Organ-specific Diseases Research Articles

Complete Blood Collection-based Systemic Inflammation Biomarkers as a Severity Biomarker in Alopecia Areata: A Cross-sectional Study.

Previous studies have suggested that alopecia areata (AA) is an organ-specific disease characterized by loss of immune privilege of hair follicles. However, an increasing body of research indicates that it not only affects the skin but may also be accompanied by systemic inflammatory reactions. Therefore, searching for simple and easily available biomarkers to describe the underlying systemic inflammation in AA patients is of great clinical significance. Complete blood collection-based systemic inflammation biomarkers have been shown to be associated with the severity and prognosis of various skin and autoimmune diseases. They involve multiple cell lineages and can reveal different pathways of immune-inflammatory responses. The aim of this study was to investigate the level of complete blood collection-based systemic inflammation biomarkers in patients with AA, and to analyse their relationship with the disease severity. A total of 302 AA patients and 296 healthy controls were included in this study and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), and white blood cell/lymphocyte ratio (WLR) were calculated. The differences in these indicators between the 2 groups were compared, and the relationship between NLR, PLR, SII, WLR, and the risk of severe AA were analysed. AA patients had higher NLR, SII, and WLR compared with healthy controls (p = 0.004, 0.002, and 0.002 respectively). PLR and SII were higher in the severe AA group compared with the mild-to-moderate AA patients (p = 0.005 and 0.011 respectively). The risk of severe AA increased with the increasing of PLR, SII, NLR, and WLR (p for trend was 0.001, 0.006, 0.022, and 0.021, respectively). The levels of systemic inflammation biomark-ers in AA patients are higher than in healthy people. NLR, PLR, SII, and WLR are risk factors for severe AA, suggesting a close association between systemic inflammation and disease occurrence in AA patients.

QSOX2 Deficiency-induced short stature, gastrointestinal dysmotility and immune dysfunction.

Postnatal growth failure is often attributed to dysregulated somatotropin action, however marked genetic and phenotypic heterogeneity exist. We report five patients from three families who present with short stature, immune dysfunction, atopic eczema and gastrointestinal pathology associated with recessive variants in QSOX2. QSOX2 encodes a nuclear membrane protein linked to disulphide isomerase and oxidoreductase activity. Loss of QSOX2 disrupts Growth hormone-mediated STAT5B nuclear translocation despite enhanced Growth hormone-induced STAT5B phosphorylation. Moreover, patient-derived dermal fibroblasts demonstrate Growth hormone-induced mitochondriopathy and reduced mitochondrial membrane potential. Located at the nuclear membrane, QSOX2 acts as a gatekeeper for regulating stabilisation and import of phosphorylated-STAT5B. Altogether, QSOX2 deficiency modulates human growth by impairing Growth hormone-STAT5B downstream activities and mitochondrial dynamics, which contribute to multi-system dysfunction. Furthermore, our work suggests that therapeutic recombinant insulin-like growth factor-1 may circumvent the Growth hormone-STAT5B dysregulation induced by pathological QSOX2 variants and potentially alleviate organ specific disease.

The metabolic profiles of endogenous and exogenous substances in a poor metabolizer of humanized CYP2D6 model

Background: Species differences in CYP2D6 drug metabolism complicate the extrapolation of in vivo pharmacokinetic data to humans and impact the prediction of drug responses. This study aimed to develop an in vivo model to predict human responses to CYP2D6 metabolized compounds and to evaluate medication risks and disease development.Methods: We used embryonic stem cell (ES) targeting and CRISPR-Cas9 technology to create a humanized CYP2D6 mouse model by inserting the human wild-type CYP2D6 gene and knocking out the mouse Cyp2d locus. Metoprolol was used as the substrate probe to examine the pharmacokinetic properties of exogenous substances, tissue distribution, and in situ metabolism of CYP2D6. Untargeted and quantitative metabolomics analyses compared endogenous substance metabolism between different species of CYP2D6 enzymes.Results: No significant differences in CYP2D6 homologous protein distribution and expression of primary metabolic organs were found between humanized CYP2D6 mice and wild-type (WT) mice. The activity and metabolic capacity of CYP2D6 in humanized mice were substantially lower than homologous Cyp2d22 of WT mice in metabolizing metoprolol. The levels of several glycerolipids and glycerophospholipid-related metabolites were down-regulated in humanized CYP2D6 mice. Triglyceride TG (14:0_22:6_22:6) was significantly downregulated in male and female humanized mice, suggesting a strong association with reduced CYP2D6 activity.Conclusions: This study established a robust animal model to investigate human CYP2D6-mediated metabolic profiles of exogenous and endogenous compounds, predict medication risks, and explore the potential roles of CYP2D6 in organ-specific toxicity and disease development.

Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

Anifrolumab in Refractory Systemic Lupus Erythematosus: A Real-World, Multicenter Study.

To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE). The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score (P = 0.01), and physician global assessment (P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P < 0.001) and in tender (P = 0.03) and swollen (P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders. This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

Plasma proteomics in the UK Biobank reveals youthful brains and immune systems promote healthspan and longevity.

Organ-derived plasma protein signatures derived from aptamer protein arrays track organ-specific aging, disease, and mortality in humans, but the robustness and clinical utility of these models and their biological underpinnings remain unknown. Here, we estimate biological age of 11 organs from 44,526 individuals in the UK Biobank using an antibody-based proteomics platform to model disease and mortality risk. Organ age estimates are associated with future onset of heart failure (heart age HR=1.83), chronic obstructive pulmonary disease (lung age HR=1.39), type II diabetes (kidney age HR=1.58), and Alzheimer's disease (brain age HR=1.81) and sensitive to lifestyle factors such as smoking and exercise, hormone replacement therapy, or supplements. Remarkably, the accrual of aged organs progressively increases mortality risk while a youthful brain and immune system are uniquely associated with disease-free longevity. These findings support the use of plasma proteins for monitoring organ health and the efficacy of drugs targeting organ aging disease.

In vitro immunity: an overview of immunocompetent organ-on-chip models.

Impressive advances have been made to replicate human physiology in vitro over the last few years due to the growth of the organ-on-chip (OoC) field in both industrial and academic settings. OoCs are a type of microphysiological system (MPS) that imitates functional and dynamic aspects of native human organ biology on a microfluidic device. Organoids and organotypic models, ranging in their complexity from simple single-cell to complex multi-cell type constructs, are being incorporated into OoC microfluidic devices to better mimic human physiology. OoC technology has now progressed to the stage at which it has received official recognition by the Food and Drug Administration (FDA) for use as an alternative to standard procedures in drug development, such as animal studies and traditional in vitro assays. However, an area that is still lagging behind is the incorporation of the immune system, which is a critical element required to investigate human health and disease. In this review, we summarise the progress made to integrate human immunology into various OoC systems, specifically focusing on models related to organ barriers and lymphoid organs. These models utilise microfluidic devices that are either commercially available or custom-made. This review explores the difference between the use of innate and adaptive immune cells and their role for modelling organ-specific diseases in OoCs. Immunocompetent multi-OoC models are also highlighted and the extent to which they recapitulate systemic physiology is discussed. Together, the aim of this review is to describe the current state of immune-OoCs, the limitations and the future perspectives needed to improve the field.

Nodular/Keloidal Scleroderma with No Systemic Involvement-A Case Report and a Review of the Literature.

Nodular or keloidal scleroderma is a rare condition with unclear cause and sporadic mentions in the medical literature. It was first recognized in the 19th century, yet its classification is still debated due to the limited number of reported cases. This rare variant of scleroderma is associated with either progressive systemic sclerosis or localized morphea. Clinically, it presents with asymptomatic nodules or plaques, resembling spontaneous keloid formation, often found on the trunk and proximal extremities. Recent literature reviews show a predominance of women with a mean age of 44 years. Diagnosis relies on clinical and histopathological findings, which usually show overlapping features of both scleroderma and true keloids, secondarily to an excessive fibrosing reaction attributed to collagen formation. We present an unusual case of a 70-year-old female patient who displayed the coexistence of two distinct subtypes of morphea (nodular/keloidal and linear), and exclusive skin involvement, which contrasts with the typical presentation of nodular/keloidal scleroderma, often associated with organ-specific disease. However, recent publications have diverged from previous ones regarding systemic sclerosis, with no systemic involvement reported between 2018 and 2024, which we evaluated in our descriptive literature review. With less than 50 cases reported in total, our case underlines the importance of recognizing this rare disease, ensuring appropriate evaluation, treatment, and follow-up.

A mouse model of autoimmune inner ear disease without endolymphatic hydrops

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels.

Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.

Fibrosis-on-Chip: A Guide to Recapitulate the Essential Features of Fibrotic Disease.

Fibrosis, which is primarily marked by excessive extracellular matrix (ECM) deposition, is a pathophysiological process associated with many disorders, which ultimately leads to organ dysfunction and poor patient outcomes. Despite the high prevalence of fibrosis, currently there exist few therapeutic options, and importantly, there is a paucity of in vitro models to accurately study fibrosis. This review discusses the multifaceted nature of fibrosis from the viewpoint of developing organ-on-chip (OoC) disease models, focusing on five key features: the ECM component, inflammation, mechanical cues, hypoxia, and vascularization. The potential of OoC technology is explored for better modeling these features in the context of studying fibrotic diseases and the interplay between various key features is emphasized. This paper reviews how organ-specific fibrotic diseases are modeled in OoC platforms, which elements are included in these existing models, and the avenues for novel research directions are highlighted. Finally, this review concludes with a perspective on how to address the current gap with respect to the inclusion of multiple features to yield more sophisticated and relevant models of fibrotic diseases in an OoC format.

Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis.

Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis. Since platelets have been reported to modulate immune responses, we aimed to determine the role of platelets in TMEV infection. In transcriptome analyses of platelets, distinct sets of immune-related genes, including major histocompatibility complex (MHC) class I, were up- or downregulated in TMEV-infected mice at different time points. We depleted platelets from TMEV-infected mice by injecting them with platelet-specific antibodies. The platelet-depleted mice had significantly fewer viral antigen-positive cells in the CNS. Platelet depletion reduced the severities of TMEV-IDD and myocarditis, although the pathology scores did not reach statistical significance. Immunologically, the platelet-depleted mice had an increase in interferon (IFN)-γ production with a higher anti-TMEV IgG2a/IgG1 ratio. Thus, platelets may play roles in TMEV infection, such as gene expression, viral clearance, and anti-viral antibody isotype responses.

The application strategy of liposomes in organ targeting therapy.

Liposomes-microscopic phospholipid bubbles with bilayered membrane structure-have been a focal point in drug delivery research for the past 30 years. Current liposomes possess a blend of biocompatibility, drug loading efficiency, prolonged circulation and targeted delivery. Tailored liposomes, varying in size, charge, lipid composition, and ratio, have been developed to address diseases in specific organs, thereby enhancing drug circulation, accumulation at lesion sites, intracellular delivery, and treatment efficacy for various organ-specific diseases. For further successful development of this field, this review summarized liposomal strategies for targeting different organs in series of major human diseases, including widely studied cardiovascular diseases, liver and spleen immune diseases, chronic or acute kidney injury, neurodegenerative diseases, and organ-specific tumors. It highlights recent advances of liposome-mediated therapeutic agent delivery for disease intervention and organ rehabilitation, offering practical guidelines for designing organ-targeted liposomes. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures.

Organ aging signatures in the plasma proteome track health and disease

Animal studies show aging varies between individuals as well as between organs within an individual1–4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20–50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer’s disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.

Subacute thyroiditis following COVID-19 vaccination: Case presentation.

Background: Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19.Purpose: The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine.Research design and study sample: Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal.Data collection and/or Analysis: Data collected during the disease are integral to the medical record.Results: Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.

Clinical characteristics and outcomes of patients with chronic systemic inflammatory disease in acute myocardial infarction.

Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs. This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge. Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03). A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.

Association between exposure to external airborne agents and autoimmune disease

The etiology of autoimmune disease pathogeneses remains obscure, and the impact of general environmental or occupational exposure to external airborne agents (EAA) on autoimmune diseases remains understudied. This study was conducted to elucidate the association between exposure to EAA and the risk of autoimmune diseases according to exposure type. From the NHIS-NSC (2002–2019), 17,984,963 person-years were included in the data analysis. Autoimmune diseases were categorized based on the InterLymph classification. We estimated the incidence and rate ratio of autoimmune diseases according to the EAA exposure. Association between exposure and autoimmune diseases was investigated using logistic regression analysis, adjusted for potential confounders. Of the 1,082,879 participants, 86,376 (8.0%) were diagnosed with autoimmune diseases. Among these, 208 (14.1%) experienced severe exposure to EAA. Total EAA exposure was significantly associated with any autoimmune disease (OR: 1.29, 95% CI: 1.11–1.49) and organ-specific diseases (OR: 1.28, 95% CI: 1.08–1.53). Inorganic dust exposure was associated with organ-specific diseases (OR, 1.38; 95% CI: 1.01–1.81). Exposure to other dust was significantly associated with any autoimmune disease (OR: 1.35, 95% CI: 1.10–1.66), connective tissue diseases (OR: 1.43, 95% CI: 1.03–1.99), and organ-specific diseases (OR: 1.28, 95% CI: 1.00–1.65). Exposure to EAA was predominantly related to psoriasis, rheumatoid arthritis (RA), and type 1 diabetes (T1DM). We found that exposure to EAA is a potential risk factor for autoimmune diseases, especially psoriasis, RA, and T1DM. Our findings provide insight into the role of exposure to severe airborne agents in the pathogenesis of autoimmune diseases.

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases.

Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

An Example of the Importance of Electronic Health Records from Mogadishu, Somalia: Hepatitis B Prevalence and Co-infections with Hepatitis C

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) has been discussed in detail from different aspects around the world. Current epidemiological data has critical importance in the planning and carrying out of public health policies for the prevention of transmission and spread of these infections, and the treatment of chronic infections, and to reduce the burden and mortality associated with complications such as cirrhosis and liver cancer by national health authorities and international health institutions, especially the World Health Organization. Elimination of a social health problem is possible by first raising awareness, then determining the dimensions of the problem, and planning and implementing interventions for a solution. Somalia was in the position of a region where access to diagnosis and treatment for many life-threatening diseases was difficult, aside from the monitoring of public health criteria due to the unstable situations that has continued for more than 40 years. Until recently, basic health parameters and epidemiological predictions in Somalia were monitored through estimates based on data from neighboring countries or on data obtained from small groups from Somalia immigrants settled different parts of the world. However, this situation is changing rapidly. A tertiary education and research hospital established in the capital, Mogadishu, with the coordination of the Türkiye and Somalia governments, and which has become the largest health center in the country today; contributes to understanding the extent of the serious health problems faced by the country by pioneering specialized training and scientific studies, in addition to providing health care. Electronic health records have been kept regularly since 2015 in this hospital, where hundreds of thousands of patients receive treatment or undergo health checks every year and it has been the source of numerous retrospective epidemiological studies some of which have exceeded 100 thousand cases, in different age groups and sub-populations. These studies include human immunodeficiency virus (HIV) prevalence and complications, HCV prevalence and genotype distribution, prevalence and epidemiology of parasitic infections, incidence of tuberculosis and related complications, cancer incidence and distribution, causes of blindness, thyroid diseases, antibiotic resistance profiles, and the epidemiology of various organ-specific diseases. Dozens of studies using the hospital records were included in the scientific literature between 2020 and 2023. In this study, a four-year period between November 2015 and November 2019, HBV serological test results of more than 100,000 different patients are presented. HBsAg and anti-HBs seropositivity for all age groups was found to be 8.1% (9,405/115,946) and 32.7% (25,988/79,410), respectively. When the anti-HCV test results of HBsAg positive patients were examined, the rate of HCV co-infections was found to be 0.9% (82/9,405). HBsAg and anti-HBs seropositivity were significantly higher in males than females (p&lt;0.001). HBV, HCV, and co-infection incidence tended to decrease. Conversely, vaccination rates (especially in children under one year of age) tended to increase. While the comprehensive data presented in this study provide us with important and new information about the prevalence and co-infection rates of viral hepatitis in the country, many topics including HBV genotypes, hepatitis D frequency, access to treatment rates, complication rates, and HBV vaccination rates are still waiting to be researched in Somalia. In the region where it is not possible to carry out field studies, epidemiological data provided by electronic health records have become a country's window to the world.

The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.

The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM. RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care. A previously defined 13-gene type I IFN score was modeled as a function of demographic, serologic, and clinical variables using both cross-sectional and longitudinal data. The pattern of type I IFN-driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to systemic lupus erythematosus. The median type I IFN score was higher or lower in patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5) or anti-Mi-2 antibodies, respectively, compared to patients without these antibodies. Absolute type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA-5 antibodies. Changes in the type I IFN score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation between changes in the type I IFN score and skin disease activity (Spearman's ρ=0.84-0.95). The type I IFN score is independently associated with skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti-MDA-5 status revealed that the type I IFN score is strongly correlated with skin disease activity, providing support for type I IFN blockade as a therapeutic strategy for DM.