Search Results (43)

Killer Ig-like Receptors (KIRs) regulate immune responses, maintaining the balance between activation and inhibition of the immune system. KIRs are expressed on natural killer cells and some CD8 T cells and interact with HLA class I molecules, influencing various physiological and pathological processes. KIRs’ polymorphism creates a variability in immune responses among individuals. KIRs are involved in autoimmune disorders, cancer, infections, neurological diseases, and other diseases. Specific combinations of KIRs and HLA are linked to several diseases’ susceptibility, progression, and outcomes. In particular, the balance between inhibitory and activating KIRs can determine how the immune system responds to pathogens and tumors. An imbalance can lead to an excessive response, contributing to autoimmune diseases, or an inadequate response, allowing immune evasion by pathogens or cancer cells. The increasing number of studies on KIRs highlights their essential role as diagnostic and prognostic biomarkers and potential therapeutic targets. This review provides a comprehensive overview of the role of KIRs in all clinical conditions and diseases, listed alphabetically, where they are analyzed. Full article

The genetic landscape of multiple sclerosis (MS) has been extensively mapped, yielding significant insights into the molecular mechanisms of the disorder. Early studies highlighted key genes associated with the immune system, particularly T cells, as critical for MS susceptibility. Subsequent large-scale genome-wide association studies (GWASs) identified over 200 genetic variants linked to MS, revealing a complex interplay between MS risk and genes involved in various processes within adaptive and innate immune cells, as well as brain-resident microglia. Recently, a groundbreaking GWAS pinpointed the first gene variant associated with MS disease progression, distinguishing the mechanisms driving disease onset from those influencing progression. The C-type lectin domain family 16, member A (CLEC16A) gene within the 16p13 region has consistently been shown to be associated with increased risk of developing both MS and other autoimmune disorders. Notably, several autoimmune-associated genetic variants in CLEC16A introns act as expression quantitative trait loci for the dexamethasone-induced protein (DEXI gene, adding DEXI to the growing list of MS susceptibility genes. This review explores the molecular and functional characterization of DEXI with a particular focus on recent advances in understanding its role in autoimmunity, specifically in the context of multiple sclerosis. We underscore the importance of continued molecular investigation of susceptibility loci for MS identified in genetic studies, with the goal of translating this knowledge into clinical applications. Full article

Background/Objectives: In Sjögren’s syndrome, exocrine glands are destructed in an autoimmune-mediated process. Obesity is known to influence a wide range of diseases. This study aimed to examine whether obesity has an impact on the disease course of our patients with Sjögren’s syndrome. Methods: Out of the regularly followed-up patients, 125 were grouped based on their body mass index (BMI). Below a BMI of 25, they were listed as “non-obese” (n = 45), whereas above a BMI of 25, they were categorized as “obese” (n = 80). Demographic, laboratory, and immunological parameters; Sjögren’s syndrome disease activity index; certain extraglandular manifestations; and treatment modalities were compared using biostatistical methods. Results: Among the examined cardiovascular and cerebrovascular co-morbidities, type 2 diabetes and hypertension were significantly more frequent in the obese group. Considering the associated further autoimmune disorders and extraglandular manifestations, in our patients, there were no significant differences between the two groups. Among laboratory parameters, gamma glutamil transferase, alanine transaminase, hemoglobin, hematocrit, lymphocyte rate, triglyceride, and c3 and c4 complement levels were significantly higher in the obese group, while the proportion of rheumatoid factor positivity and the neutrophil granulocyte rate were significantly lower. Immunoglobulin G, A, and M levels did not differ significantly between the two subsets. Obese patients needed steroid therapy significantly less frequently; however, statin therapy was remarkably more frequent in that group. Furthermore, the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) was significantly lower in the group of overweight patients. Conclusions: Our results suggest that several immunological parameters of obese patients are more favorable compared to those with normal body weight. Behind that, we might suspect either the beneficial effect of statin therapy and/or the obesity paradox. Full article

The failure of immunotherapies in cancer patients is being widely studied due to the complexities present in the tumor microenvironment (TME), where regulatory T cells (Treg) appear to actively participate in providing an immune escape mechanism for tumors. Therefore, therapies to specifically inhibit tumor-infiltrating Treg represent a challenge, because Treg are distributed throughout the body and provide physiological immune homeostasis to prevent autoimmune diseases. Characterization of immunological and functional profiles could help to identify the mechanisms that need to be inhibited or activated to ensure Treg modulation in the tumor. To address this, quantitative in silico approaches based on mechanistic mathematical models integrating multi-scale information from immune and tumor cells and the effect of different therapies have allowed the building of computational frameworks to simulate different hypotheses, some of which have subsequently been experimentally validated. Therefore, this review presents a list of diverse computational mathematical models that examine the role of Treg as a crucial immune resistance mechanism contributing to the failure of immunotherapy. In addition, this review highlights the relevance of certain molecules expressed in Treg that are associated with the TME immunosuppression, which could be incorporated into the mathematical model for a better understanding of the contribution of Treg modulation. Finally, different preclinical and clinical combinations of molecules are also included to show the trend of new therapies targeting Treg. Full article

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: “vitamin D, muscle, rheumatic diseases.” Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold. Full article

Multiple sclerosis is an autoimmune disease that affects the central nervous system. In Brazil, there are currently several therapeutic options for the treatment of this condition, with some being distributed free of charge, while others are not included in the list of free medications. The objective of this article is to provide a pharmacoepidemiological analysis of the available medications in the country, covering their mechanisms of action, the historical context of approval and free distribution within the healthcare system, and their geographical distribution of application. Additionally, we discuss the impact of the inclusion of these medications on hospitalization and mortality rates in the country. We hope that this work serves as a resource for healthcare professionals to better understand pharmacoepidemiology and for health policymakers seeking data for the planning of public policies aimed at the treatment of multiple sclerosis. Full article

Interstitial lung disease (ILD), which is characterized by pulmonary fibrosis, is a diverse group of disorders. Nintedanib, an antifibrotic drug, is known to attenuate disease progression in ILD with progressive fibrosis, but its efficacy in autoimmune-disease-related ILD remains uncertain. We conducted a comprehensive search for relevant randomized controlled trials, systematic reviews and meta-analyses included in PubMed, ScienceDirect and Scopus databases as of 23 June 2022 and manually reviewed reference lists. Among the 689 titles and abstracts screened, 24 studies were considered, with 4 randomized controlled trials included in our review. Nintedanib, administered at 150 mg twice daily for 52 weeks, consistently slowed forced vital capacity decline. Enhanced efficacy was observed when combining nintedanib with immunomodulators, and the most common adverse effect was diarrhea. In conclusion, our study suggests that nintedanib is a safe option for mitigating the progression of autoimmune-disease-related ILD, providing valuable insights into its potential therapeutic role in this context. Full article

Neutrophils are the principal trouper of the innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host’s protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including the promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, and cancer diseases, and the list is increasing gradually. In this review, we summarize the NET-mediated pathophysiology of different diseases and focus on some updated potential therapeutic approaches against NETs. Full article

Background: First episode of psychosis (FEP) is a clinical condition that usually occurs during adolescence or early adulthood and is often a sign of a future psychiatric disease. However, these symptoms are not specific, and psychosis can be caused by a physical disease in at least 5% of cases. Timely detection of these diseases, the first signs of which may appear in childhood, is of particular importance, as a curable treatment exists in most cases. However, there is no consensus in academic societies to offer recommendations for a comprehensive medical assessment to eliminate somatic causes. Methods: We conducted a systematic literature search using a two-fold research strategy to: (1) identify physical diseases that can be differentially diagnosed for psychosis; and (2) determine the paraclinical exams allowing us to exclude these pathologies. Results: We identified 85 articles describing the autoimmune, metabolic, neurologic, infectious, and genetic differential diagnoses of psychosis. Clinical presentations are described, and a complete list of laboratory and imaging features required to identify and confirm these diseases is provided. Conclusion: This systematic review shows that most differential diagnoses of psychosis should be considered in the case of a FEP and could be identified by providing a systematic checkup with a laboratory test that includes ammonemia, antinuclear and anti-NMDA antibodies, and HIV testing; brain magnetic resonance imaging and lumbar puncture should be considered according to the clinical presentation. Genetic research could be of interest to patients presenting with physical or developmental symptoms associated with psychiatric manifestations. Full article

The increasing morbidity and mortality of life-threatening Pneumocystis pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP. Full article

As COVID-19 vaccination guidelines were issued by Advisory Committee on Immunization Practices (ACIP) and the Centers for Diseases Control and Prevention (CDC) across the US, each state and clinical provider instituted vaccine implementation and education policies and protocols for high-risk populations. However, current research has shown that while people with autoimmune diseases were listed by ACIP and CDC as a COVID-19 high-risk population, the rate of adherence to implementation and education protocols, as well as the prioritization of this sub-population as a high-risk group, varied among the clinicians and vaccinators thus impacting the hesitancy towards the COVID-19 vaccine and a correlation to low vaccination rates. The purpose of this review was to explore factors of COVID-19 vaccination hesitancy in people living with autoimmune diseases in relation to current implementation and education policies and protocols, as well as ethical and contextual factors, while providing possible implications. COVID-19 vaccine hesitancy in people living with autoimmune disease was greater than in the general population, as demonstrated by increased levels of overall mistrust and fear of potential risk and harmful side effects. Evidence has shown that COVID-19 vaccination is safe and effective for patients with autoimmune diseases. Additionally, the benefits of COVID-19 vaccination outweigh its potential risks and adverse effects in this population. However, the non-adherence to policy and protocols, especially community education protocols, by those providing the vaccination have a negative impact on the overall perception of the vaccine and needs to be addressed at local and state levels in order to protect this population. Future research should provide strategies to guide collaborative efforts between government and local agencies in providing tailored vaccination campaigns to this population. In parallel with policy, COVID-19 vaccination intervention implementation and educational protocols should be developed with evidence-based guidelines for public health and clinical professionals that are targeted at this vulnerable high-risk population. Full article

Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient’s demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5–5.2) years; a total of 66 (40.7%) of these patients initially presented with these manifestations. Patients with cutaneous involvement were generally older at the time of diagnosis [5.0 (1.6–8.0) vs. 3.0 (1.0–7.0) years; p = 0.022]. Consanguinity was more common among patients who developed skin disorders (81.4% vs. 65.2%, p < 0.001). The overall skin infection rate and the type of dominant pathogens were significantly different among the IEI patients in different phenotypical classifications (p < 0.001). Atopic presentation, including urticaria, was highly prevalent among patients with congenital defects of phagocytes (p = 0.020). The frequency of eczema was also significantly higher among cases with both syndromic and non-syndromic combined immunodeficiency (p = 0.009). In contrast, autoimmune cutaneous manifestations, including alopecia and psoriasis, were most common in patients with immune dysregulation (p = 0.001) and defects in intrinsic or innate immunity (p = 0.031), respectively. The presence of autoimmune cutaneous complications significantly improved the survival rate of IEI patients (p = 0.21). In conclusion, cutaneous manifestations were observed in nearly 44% of Iranian patients with monogenic IEI. A considerable number of patients with cutaneous involvements developed these disorders as their first manifestation of the disease, which was particularly noticeable in patients with non-syndromic combined immunodeficiency and phagocytic defects. The neglected skin disorders in IEI patients might delay diagnosis, which is generally established within a 3-year interval from the development of skin-related problems. Cutaneous disorders, especially autoimmune features, might indicate a mild prognosis in IEI patients. Full article

Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires immunosuppression for an extended period. Frequent relapses after treatment discontinuation demonstrate that current therapies do not control intrahepatic immune processes. This study describes targeted proteomic profiling data in patients with AIH and controls. A total of 92 inflammatory and 92 cardiometabolic plasma markers were assessed for (i) pediatric AIH versus controls, (ii) AIH type 1 versus type 2, (iii) AIH and AIH–autoimmune sclerosing cholangitis overlapping syndrome and (iv) correlations with circulating vitamin D levels in AIH. A total of 16 proteins showed a nominally significant differential abundance in pediatric patients with AIH compared to controls. No clustering of AIH subphenotypes based on all protein data was observed, and no significant correlation of vitamin D levels was observed for the identified proteins. The proteins that showed variable expression include CA1, CA3, GAS6, FCGR2A, 4E-BP1 and CCL19, which may serve as potential biomarkers for patients with AIH. CX3CL1, CXCL10, CCL23, CSF1 and CCL19 showed homology to one another and may be coexpressed in AIH. CXCL10 seems to be the central intermediary link for the listed proteins. These proteins were involved in relevant mechanistic pathways for liver diseases and immune processes in AIH pathogenesis. This is the first report on the proteomic profile of pediatric AIH. The identified markers could potentially lead to new diagnostic and therapeutic tools. Nevertheless, considering the complex pathogenesis of AIH, more extensive studies are warranted to replicate and validate the present study’s findings. Full article

Primary (pIgAN), secondary IgA nephropathy (sIgAN), and IgA-associated nephropathy can be distinguished. While pIgAN has been thoroughly studied, information about the etiology of sIgAN remains scarce. As concerns sIgAN, several studies suggest that different etiologic factors play a role and ultimately lead to a pathophysiologic process similar to that of pIgAN. In this article, we review a vast number of cases in order to determine the novel putative underlying diseases of sIgAN. Moreover, updates on the common pathophysiology of primary disorders and sIgAN are presented. We identified liver, gastrointestinal, oncological, dermatological, autoimmune, and respiratory diseases, as well as infectious, iatrogenic, and environmental factors, as triggers of sIgAN. As novel biological therapies for listed underlying diseases emerge, we suggest implementing drug-induced sIgAN as a new significant category. Clinicians should acknowledge the possibility of sIgAN progression in patients treated with TNF-α inhibitors, IL-12/IL-23-inhibitors, immune checkpoint inhibitors, CTLA-4, oral anticoagulants, thioureylene derivatives, and anti-vascular endothelial growth factor drugs. Full article

The aryl hydrocarbon receptor (AHR) is a sensor of low-molecular-weight molecule signals that originate from environmental exposures, the microbiome, and host metabolism. Building upon initial studies examining anthropogenic chemical exposures, the list of AHR ligands of microbial, diet, and host metabolism origin continues to grow and has provided important clues as to the function of this enigmatic receptor. The AHR has now been shown to be directly involved in numerous biochemical pathways that influence host homeostasis, chronic disease development, and responses to toxic insults. As this field of study has continued to grow, it has become apparent that the AHR is an important novel target for cancer, metabolic diseases, skin conditions, and autoimmune disease. This meeting attempted to cover the scope of basic and applied research being performed to address possible applications of our basic knowledge of this receptor on therapeutic outcomes. Full article