Onset Of Autoimmune Diseases Research Articles

Dysregulation in keratinocytes drives systemic lupus erythematosus onset.

Systemic lupus erythematosus (SLE) is a complex, multiorgan autoimmune disorder. Although it is widely believed that SLE originates from immune cell dysregulation, the etiology of SLE is not yet clear. Here, we propose a new theory in which SLE can be directly initiated by molecular alterations in keratinocytes rather than immune cells. We found that the level of peroxisome proliferator-activated receptor gamma (PPARγ) is substantially reduced in the skin lesions of patients, and replicating this reduction in mice led to rapid disease onset with multiple hallmarks of SLE. As PPARγ decreases in keratinocytes, which is accompanied by increased occupancy of interferon regulatory factor 3 at the type I interferon locus, dendritic cells (DCs) are recruited to the epidermis and are activated by keratinocyte-secreted type I interferon. These activated DCs migrate to local draining lymph nodes, where they activate CD4+ T cells in a non-MHC II-dependent manner, promoting their differentiation into effector T cells and thus contributing to disease onset. Our study revealed that the dysregulation of keratinocytes can be a pathogenic driver of SLE and describes a new mouse model that mimics human SLE. Our data also emphasize the pivotal role of skin immunity in the onset of systemic autoimmune disease.

The role of the cGAS-STING pathway in chronic pulmonary inflammatory diseases.

The innate immune system plays a vital role in the inflammatory process, serving as a crucial mechanism for the body to respond to infection, cellular stress, and tissue damage. The cGAS-STING signaling pathway is pivotal in the onset and progression of various autoimmune diseases and chronic inflammation. By recognizing cytoplasmic DNA, this pathway initiates and regulates inflammation and antiviral responses within the innate immune system. Consequently, the regulation of the cGAS-STING pathway has become a prominent area of interest in the treatment of many diseases. Chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis, are characterized by persistent or recurrent lung inflammation and tissue damage, leading to diminished respiratory function. This paper explores the mechanism of action of the cGAS-STING signaling pathway in these diseases, examines the development of STING inhibitors and nanomaterial applications, and discusses the potential clinical application prospects of targeting the cGAS-STING pathway in chronic inflammatory lung diseases.

Advances in thyroid peroxidase (TPO) and thyroid stimulating hormone receptor (TSHR) biomarkers for autoimmune thyroid diseases

The development of immunological methods in the 1970s and 1980s led to the identification of thyroid peroxidase (TPO) and thyroid stimulating hormone receptor (TSHR) as key players in the onset of autoimmune thyroid diseases (AITD). TSHR is primarily associated with hyperthyroidism, while TPO is linked to hypothyroidism. Advances in understanding TPO and TSHR as biomarkers over recent decades have enhanced their clinical application. This review explores the molecular basis of TPO and TSHR as biomarkers, highlighting their importance in diagnosing AITD and their potential to guide effective therapeutic strategies. Additionally, it discusses the development of lateral flow assay (LFA) kits developed by the authors, which show promise as rapid and reliable diagnostic tools for AITD.

SARS-CoV-2 induced vitamin D deficiency and psychological stress: a manifestation of autoimmune disease onset.

The global SARS-CoV-2 pandemic significantly altered lifestyles, access to healthcare, and social interactions, introducing unprecedented physical and psychological stress all over the world. This study explores the relationship between psychological stress, vitamin D (Vit-D) levels, and autoimmune connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis. The analysis was based on over one million patient data points derived from anti-nuclear antibody (ANA) testing conducted both before and during the COVID-19 pandemic 2017-2021. In a subset of patients, longitudinal data were collected bi-yearly to yearly over 5-8 years using the same three-month criteria. The dataset was analyzed using GraphPad Prism9 using paired t-tests or ordinary one-way ANOVA with a significance threshold of p < 0.05 to ensure robust correlations between the variables. Data indicated that Vit-D levels peaked between 2017 and 2019 before declining, while ANA data demonstrated a rise in autoimmune connective tissue disease cases during the pandemic, reaching a peak in 2021. A clear correlation was observed, with autoimmune disease incidence increasing as Vit-D levels decreased. In-depth case analysis revealed that declining Vit-D levels preceded higher ANA titers and increased autoimmune disease severity, whereas improvements in Vit-D levels were associated with reduced ANA titers and less severe disease manifestations. The findings suggest that maintaining mental health and ensuring adequate Vit-D supplementation could be essential strategies for mitigating autoimmune disease risks and maintaining immune stability, particularly in pandemic scenarios. Clinically, these results underscore the need for early interventions targeting both psychological well-being and Vit-D levels to reduce the burden of autoimmune diseases.

Cervical myelopathy as an atypical presentation of antineutrophil cytoplasmic antibody-associated vasculitis in a patient affected by silicosis: a case report and literature overview.

We describe the case of a 73-year-old man affected by pneumoconiosis, secondary to silica dust exposure, who was diagnosed with antineutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA)-related cervical myelitis. Pneumoconiosis is reported to trigger autoantibody production and the onset of different autoimmune diseases, including ANCA-associated vasculitis (AAV). MPA is an AAV of the small vessels that can often affect the nervous system, although involvement of the spinal cord in the form of myelitis is described as an anecdotal occurrence. Our experience suggests that an autoimmunity workup should be considered for patients with pneumoconiosis who present with neurological symptoms consistent with AAV.

The Role of Gut Microbiome Alterations in the Pathogenesis and Management of Sjögren's Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disorder characterized by inflammation and damage to the exocrine glands, leading to symptoms such as ocular and oral dryness, and a range of extraglandular manifestations including polyneuropathies, lung and kidney dysfunction, and systemic vasculitis. Although the exact etiology of SS remains unclear, recent research has highlighted the significant role of gut microbiota in its pathogenesis. Alterations in the gut microbiome, known as dysbiosis, have been implicated in the onset and progression of autoimmune diseases, including SS. This review synthesizes current research on the impact of microbiota on SS, focusing on microbial dysbiosis, its impact on disease severity, and potential therapeutic interventions. Evidence indicates that specific microbial changes, such as reductions in beneficial bacteria and alterations in short-chain fatty acid (SCFA) production, correlate with increased disease activity and systemic inflammation. Microbiome-targeted therapies, including probiotics, prebiotics, and fecal microbiota transplantation, have shown promise in improving SS symptoms and modulating immune responses. Notably, butyrate and specific probiotic strains have demonstrated potential in reducing inflammation and enhancing salivary flow in preclinical studies. However, further research is needed to validate these findings and assess long-term efficacy. This review underscores the importance of gut microbiota in SS and suggests that microbiome-focused treatments could offer new avenues for managing this condition, improving patient outcomes, and potentially preventing disease onset.

Cushing’s syndrome developing myasthenia gravis with takotsubo cardiomyopathy after adrenalectomy: a case report

BackgroundSeveral cases of autoimmune disease onset after treatment for Cushing’s syndrome have been reported.Case presentationHerein, we report a case of myasthenia gravis crisis in a 51-year-old woman 2 months after adrenalectomy for adrenal Cushing’s syndrome accompanied by takotsubo cardiomyopathy. The resolution of excessive endogenous cortisol after adrenalectomy may have triggered the onset of previously latent myasthenia gravis.ConclusionsObserving the similarities in symptoms between myasthenia gravis and adrenal crisis, which can sometimes be challenging to differentiate, is essential. Moreover, the presence of takotsubo cardiomyopathy as a non-motor manifestation of myasthenic crisis must be noted.

Thyroid autoimmunity is associated with dietary fat consumption.

Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

Autoimmune Diseases Following Environmental Disasters: A Narrative Review of the Literature.

Environmental disasters are extreme environmental processes such as earthquakes, volcanic eruptions, landslides, tsunamis, floods, cyclones, storms, wildfires and droughts that are the consequences of the climate crisis due to human intervention in the environment. Their effects on human health have alarmed the global scientific community. Among them, autoimmune diseases, a heterogeneous group of disorders, have increased dramatically in many parts of the world, likely as a result of changes in our exposure to environmental factors. However, only a limited number of studies have attempted to discover and analyze the complex association between environmental disasters and autoimmune diseases. This narrative review has therefore tried to fill this gap. First of all, the activation pathways of autoimmunity after environmental disasters have been analyzed. It has also been shown that wildfires, earthquakes, desert dust storms and volcanic eruptions may damage human health and induce autoimmune responses to inhaled PM2.5, mainly through oxidative stress pathways, increased pro-inflammatory cytokines and epithelial barrier damage. In addition, it has been shown that heat stress, in addition to increasing pro-inflammatory cytokines, may also disrupt the intestinal barrier, thereby increasing its permeability to toxins and pathogens or inducing epigenetic changes. In addition, toxic volcanic elements may accelerate the progressive destruction of myelin, which may potentially trigger multiple sclerosis. The complex and diverse mechanisms by which vector-borne, water-, food-, and rodent-borne diseases that often follow environmental diseases may also trigger autoimmune responses have also been described. In addition, the association between post-disaster stress and the onset or worsening of autoimmune disease has been demonstrated. Given all of the above, the rapid restoration of post-disaster health services to mitigate the flare-up of autoimmune conditions is critical.

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study

Aim of the studyThe primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. Material and methodsWe retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. ResultsPatients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16–30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). ConclusionsWe found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16–30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

The dark side of herbal medicine - risks of Ashwagandha (Withania Somnifera) consumption

Introduction: Herbal medicine has been growing in popularity over the last few years. One of the most often used herbal remedy is Withania somnifera, more widely known as Ashwagandha Now known for its anti-stress, anti-inflammatory, antioxidant, anti-cancer, anti-anxiety properties it ranks as a cure-all. However, there is a rising amount of alarming reports regarding its safety. It has been observed that its effects are not always beneficial, and for some patients the risks of taking it may be greater than the promoted benefits. Aim of study: The aim of this paper is to evaluate possible risks connected to Withania Somnifera consumption based on available research articles and case reports. Materials and methods: This article is based on the literature found in the PubMed Database from the period of 2004-2024 with the use of keywords such as “Ashwagandha”; “Withania Somnifera”, “herbal medicine”;”complementary medicine”;“liver injury”; “thyrotoxicosis”; “adrenal insufficiency”;”autoimmune diseases”. Results: The outcomes of all the reviewed studies in this paper indicate that Withania Somnifera might cause a wide range of side effects. They include herb induced liver injury, endocrine complications such as thyrotoxicosis and adrenal insufficiency, acute graft rejection in a kidney transplant recipient and possible contribution to the onset of new autoimmune disease in patient with the history of autoimmune disorders. Conclusion: Further long-term research is needed on the Ashwaghanda’s benefits but particularly on its safety and potential side effects. The common education on the risks of taking herbal supplements should be carried out among health professionals and the rest of the society. Ashwagandha should not be used by patients with liver, endocrine and autoimmune disorders as well as transplant recipients.

Emerging role of gut microbiota in autoimmune diseases.

Accumulating studies have indicated that the gut microbiota plays a pivotal role in the onset of autoimmune diseases by engaging in complex interactions with the host. This review aims to provide a comprehensive overview of the existing literatures concerning the relationship between the gut microbiota and autoimmune diseases, shedding light on the complex interplay between the gut microbiota, the host and the immune system. Furthermore, we aim to summarize the impacts and potential mechanisms that underlie the interactions between the gut microbiota and the host in autoimmune diseases, primarily focusing on systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, type 1 diabetes mellitus, ulcerative colitis and psoriasis. The present review will emphasize the clinical significance and potential applications of interventions based on the gut microbiota as innovative adjunctive therapies for autoimmune diseases.

Innovate therapeutic targets for autoimmune diseases: insights from proteome-wide mendelian randomization and Bayesian colocalization

Background Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches. Research design and methods Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein–protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings. Results This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (p = 1.61E − 07). TYMP (p = 6.28E − 06) was identified as a protective factor for ulcerative colitis. For Crohn’s disease, ERAP2 (p = 4.47E − 14), HP (p = 2.08E − 05), and RSPO3 (p = 6.52E − 07), were identified as facilitators, whereas FLRT3 (p = 3.42E − 07) had a protective effect. In rheumatoid arthritis, SWAP70 (p = 3.26E − 10), SIGLEC6 (p = 2.47E − 05), ISG15 (p = 3.69E − 05), and FCRL3 (p = 1.10E − 10) were identified as risk factors. B4GALT1 (p = 6.59E − 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (p = 1.58E − 09) but a risk factor for T1D (p = 7.36E − 11), respectively. External validation supported the associations of eight of these proteins with three ADs. Conclusions Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.

Theoretical Studies of DNA Microarray Present Potential Molecular and Cellular Interconnectivity of Signaling Pathways in Immune System Dysregulation.

Autoimmunity is defined as the inability to regulate immunological activities in the body, especially in response to external triggers, leading to the attack of the tissues and organs of the host. Outcomes include the onset of autoimmune diseases whose effects are primarily due to dysregulated immune responses. In past years, there have been cases that show an increased susceptibility to other autoimmune disorders in patients who are already experiencing the same type of disease. Research in this field has started analyzing the potential molecular and cellular causes of this interconnectedness, bearing in mind the possibility of advancing drugs and therapies for the treatment of autoimmunity. With that, this study aimed to determine the correlation of four autoimmune diseases, which are type 1 diabetes (T1D), psoriasis (PSR), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE), by identifying highly preserved co-expressed genes among datasets using WGCNA. Functional annotation was then employed to characterize these sets of genes based on their systemic relationship as a whole to elucidate the biological processes, cellular components, and molecular functions of the pathways they are involved in. Lastly, drug repurposing analysis was performed to screen candidate drugs for repositioning that could regulate the abnormal expression of genes among the diseases. A total of thirteen modules were obtained from the analysis, the majority of which were associated with transcriptional, post-transcriptional, and post-translational modification processes. Also, the evaluation based on KEGG suggested the possible role of TH17 differentiation in the simultaneous onset of the four diseases. Furthermore, clomiphene was the top drug candidate for regulating overexpressed hub genes; meanwhile, prilocaine was the top drug for regulating under-expressed hub genes. This study was geared towards utilizing transcriptomics approaches for the assessment of microarray data, which is different from the use of traditional genomic analyses. Such a research design for investigating correlations among autoimmune diseases may be the first of its kind.

Helicobacter pylori in Inflammatory Bowel Diseases: Active Protagonist or Innocent Bystander?

Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium's presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori's capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs.

Eukaryotes may play an important ecological role in the gut microbiome of Graves' disease.

The prevalence of autoimmune diseases worldwide has risen rapidly over the past few decades. Increasing evidence has linked gut dysbiosis to the onset of various autoimmune diseases. Thanks to the significant advancements in high-throughput sequencing technology, the number of gut microbiome studies has increased. However, they have primarily focused on bacteria, so our understanding of the role and significance of eukaryotic microbes in the human gut microbial ecosystem remains quite limited. Here, we selected Graves' disease (GD) as an autoimmune disease model and investigated the gut multi-kingdom (bacteria, fungi, and protists) microbial communities from the health control, diseased, and medication-treated recovered patients. The results showed that physiological changes in GD increased homogenizing dispersal processes for bacterial community assembly and increased homogeneous selection processes for eukaryotic community assembly. The recovered patients vs. healthy controls had similar bacterial and protistan, but not fungal, community assembly processes. Additionally, eukaryotes (fungi and protists) may play a more significant role in gut ecosystem functions than bacteria. Overall, this study gives brief insights into the potential contributions of eukaryotes to gut and immune homeostasis in humans and their potential influence in relation to therapeutic interventions.

Molecular Characterization of the Recombinant Ig1 Axl Receptor Domain: An Intriguing Bait for Screening in Drug Discovery.

Axl receptor tyrosine kinase and its ligand Gas6 regulate several biological processes and are involved in both the onset and progression of tumor malignancies and autoimmune diseases. Based on its key role in these settings, Axl is considered a promising target for the development of molecules with therapeutic and diagnostic purposes. In this paper, we describe the molecular characterization of the recombinant Ig1 domain of Axl (Ig1 Axl) and its biochemical properties. For the first time, an exhaustive spectroscopic characterization of the recombinant protein through circular dichroism and fluorescence studies is also reported, as well as a binding analysis to its natural ligand Gas6, paving the way for the use of recombinant Ig1 Axl as a bait in drug discovery screening procedures aimed at the identification of novel and specific binders targeting the Axl receptor.

Antithyroid antibody profile and viral markers in autoimmune thyroiditis in Chennai population

Autoimmune thyroid disease (AITD) is the result of a complex interaction between genetic and environmental factors, which leads to failure of one or more mechanisms responsible for controlling thyroid-reactive T and B cells. The most frequently occurring clinical forms of autoimmune thyroiditis include Hashimoto’s thyroiditis and Grave’s disease. Viruses have been implicated in the onset of autoimmune disorders. This study aims to investigate the association between and in autoimmune thyroiditis by assessing virologic and immunologic parameters of cases with clinical indication of AITD. Anti-thyroid peroxidase (TPO) and Anti-thyroglobulin (TG) antibodies were evaluated using ELISA. The presence of Hepatitis C virus (HCV) IgG antibodies and IgM antibodies were evaluated using ELISA. The presence of RNA was investigated by RT-PCR. A total of sixty study subjects were involved in this study. Sixteen male patients (26.66%) and forty-four female patients (68.33%) were positive for Anti-TPO antibodies. Four male patients (6.66%) and twenty-five female patients (41.66%) were positive for Anti-TG antibodies. Four male patients (6.66%) and twenty-two female patients (36.66%) were positive for both Anti-TPO and Anti-TG antibodies. One female patient tested positive for HCV IgG antibodies. Sixteen patients (26.66%) were positive for IgM by ELISA of which 3 patients (5%) were male and 13 patients (21.66%) were female. None of the samples were positive for RNA. We conclude that viral infection may be involved in triggering autoimmune mechanisms. Further studies with a larger population are necessary to establish an association between HCV, and in the pathogenesis of autoimmune thyroid disorders.

Vitamin D and immune system.

The active metabolite of vitamin D 1,25(OH)2D is well known for its role in regulating calcium-phosphate homeostasis of the human body. However, the immunomodulating activity of 1,25(OH)2D has been known for many years. There are numerous reports correlating low vitamin D levels in blood serum with the onset of autoimmune diseases and with the severe course of acute infections. In this chapter, we address the role of 1,25(OH)2D in these diseases, and we discuss the possible mechanisms of action of 1,25(OH)2D in immune cells.

Evaluation of Mitochondrial Respiratory Function in Murine Splenocytes.

Accumulated evidence has demonstrated a key role of mitochondria in the onset and progression of autoimmune disease. Understanding and modulation of mitochondrial dysfunction could provide new molecular targets for both preventive and therapeutic intervention in disease management. The ability to assess mitochondrial function has enabled rheumatologists to advance the understanding of the contribution of cellular metabolism in cellular physiology and disease pathology and etiology. Direct measurement of oxygen consumption rate using an Agilent Seahorse XF measurement system has been widely used as the gold-standard assay for evaluating mitochondrial function in cells. Using this assay system, measurement of parameters of basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and nonmitochondrial respiration can be achieved. An optimized method which works well in mouse splenocytes and a Jurkat cell line is presented in this chapter.