Autoimmune Diseases Research Articles

Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus , Ruminococcus , Bacteroides , Bifidobacterium , Escherichia coli , Akkermansia muciniphila , Firmicutes (including Clostridium and Lactobacillus ), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile , Salmonella , Helicobacter pylori , and Fusobacterium nucleatum , are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis , contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota’s role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Acute spontaneous hemorrhagic cholecystitis with systemic lupus erythematosus and antiphospholipid antibody syndrome: a case report and literature review

Introduction and importance: Hemorrhagic cholecystitis (HC) is a rare and serious complication of acute cholecystitis, characterized by intraluminal or extraluminal bleeding within the gallbladder. While commonly associated to gallstones, HC may also arise from coagulopathies, anticoagulant therapy, and autoimmune conditions such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). However, HC in patients with SLE or APS is rarely reported in the literature. Case presentation: A 59-year-old female with a history of SLE and APS, on corticosteroids, hydroxychloroquine, methotrexate, and warfarin, presented with acute right upper quadrant pain, vomiting, hematemesis, and melena. Clinical examination revealed right upper quadrant tenderness and positive Murphy’s sign. Imaging studies, including ultrasound and computed tomography, confirmed a distended gallbladder with intraluminal hyperdense content and surrounding inflammation. An urgent open cholecystectomy was performed, revealing clotted blood within the gallbladder. The patient recovered uneventfully and was discharged in stable condition. Clinical discussion: HC is an uncommon but critical condition that requires prompt recognition and intervention. In this case, the coexistence of autoimmune diseases and anticoagulant therapy likely predisposed the patient to HC. Imaging played an essential role in diagnosis, and open cholecystectomy provided definitive management. Conclusion: HC should be considered in patients with SLE, APS, or coagulopathies presenting with acute abdominal symptoms. Early recognition and multidisciplinary management are essential to prevent life-threatening outcomes.

Bullous pemphigoid associated with acquired hemophilia A: A case report

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disorder caused by circulating autoantibodies against factor VIII (FVIII). In approximately 50% of the patients, the condition is associated with autoimmune diseases, cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid (BP) is a chronic autoimmune subepidermal blistering disease associated with tissue-bound and circulating autoantibodies against BP antigens 180 (BP180) and 230 (BP230). AHA-associated BP has a high mortality rate; hence, the understanding of this disease must improve. CASE SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crusts accompanied by severe pruritus for more than 20 days, and ecchymosis and swelling on his left upper arm for 3 days. Pathological examination revealed a subepidermal blister that contained eosinophils. Laboratory tests showed that the BP180 autoantibody levels had increased, isolated activated partial thromboplastin time was notably prolonged (115.6 s), and coagulation FVIII activity was extremely low (< 1.0%). Furthermore, the FVIII inhibitor titer had greatly increased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospital for effective treatment; however, he died after 2 days. CONCLUSION AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effective treatment are necessary.

Perturbations in gut microbiota composition in patients with autoimmune neurological diseases: a systematic review and meta-analysis

Studies suggest that gut dysbiosis occurs in autoimmune neurological diseases, but a comprehensive synthesis of the evidence is lacking. Our aim was to systematically review and meta-analyze the correlation between the gut microbiota and autoimmune neurological disorders to inform clinical diagnosis and therapeutic intervention. We searched the databases of PubMed, Embase, Web of Science, and the Cochrane Library until 1 March 2024 for research on the correlation between gut microbiota and autoimmune neurological disorders. A total of 62 studies provided data and were included in the analysis (n = 3,126 patients, n = 2,843 healthy individuals). Among the included studies, 42 studies provided data on α-diversity. Regarding α-diversity, except for Chao1, which showed a consistent small decrease (SMD = −0.26, 95% CI = −0.45 to −0.07, p < 0.01), other indices demonstrated no significant changes. While most studies reported significant differences in β-diversity, consistent differences were only observed in neuromyelitis optica spectrum disorders. A decrease in short-chain fatty acid (SCFA)-producing bacteria, including Faecalibacterium and Roseburia, was observed in individuals with autoimmune encephalitis, neuromyelitis optica spectrum disorders, myasthenia gravis, and multiple sclerosis. Conversely, an increase in pathogenic or opportunistic pathogens, including Streptococcus and Escherichia-Shigella, was observed in these patients. Subgroup analyses assessed the confounding effects of geography and immunotherapy use. These findings suggest that disturbances of the gut flora are associated with autoimmune neurological diseases, primarily manifesting as non-specific and shared microbial alterations, including a reduction in SCFA-producing bacteria and an increase in pathogenic or opportunistic pathogens.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023410215.

Advancing Optical Coherence Tomography Diagnostic Capabilities: Machine Learning Approaches to Detect Autoimmune Inflammatory Diseases.

In many parts of the world including India, the prevalence of autoimmune inflammatory diseases such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis (MS) is rising. A diagnosis is often delayed due to insufficient diagnostic tools. Machine learning (ML) models have accurately differentiated eyes of patients with MS from those of healthy controls (HCs) using optical coherence tomography (OCT)-based retinal images. Examining OCT characteristics may allow for early differentiation of these conditions. The objective of this study was to determine feasibility of ML analyses to distinguish between patients with different autoimmune inflammatory diseases, other ocular diseases, and HCs based on OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layers (INLs). Eyes of people with MS (n = 99 patients), NMOSD (n = 40), MOGAD (n = 74), other ocular diseases (OTHER, n = 16), and HCs (n = 54) from the Mangalore Demyelinating Disease Registry were included. Support vector machine (SVM) classification models incorporating age, pRNFL, GCIPL, and INL were performed. Data were split into training (70%) and testing (30%) data and accounted for within-patient correlations. Cross-validation was used in training to choose the best parameters for the SVM model. Accuracy and area under receiver operating characteristic curves (AUROCs) were used to assess model performance. The SVM models distinguished between eyes of patients with each condition (i.e., MOGAD vs NMOSD, NMOSD vs HC, MS vs OTHER, etc) with strong discriminatory power demonstrated from the AUROCs for these comparisons ranging from 0.81 to 1.00. These models also performed with moderate to high accuracy, ranging from 0.66 to 0.81, with the exception of the MS vs NMOSD comparison, which had an accuracy of 0.53. ML models are useful for distinguishing between autoimmune inflammatory diseases and for distinguishing these from HCs and other ocular diseases based on OCT measures. This study lays the groundwork for future deep learning studies that use analyses of raw OCT images for identifying eyes of patients with such disorders and other etiologies of optic neuropathy.

Early Autologous Fat Grafting for Facial Lipoatrophy Caused by Undifferentiated Connective Tissue Disease

A variety of autoimmune disorders that do not fit the criteria for specific connective tissue diseases are included in the category of undifferentiated connective tissue disease (UCTD). Facial lipoatrophy is an underreported presenting characteristic, despite the prevalence of cutaneous symptoms. The aim of this article is to demistrate the potential of early autologous fat grafting (AFG) in treating facial depressions caused by UCTD. A 29-year-old woman with UCTD presented with progressive bilateral cheek depressions and was managed with tacrolimus lately. Sheet-like depressions can be found during physical examination, which are more pronounced on the left cheek. The patient underwent AFG surgery to the affected areas. During the surgery, a total of 30 mL of fat was harvested from the lower abdomen, and 5.0 mL of pure fat was eventually gained and grafted to the bilateral cheek depressions. Satisfying aesthetic outcomes were achieved with smooth facial contours. Through the use of adipose-derived stem cells, early AFG in the active stage of UCTD can enhance face appearance while also possibly having local anti-inflammatory and antifibrotic benefits. It also has important implications for improving the look and slowing the progression of other autoimmune diseases that affect the face.

CX3CR1+ age-associated CD4+ T cells contribute to synovial inflammation in late-onset rheumatoid arthritis

BackgroundRecent evidence suggests that clonally expanded cytotoxic T cells play a role in various autoimmune diseases. Late-onset rheumatoid arthritis (LORA) exhibits unique characteristics compared to other RA forms, suggesting distinct immunological mechanisms. This study aimed to examine the involvement of cytotoxic T cells in LORA.MethodsFresh peripheral blood samples were collected from 78 treatment-naïve active RA patients, 12 with difficult-to-treat RA, and 16 healthy controls. Flow cytometry was employed to measure the proportions of CX3CR1+cytotoxic CD4+ and CD8+ T cells in these samples. Additionally, immunohistochemical staining was performed on lymphoid node and synovial biopsy samples from patients with RA.ResultsCX3CR1+cytotoxic CD4+ T cells were specifically increased in untreated, active patients with LORA, displaying features of CXCR3mid age-associated T helper cells known as “ThA”. CX3CR1⁺CD4⁺ T cells were identified as a cytotoxic ThA subset, as nearly all of these cells specifically expressed granzyme B. These cells were observed in enlarged lymph nodes and were found to infiltrate synovial tissues from patients with LORA. The proportions of CX3CR1+CD4+ T cells positively correlated with arthritis activity in LORA. The number of cells decreased after treatment with methotrexate, tumor necrosis factor inhibitors, and interleukin-6 inhibitors, whereas T-cell activation modulators did not affect them. Moreover, PD-1+CD38+CX3CR1+CD4+ T cells were identified as a treatment-resistant T cell subset that was characteristically increased in difficult-to-treat RA. CX3CR1+CD8+ T cells showed no significant difference between RA patients and healthy individuals, and no correlation with disease activity was observed. However, a correlation with age was observed in RA patients.ConclusionsOur findings suggest that the immunopathogenesis of RA differs by age of onset, with CX3CR1+ age-associated cytotoxic CD4+ T cells playing a significant role in LORA. Additionally, the presence of a specific CX3CR1+ T cell subset may be linked to treatment resistance.

Metabolically Aberrant Extracellular Mitochondria Induce Oxidative Endotheliopathy in Traumatic Brain Injury

Traumatic brain injury (TBI) causes endothelial injuries both at the site of injury and in remote regions of the brain. TBI-induced endotheliopathy also disseminates to extracranial organs, such as the lungs. This TBI-induced systemic endotheliopathy has been extensively reported in clinical studies, but its underlying mechanism remains poorly understood. Here we report results from a study designed to investigate the role of extracellular mitochondria (exMt) in TBI-induced endotheliopathy. We showed that exMt are released from injured brains into the circulation, reaching a maximal level of 1.8x104/µl at 3 hours after mice were subjected to severe TBI. These exMt express peroxidized cardiolipin on their surface and generate significant amounts of reactive oxygen species, but they produce less ATP compared to intracellular mitochondria of normal cells. When infused into non-injured mice, exMt induce systemic endotheliopathy defined by increased endothelial permeability, tissue edema, and perivascular bleeding. We further demonstrated that endothelial cells endocytose exMt through the lipid-scavenging receptor CD36 and dynamin-driven clathrin-mediated pathway. The endocytosed exMt interacted with the endoplasmic reticulum (ER) of ECs through newly formed mitochondria-associated membrane, leading to intracellular ER stress and resultant apoptosis. This study delineates a new pathway of exMt-induced endotheliopathy during acute TBI. It also demonstrates a causal role of exMt in endothelial injuries associated with (poly)trauma, severe infection, and autoimmune diseases.

The absolute number of circulating Treg cells is reduced in difficult-to-treat RA patients and is ameliorated by low-dose IL-2

ObjectiveCirculating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of immune homeostasis. Perhaps, there is a unique immune cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of autoimmune diseases. This study focused on the uniqueness of D2T RA lymphocyte subsets and the feasibility of low-dose IL-2 therapy.MethodsParticipants included 1,042 RA patients who were divided into three groups according to the presence or absence of treatment and their response to treatment in the last 6 months—new group, treated group, and D2T group—and 339 healthy controls (HCs). A total of 381 patients—107, 151, and 123 in each of the three experimental groups—received low-dose IL-2 treatment [0.5 million international units (MIU) per day, subcutaneous injection from day 1 to day 5]. The absolute numbers of peripheral blood lymphocyte subsets were detected by flow cytometry (FCM) and serum cytokine levels were detected by flow cytometry bead array (CBA).ResultsThe absolute number of T, CD4+ T, and Treg cells in the D2T RA group was lower than that in the HC, new, and treated RA groups. Compared with the HC and new RA group, the ratio of Th17/Treg cells in the D2T RA group increased. The new, treated, and D2T RA groups had higher cytokine levels than the HC. The number of Treg cells in RA patients was negatively correlated with the disease activity index. Treg cells in the new, treated, and D2T RA groups could be increased by low-dose IL-2 therapy without any side effects.ConclusionsThe number of lymphocytes and subsets in D2T RA patients was reduced, especially Treg cells, resulting in a shift in the balance of effector T cells/Treg cells toward effector T cells, which is ameliorated by low-dose IL-2 without obvious side effects.

The Value of MRI and Radiomics for the Diagnostic Evaluation of Thyroid-Associated Ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is a vision-threatening autoimmune disease that involves the extraocular muscles (EOMs) and periorbital fat. Typical signs of TAO include eyelid recession, proptosis, diplopia, and decreased visual acuity. As a self-limited disease, there is major bipolarity in clinical outcomes in TAO population. The early diagnosis and prediction of these refractory and relapsed patients is essential. Unfortunately, commonly used tools such as CAS/NOSPECTS, are based on clinical symptoms and signs alone, have significant limitations. Some imaging techniques or examinations, such as magnetic resonance imaging (MRI), can be very effective in assisting TAO assessment, from exhaustive whiteboard notes to optimized patient outcomes. Being one of the most commonly used and accurate objective examinations for TAO assessment, MRI boosts no ionizing radiation, high soft tissue contrast, better reflection of tissue water content, and the ability to quantify multiple parameters. In addition, novel MR sequences are becoming increasingly more familiar in TAO and other areas of clinical and scientific research. Moreover, radiomics, a method involving the extraction of a large number of features from medical images through algorithms, is a more recent approach used in the analysis and characterization of TAO data. Thus, this review aims to summarize and compare the value of routine and novel functional MRI sequences and radiomics prediction models in the diagnosis and evaluation of TAO.

Occupational dust and chemical exposures and the development of autoimmune rheumatic diseases.

Although the association between certain occupational exposures and the development of autoimmune rheumatic disease was first described over a century ago, this association has only become more widely recognized in the past 10 years because of the use of high-silica-content engineered stone in construction and home renovation. There is now a substantial and growing body of evidence that occupational dust and chemical exposure, be it through mining, stonemasonry, building or other trades, increases the risk of various systemic autoimmune rheumatic diseases (SARDs) including rheumatoid arthritis and systemic sclerosis. Although the pathogenic mechanisms of silica-induced autoimmunity are not fully elucidated, it is thought that alveolar macrophage ingestion of silica and the ensuing phagosomal damage is an initiating event that ultimately leads to production of autoantibodies and immune-mediated tissue injury. The purportedly causal association between occupational exposure to chemicals, such as organic solvents, and an increased risk of SARDs is less frequently recognized compared with silica dust, and its immunopathogenesis is less well understood. An appreciation of the importance of occupational dust and chemical exposures in the development of SARDs has implications for workplace health and safety regulations and offers a unique opportunity to better understand autoimmune disease pathogenesis and implement preventative strategies.

Translocating gut pathobiont Enterococcus gallinarum induces T H 17 and IgG3 anti-RNA–directed autoimmunity in mouse and human

Chronic autoimmune diseases often lead to long-term sequelae and require lifelong immunosuppression because of an incomplete understanding of the triggers and drivers in genetically predisposed patients. Gut bacteria that escape the gut barrier, known as translocating gut pathobionts, have been implicated as instigators and perpetuators of extraintestinal autoimmune diseases in mice. The gut microbial contributions to autoimmunity in humans remain largely unclear, including whether specific pathological human adaptive immune responses are triggered by such pathobionts. Here, we show that the translocating pathobiont Enterococcus gallinarum can induce both human and mouse interferon-γ + T helper 17 (T H 17) differentiation and immunoglobulin G3 (IgG3) subclass switch of anti– E. gallinarum RNA antibodies, which correlated with anti-human RNA autoantibody responses in patients with systemic lupus erythematosus (SLE) and autoimmune hepatitis, two extraintestinal autoimmune diseases. E. gallinarum RNA, but not human RNA, triggered Toll-like receptor 8 (TLR8), and TLR8-mediated human monocyte activation promoted human T H 17 induction by E. gallinarum . Translocation of the pathobiont triggered increased anti-RNA autoantibody titers that correlated with renal autoimmune pathophysiology in murine gnotobiotic lupus models and with disease activity in patients with SLE. These studies elucidate cellular mechanisms of how a translocating gut pathobiont induces systemic human T cell– and B cell–dependent autoimmune responses and provide a framework for developing host- and microbiota-derived biomarkers and targeted therapies in autoimmune diseases.

Efficacy of CLT4A variants as immunoregulatory molecules among Vitiligo patients in Saudi Arabia

Vitiligo is a skin depigmentation condition caused by the immune-mediated perdition of melanocytes. In vitiligo, cytotoxic T-lymphocytes damage melanocytes, causing skin depigmentation. The Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene has been reported to be related to vitiligo and other autoimmune diseases. The purpose of this study was to explore the molecular involvement of rs231775 and rs3087243 SNPs in the CTLA4 gene in vitiligo patients. The recruitment was based on the sample size calculation and based on it, we have recruited 300 Saudi individuals who were evenly divided into vitiligo cases and controls. Extracted genomic DNA was utilized to amplify rs231775 and rs3087243 SNPs in the CTLA4 gene, which were subsequently digested and verified using Sanger sequencing. The polymerase chain reaction and restriction fragment length polymorphism analysis laboratory data were stored in Excel and used for further statistical analysis. Although baseline details had no correlation (p > 0.05) between the two groups, Hardy-Weinberg Equilibrium analysis was in agreement with the vitiligo patients (p > 0.05). The genotype and allele frequencies were frequently associated (p < 0.05) with rs3087243, and rs231775 SNP showed a nominal association with GG genotype and G allele (p < 0.05). The specific relationship in vitiligo cases was revealed by MDR, GDMR, and linkage disequilibrium (p < 0.05), but not with haplotype analysis (p > 0.05). Thus, the study concluded that rs3087243 SNP was associated and rs231775 SNP showed a nominal association with vitiligo in the Saudi population.

Effect of Feeding Human Milk on Development of the Infant Immune System and Allergic Outcomes-An Area of Research Challenge and Need.

Surprisingly little is known about the effect of breastfeeding on the infant's immune system development. Systematic reviews have suggested the role of breastfeeding in the prevention against asthma, autoimmune diseases, inflammatory bowel disease, and childhood leukemia. However, studies on atopic disease suffer from reverse causation, small size, and those assessing food allergy (FA) have often relied on parent-reported outcomes. Randomized controlled trials (RCTs) are not possible for ethical reasons. In addition, epidemiological studies have not considered that there is a large interindividual variation in human milk (HM) composition and feeding at the breast versus pumped HM potentially impacting the effect of breastfeeding between mothers. While prevention strategies such as early introduction of highly allergenic food are impactful in preventing peanut and egg allergies, implementation of early introduction guidelines has been slow, and many infants are already sensitized by 4-6 months of age. To be more effective, primary prevention strategies must commence much earlier, during breastfeeding. There are studies that imply a definitive effect of breastfeeding on the gut microbiome and regulatory T cells (Tregs) as well as a higher rate of FA in populations with historically low rates of breastfeeding. These provide a strong rationale for assessing the effect of feeding HM in the context of HM composition and mode of feeding on immune development. The lack of well-conducted, large studies assessing the role of breastfeeding and HM composition in the development of immune system development is a significant gap when designing prevention strategies.

Encephalopathy in Sjogren’s Syndrome - A Distinct Neurological Presentation

Sjogren’s syndrome (SS) is an autoimmune disorder characterized by lymphocytic and plasma infiltration of exocrine glands, resulting in dry mouth and kerato-conjunctivitis sicca. The clinical symptoms may range from mucosal dryness to more systematic complaints. Sjogren's syndrome (SS) may be complicated by neurological manifestations.1 We report a 36-year-old woman presenting with quadriparesis, started as lower limb weakness which progressed to the upper limbs, having Guillain-Barre syndrome like pattern. MRI brain showed altered signal intensity in the brainstem, predominantly centered in the pons labelled as autoimmune brainstem encephalitis with distal RTA. With differentials as clippers, autoimmune disease and de-mylinating disease patient underwent an Autoimmune panel which showed Antinuclear Antibody showing speckled SSA/RO pattern and antibodies to SSB/LA were positive suggestive of Sjogren’s syndrome. The diagnosis was confirmed with a minor salivary gland biopsy from the lower lip which was definitive of Sjogren’s syndrome. Patient showed excellent improvement on pulsed steroid therapy. Therefore, this case illustrates a rare, heralding manifestation of Sjogren’s syndrome as brainstem encephalitis with definitely diagnosis based on minor salivary gland biopsy showing complete recovery on early detection and management.

Quantification of mycophenolic acid in plasma by isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method.

Accurate measurements of plasma mycophenolic acid (MPA) are essential for therapeutic drug monitoring in transplant recipients and autoimmune diseases. The performance of plasma mycophenolic acid routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of plasma mycophenolic acid measurements. In this study, sample preparation was based on protein precipitation with methanol followed by further dilution. The mycophenolic acid was quantified by the isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with electrospray ionization in positive ion mode. According to the Clinical and Laboratory Standards Institute (CLSI) documents C62-A and C50-A, the basic analytical performance of the candidate reference method was verified, such as linearity, limit of quantification, matrix effect, precision, accuracy, and uncertainty. Moreover, the candidate reference measurement procedure was compared with the routine liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a clinical laboratory. Based on the data, the mycophenolic acid in human plasma was well detected by ID-LC-MS/MS. No apparent interferences were found with the mycophenolic acid measurement. The calibration curve for the mycophenolic acid was linear in the concentration range of 0.1-50μg/mL with a correlation coefficient of 0.9999 under the optimum experimental conditions. This method was sensitive because the low limit of quantitation (LOQ) was 0.05μg/mL. The recoveries of MPA were 98.11-98.95%. The intra-day and inter-day coefficients of variations (CV) of our method were ≤ 1.53% and ≤ 0.51%, respectively. No obvious matrix effect was observed. There was a good correlation between this method and the clinical routine LC-MS/MS method. To sum up, we established and validated a reliable plasma MPA method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for plasma MPA routine measurements.

Systematic review of bidirectional interaction between gut microbiome, miRNAs, and human pathologies

MicroRNAs (miRNAs) and the gut microbiome are key regulators of human health, with emerging evidence highlighting their complex, bidirectional interactions in chronic diseases. miRNAs, influence gene expression and can modulate the composition and function of the gut microbiome, impacting metabolic and immune processes. Conversely, the microbiome can affect host miRNA expression, influencing inflammatory pathways and disease susceptibility. This systematic review examines recent studies (2020–2024) focusing exclusively on human subjects, selected through rigorous inclusion and exclusion criteria. Studies were included if they investigated the interaction between miRNAs and the gut microbiome in the context of gastrointestinal diseases, obesity, autoimmune diseases, cognitive and neurodegenerative disorders, and autism. In vitro, in vivo and in silico analyses were excluded to ensure a strong translational focus on human pathophysiology. Notably, miRNAs, stable and abundant in patients, are emerging as promising biomarkers of microbiome-driven inflammation. This systematic review provides an overview of miRNAs, their regulatory effects on bacterial strains, and their associations with specific diseases. It also explores therapeutic advances and the potential of miRNA-based therapies to restore microbial balance and reduce inflammation.

Diffuse Parenchymal Lung Diseases due to Overlap syndrome (Rheumatoid arthritis and Systemic Sclerosis) with Sjogren syndrome and Psoriasis: A Rare case report

The diffuse parenchymal lung diseases (DPLDs) are a heterogeneous group of conditions affecting the pulmonary parenchyma (interstitial) and/or alveolar lumen. Since DPLD in overlap syndromes has a poor prognosis, extensive work up should be performed even when clinical evidence of only one autoimmune disease is present. DPLD is a frequent manifestation of connective tissue diseases (CTDs), with incidence and prevalence variously assessed in the literature but reported in up to 30% of patients, with higher frequency in rheumatoid arthritis (RA) and systemic sclerosis (SSc). However, Sjogren’s syndrome (SS) is a chronic inflammatory disease characterized by lymphocytic infiltrates in the exocrine glands, mainly the salivary and lacrimal glands. DPLD is found in 3-11% of the patients with primary Sjogren’s syndrome, often leading to life-threatening complications. When combined, the diagnosis is often missed or delayed, which can lead to an increased incidence of long-term morbidity and mortality. We present an interesting case of DPLD due to RA-SSc overlap syndrome and Sjogren syndrome – a 53-year-old non-diabetic, normotensive, non-smoker, cotton-wool cloth weaver, married, Muslim female presented with progressively increasing dry, distressing non-productive cough for 3 years which was persistent throughout the day without any seasonal or diurnal variation. She complaints of insidious onset, gradually progressive breathlessness, with mMRC grade-3 at present from initial mMRC grade-0. There was no history of orthopnoea, palpitation, chest pain or any swelling of body. She also complaints of symmetrical inflammatory polyarthritis for 6 months involving small joints of hands, wrist, elbow, feet; not associated with joint swelling, oral ulcer, photosensitivity. She developed painless, non-itchy salt and pepper skin pigmentation along with partly scaly over forehead, back of chest, around neck, upper and lower limbs but no muscle aches and proximal myopathy. We emphasized on inter-professional consultation in the diagnosis and treatment of such a rare case. Mugda Med Coll J. 2024; 7(2): 139-143

Controversies Surrounding IGF-I Receptor Involvement in Thyroid-Associated Ophthalmopathy.

Background: Thyroid-associated ophthalmopathy (TAO, aka thyroid eye disease [TED], Graves' orbitopathy) remains poorly understood and inadequately treated since its initial description. It is disfiguring, can threaten vision, and represents an autoimmune process closely associated with thyroid disease. Unambiguous connections linking TAO to the glandular maladies of Graves' disease (GD) remain incompletely clarified. Detecting the thyrotropin receptor (TSHR) in periocular tissues suggests that this cell-surface protein represents a shared autoantigen with the thyroid gland, but we now know that its expression is ubiquitous. Most patients with TAO have relatively high circulating levels of activating anti-TSHR autoantibodies. Emerging more recently is the importance of insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of TAO. The TSHR/IGF-IR signaling complex apparently drives circulating fibrocytes and the unique phenotypes of fibroblasts inhabiting the TAO orbit (GD-OF). Methods: The PubMed database was scanned for articles dating back to the earliest time periods covered. Keywords used for primary searches included thyroid-associated ophthalmopathy, Graves' orbitopathy, TED, orbit, TSH receptor, IGF-I receptor, and autoimmune thyroid disease. Secondary searches used numerous other search terms. Results: GD-OF have been characterized extensively as being particularly responsive to the immunological factors and key effectors in TAO pathogenesis. Both TSHR and IGF-IR are overexpressed by GD-OF and CD34+ fibrocytes and form a signaling complex. They are activated through this TSHR/IGF-IR complex to produce large amounts of hyaluronan and express multiple cytokines. This complex mediates cellular responses to pathogenic IgGs in TAO. CD34+ fibrocytes and CD34+ OF also express relatively high levels of multiple thyroid autoantigens. Identifying IGF-IR as a key component of a receptor complex and its intertwining signaling activities with those of TSHR has led to a targeted medical therapy for TAO. This therapy involves the selective systemic inhibition of IGF-IR. Conclusions: Much has been learned over the preceding decades about the pathogenesis of TAO. Among these is the identification of IGF-IR as a pivotal component underpinning the disease. This has led directly to development of an effective targeted therapy. Important gaps in our understanding persist, and current therapies have limitations. Thus, despite these advancements, considerably more remains to be achieved.

Clinical Management in Multiple Sclerosis

This review aims to provide a comprehensive overview of the main types, subtypes, clinical manifestations, and current therapeutic strategies for multiple sclerosis, emphasizing recent advancements and clinical challenges. Multiple Sclerosis (MS) is a demyelinating, chronic, autoimmune, and inflammatory disease that affects the Central Nervous System (CNS). Its classification has the following subtypes: Relapsing-Remitting (RRMS), Secondary-Progressive (SPMS), and Primary-Progressive (PPMS), including rarer subtypes such as Clinically Isolated Syndrome (CIS), Radiologically Isolated Syndrome (RIS), Balo’s Concentric Sclerosis (BCS), Schilder’s Disease (SD), and Progressive-Relapsing MS (PRMS). This article divides the various treatments for MS into the following three categories: acute relapse management, symptomatic treatments, and Disease-Modifying Treatments (DMTs). The latter represents revolutionary research in MS, since they are the drugs considered as the best treatment alternatives for this disease.