cardiovascular risk factors in patients affected by OLP and in healthy subjects. Conclusions: There is no scientific evidence of the possible association between OLP and CVDs. The only association we can prove is the one between OPL and CVD risk factors, especially those related to the lipid profile. More studies are needed in order to evaluate this relationship in patients diagnosed with CVDs.

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

Targeting toll-like receptor 7 as a therapeutic development strategy for systemic lupus erythematosus

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives’ inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

The Association of Anti-CCP Positivity with Extra-Articular Manifestations in Patients with Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disorder that primarily affects the joints. Objective: To examine association between anti-cyclic citrullinated peptide and extra-articular manifestation of Rheumatoid arthritis. Methods: It was a descriptive cross-sectional study in the Department of Rheumatology outpatient Khyber Teaching Hospital in Peshawar from 13th April 2023 to 13th September 2023. A descriptive cross-sectional study was conducted on 100 patients diagnosed with rheumatoid arthritis according to ACR/EULAR 2010 criteria at the Rheumatology outpatient department of Khyber teaching hospital in Peshawar from 13th April 2023 to 13th September 2023. Sampling technique was non probability consecutive. Statistical analysis was performed using SPSS version 23.0. Results: Our study involved 100 patients diagnosed with rheumatoid arthritis. Majority of the patients were female (90%) with overall mean age was 42.3 ± 10.06 years. The average duration of the disease was 5.9 years, with a mean RA disease activity score of 2.8. Extra-articular manifestations were observed in 84% of the patients, encompassing various symptoms such as anemia, subcutaneous nodules, episcleritis, and interstitial lung disease. Most patients (94%) tested positive for Rheumatoid Arthritis Factor, while 84% tested positive for anti-CCP antibodies. Our analysis revealed significant associations between the presence of extra-articular manifestations and factors such gender distribution, disease activity score and anti-CCP antibody positivity while no significance was noted for factors such as age, Rheumatoid Arthritis Factor and duration of disease. Conclusions: Our study concludes that anti-CCP was positively associated with the presence of extra-articular manifestation of Rheumatoid Arthritis.