ABSTRACT
Immune checkpoint inhibitors (ICIs) have been widely used as standard therapies for various cancers. However, in 20-30% of cases, ICIs can lead to immune-related adverse events (irAEs), which sometimes require discontinuation of treatment. Due to the increased risk of irAEs, patients with pre-existing autoimmune diseases (AI) are often advised against receiving ICIs. However, there has not been sufficient objective risk assessment for AI. In our study, we conducted logistic regression analysis to assess the risk of irAEs by analyzing 478 cases that received anti-PD-(L)1 Ab and/or anti-CTLA4 Ab at our hospital between April 3, 2017, and May 24, 2022. Among these cases, 28 (5.9%) had pre-existing AI. We selected several independent factors for analysis: gender, age, performance status (PS), cancer type, type of ICI, type of combined anti-cancer agents, best overall response, and pre-existing AI. The adjusted odds ratio (OR) of AI for irAE occurrence was 2.52 [95% CI: 1.08-5.86] (p = 0.033), and the adjusted OR of AI for ICI discontinuation due to irAE was 3.32 [1.41-7.78] (p = 0.006). Patients with pre-existing AI experienced a significantly shorter irAE-free survival time compared to those without AI (median irAE-free survival: 5.7 months [95% CI: 3.5-7.8] vs 10.4 months [95% CI: 7.9-12.9], respectively, p = 0.035). Frequently observed irAEs in full ICI cohort, such as dermatologic issues (7.5%), pneumonitis (7.1%), hepatitis (4.6%), and hypothyroidism (4.2%), were often accompanied by pre-existing AI. Furthermore, pre-existing AI flared up in 6 cases (37.5% in AI-positive irAE-positive cases). The activity of AI was not related to the occurrence of irAEs. Grade 3 or higher irAEs were observed in 6 out of 20 (30.0%) cases in AI-accompanied patients complicated with irAEs. Although having a complicated AI increases the risk of irAEs, it may not necessarily be a contraindication for ICI treatment if closely monitored. (292<300 characters).
Subject(s)
Autoimmune Diseases , Immune Checkpoint Inhibitors , Neoplasms , Humans , Male , Female , Immune Checkpoint Inhibitors/adverse effects , Autoimmune Diseases/chemically induced , Neoplasms/drug therapy , Aged , Middle Aged , Risk Factors , Adult , Aged, 80 and over , Retrospective Studies , CTLA-4 Antigen/antagonists & inhibitorsABSTRACT
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process. METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice. RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet. CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.
Subject(s)
Alcohol Drinking , Autoimmune Diseases , Cell Differentiation , Cholesterol , Disease Models, Animal , Gastrointestinal Microbiome , Mice, Inbred C57BL , Prostatitis , Th17 Cells , Animals , Male , Th17 Cells/immunology , Prostatitis/immunology , Prostatitis/microbiology , Prostatitis/metabolism , Prostatitis/chemically induced , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Autoimmune Diseases/immunology , Autoimmune Diseases/chemically induced , Mice , Cell Differentiation/drug effects , Alcohol Drinking/adverse effects , Cholesterol/metabolism , Sterol Regulatory Element Binding Protein 2/metabolism , Sterol Regulatory Element Binding Protein 2/geneticsSubject(s)
Autoimmune Diseases , Methotrexate , Humans , Methotrexate/therapeutic use , Methotrexate/adverse effects , Female , Male , Autoimmune Diseases/drug therapy , Autoimmune Diseases/chemically induced , Middle Aged , Aged , Rheumatic Diseases/drug therapy , Adult , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effectsABSTRACT
BACKGROUND: Insulin autoantibody syndrome (IAS), or Hirata disease, is caused by high concentrations of insulin autoantibodies, which result in spontaneous, mainly post-prandial, hypoglycemic episodes. We report a case of a previously healthy 67-year-old man presenting with recurrent fasting hypoglycemia culminating in a diagnosis of insulin autoimmune syndrome linked to omeprazole and probably spices, namely, coriander, and ginger. CASE PRESENTATION: A previously healthy 67-year-old Sinhalese man presented with recurrent syncopal attacks for 3 months, which were found to be hypoglycemic episodes. He experienced mainly fasting hypoglycemic attacks, at a frequency gradually increasing to daily attacks. His cardiovascular, respiratory, abdominal, and neurologic examinations were normal. He was found to have insulin levels > 6000 mU/L and a post-polyethylene glycol insulin recovery of less than 9.5%. Contrast-enhanced computed tomography of the pancreas was normal. The diagnosis of insulin autoantibody syndrome was confirmed by testing for the insulin autoantibody level, yielding a level of > 300 U/mL. With regard to a possible trigger, he had a history of omeprazole intake for 2 weeks, 4 weeks prior to the onset of symptoms. He also consumed an herbal supplement containing coriander and ginger extracts daily for a period of 1 year, approximately 2 years prior to the onset of hypoglycemic attacks. He was commenced on prednisolone 30 mg daily, and hypoglycemic episodes responded dramatically, and thus he was tapered off corticosteroids. CONCLUSION: Omeprazole-induced insulin autoantibody syndrome is likely in this patient; however, the known hypoglycemic effects of coriander and ginger make it worthwhile to consider a possible association with insulin autoantibody syndrome. In addition, this case report highlights the need to consider insulin autoantibody syndrome even in patients presenting with fasting hypoglycemic attacks.
Subject(s)
Hypoglycemia , Humans , Male , Aged , Hypoglycemia/immunology , Hypoglycemia/chemically induced , Insulin Antibodies/blood , Insulin Antibodies/immunology , Omeprazole/adverse effects , Omeprazole/therapeutic use , Autoimmune Diseases/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/chemically induced , Autoimmune Diseases/diagnosis , Insulin/immunology , Zingiber officinale/adverse effects , Syndrome , Autoantibodies/bloodABSTRACT
BACKGROUND: The long-term use of rituximab (RTX) has been gaining ground in the treatment of systemic autoimmune diseases. The adverse events (AEs) associated with its use different to infections are being reported. METHODS: A cohort of patients with SAIDs treated at a high-complexity center in Cali (southwestern Colombia) with follow-up from January 2008 to December 2022 were examined to search for potential AEs associated with prolonged use of RTX. RESULTS: From 178 patients with long-term use of RTX 3 (1.68%) had lymphadenopathies with lymphoid follicular hyperplasia related to BAFF overexpression, 4 (2.24%) with bronchiectasis, and 4 (2.24%) with lymphoplasmacytic cystitis. CONCLUSION: Bronchiectasis, lymphoid follicular hyperplasia related to BAFF overexpression, and lymphoplasmacytic cystitis may be life-threatening long-term AEs in patients with prolonged use of RTX.
Subject(s)
Autoimmune Diseases , B-Cell Activating Factor , Bronchiectasis , Cystitis , Rheumatic Diseases , Rituximab , Humans , Rituximab/adverse effects , Rituximab/administration & dosage , Female , Male , Middle Aged , Autoimmune Diseases/chemically induced , Autoimmune Diseases/drug therapy , Bronchiectasis/drug therapy , Cystitis/chemically induced , Rheumatic Diseases/drug therapy , Adult , Antirheumatic Agents/adverse effects , Antirheumatic Agents/administration & dosage , Lymphadenopathy/chemically induced , Aged , Retrospective StudiesABSTRACT
ABSTRACT: Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean corrected QT (QTc) interval and odds ratio of prolonged QTc interval in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc (10.29 ms, P = 0.458) among HCQ users compared to non-HCQ users in patients with RA. There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc compared to non-HCQ users (odds ratio 1.57, 95% CI, 1.19, 2.08). The results of this study suggest that clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring for patients on HCQ for the treatment of systemic autoimmune rheumatic diseases.
Subject(s)
Antirheumatic Agents , Arrhythmias, Cardiac , Autoimmune Diseases , Chloroquine , Death, Sudden, Cardiac , Hydroxychloroquine , Rheumatic Diseases , Hydroxychloroquine/adverse effects , Humans , Antirheumatic Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/physiopathology , Chloroquine/adverse effects , Rheumatic Diseases/drug therapy , Rheumatic Diseases/mortality , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/epidemiology , Autoimmune Diseases/chemically induced , Autoimmune Diseases/diagnosis , Autoimmune Diseases/mortality , Autoimmune Diseases/drug therapy , Risk Assessment , Male , Female , Middle Aged , Adult , Risk Factors , Cardiotoxicity , Aged , Heart Rate/drug effects , Young Adult , Treatment Outcome , Action Potentials/drug effects , Adolescent , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/mortalityABSTRACT
Hypoglycemic disorders are rare in persons without diabetes, and clinical evaluation to identify its etiology can be challenging. We present a case of insulin autoimmune syndrome induced by carbimazole in a middle-aged Chinese man with underlying Graves' disease, which was managed conservatively with a combination of dietary modification and alpha-glucosidase inhibitor.
Subject(s)
Antithyroid Agents , Autoimmune Diseases , Carbimazole , Graves Disease , Humans , Male , Autoimmune Diseases/chemically induced , Graves Disease/drug therapy , Graves Disease/immunology , Carbimazole/therapeutic use , Antithyroid Agents/adverse effects , Antithyroid Agents/therapeutic use , Middle Aged , Insulin , Insulin Antibodies/blood , Syndrome , Glycoside Hydrolase Inhibitors/therapeutic use , Glycoside Hydrolase Inhibitors/adverse effectsABSTRACT
Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0-18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of developing autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.
Subject(s)
Drug Hypersensitivity Syndrome , Humans , Drug Hypersensitivity Syndrome/etiology , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/therapy , Child , Adolescent , Child, Preschool , Infant , Risk Factors , Anti-Bacterial Agents/adverse effects , Treatment Outcome , Autoimmune Diseases/chemically induced , Severity of Illness IndexABSTRACT
PURPOSE OF REVIEW: Exposure to many synthetic chemicals has been linked to a variety of adverse human health effects, including autoimmune diseases. In this scoping review, we summarize recent evidence detailing the effects of synthetic environmental chemicals on autoimmune diseases and highlight current research gaps and recommendations for future studies. RECENT FINDINGS: We identified 68 recent publications related to environmental chemical exposures and autoimmune diseases. Most studies evaluated exposure to persistent environmental chemicals and autoimmune conditions including rheumatoid arthritis (RA), systemic lupus (SLE), systemic sclerosis (SSc), and ulcerative colitis (UC) and Crohn's disease. Results of recent original research studies were mixed, and available data for some exposure-outcome associations were particularly limited. PFAS and autoimmune inflammatory bowel diseases (UC and CD) and pesticides and RA appeared to be the most frequently studied exposure-outcome associations among recent publications, despite a historical research focus on solvents. Recent studies have provided additional evidence for the associations of exposure to synthetic chemicals with certain autoimmune conditions. However, impacts on other autoimmune outcomes, particularly less prevalent conditions, remain unclear. Owing to the ubiquitous nature of many of these exposures and their potential impacts on autoimmune risk, additional studies are needed to better evaluate these relationships, particularly for understudied autoimmune conditions. Future research should include larger longitudinal studies and studies among more diverse populations to elucidate the temporal relationships between exposure-outcome pairs and to identify potential population subgroups that may be more adversely impacted by immune modulation caused by exposure to these chemicals.
Subject(s)
Autoimmune Diseases , Environmental Exposure , Environmental Pollutants , Humans , Autoimmune Diseases/chemically induced , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Environmental Pollutants/adverse effectsABSTRACT
Immune checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancer types. Patients with preexisting autoimmune diseases may be vulnerable to underlying disease flare as well as immune-related adverse events from ICIs. There has also been concern that immunosuppression needed to control the autoimmune disease may blunt ICI efficacy. Much of the literature is focused on diverse preexisting autoimmune diseases, which may limit conclusions to specific diseases. There is a growing literature of specific diseases, such as preexisting rheumatoid arthritis, investigating outcomes after ICI.
Subject(s)
Autoimmune Diseases , Disease Progression , Immune Checkpoint Inhibitors , Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/immunology , Neoplasms/drug therapy , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/chemically induced , Symptom Flare UpABSTRACT
BACKGROUND: Prenatal exposure to environmental contaminants is a significant health concern because it has the potential to interfere with host metabolism, leading to adverse health effects in early childhood and later in life. Growing evidence suggests that genetic and environmental factors, as well as their interactions, play a significant role in the development of autoimmune diseases. OBJECTIVE: In this study, we hypothesized that prenatal exposure to environmental contaminants impacts cord serum metabolome and contributes to the development of autoimmune diseases. METHODS: We selected cord serum samples from All Babies in Southeast Sweden (ABIS) general population cohort, from infants who later developed one or more autoimmune-mediated and inflammatory diseases: celiac disease (CD), Crohn's disease (IBD), hypothyroidism (HT), juvenile idiopathic arthritis (JIA), and type 1 diabetes (T1D) (all cases, N = 62), along with matched controls (N = 268). Using integrated exposomics and metabolomics mass spectrometry (MS) based platforms, we determined the levels of environmental contaminants and metabolites. RESULTS: Differences in exposure levels were found between the controls and those who later developed various diseases. High contaminant exposure levels were associated with changes in metabolome, including amino acids and free fatty acids. Specifically, we identified marked associations between metabolite profiles and exposure levels of deoxynivalenol (DON), bisphenol S (BPS), and specific per- and polyfluorinated substances (PFAS). IMPACT STATEMENT: Abnormal metabolism is a common feature preceding several autoimmune and inflammatory diseases. However, few studies compared common and specific metabolic patterns preceding these diseases. Here we hypothesized that exposure to environmental contaminants impacts cord serum metabolome, which may contribute to the development of autoimmune diseases. We found differences in exposure levels between the controls and those who later developed various diseases, and importantly, on the metabolic changes associated with the exposures. High contaminant exposure levels were associated with specific changes in metabolome. Our study suggests that prenatal exposure to specific environmental contaminants alters the cord serum metabolomes, which, in turn, might increase the risk of various immune-mediated diseases.
Subject(s)
Environmental Pollutants , Fetal Blood , Prenatal Exposure Delayed Effects , Humans , Female , Pregnancy , Fetal Blood/chemistry , Sweden , Prenatal Exposure Delayed Effects/blood , Environmental Pollutants/blood , Metabolome/drug effects , Male , Infant, Newborn , Autoimmune Diseases/chemically induced , Autoimmune Diseases/blood , Metabolomics , Adult , Cohort Studies , Environmental Exposure/adverse effects , Case-Control Studies , InfantABSTRACT
Autoimmune responses are characterized by the presence of antibodies and lymphocytes specific to self or so-called autoantigens. Among such autoantigens is DNA; therefore, screening for antibodies recognizing single- and/or double-stranded DNA is commonly used to detect and classify autoimmune diseases. While autoimmunity affects both sexes, females are generally more affected than males, which is recapitulated in some animal models. A variety of factors, including genetic predisposition and the environment, contribute to the development of autoimmune disorders. Since certain drug products may also contribute to the development of autoimmunity, understanding a drug's potential to trigger an autoimmune response is of interest to immunotoxicology. However, models to study autoimmunity are limited, and it is generally agreed that no model can accurately predict autoimmunity in humans. Herein, we present an in vivo protocol utilizing the SJL/J mouse model to study nanoparticles' effects on the development of autoimmune responses. The protocol is adapted from the literature describing the use of this model to study chemically induced lupus.
Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Humans , Male , Mice , Female , Animals , Autoimmunity , Autoimmune Diseases/chemically induced , Autoimmune Diseases/genetics , Autoantigens , Mice, Inbred Strains , DNAABSTRACT
BACKGROUND: There is growing evidence that the coronavirus disease 2019 (COVID-19) vaccination can affect the regulation of the immune system, leading to the development of autoimmune diseases. However, the autoimmune adverse events (AEs) after COVID-19 vaccination remain largely unclear. OBJECTIVE: We sought to investigate the autoimmune AEs after COVID-19 vaccination from a population-based cohort in South Korea. METHODS: A total of 4,203,887 participants, representing 50% of the population residing in Seoul, were recruited from the National Health Insurance Service database and then divided into 2 groups on the basis of COVID-19 vaccination. The cumulative incidence, hazard ratios (HRs), and 95% CIs of autoimmune AEs were assessed following COVID-19 vaccination. RESULTS: The incidence of vitiligo has been observed to be significantly higher in the vaccination group compared with the no vaccination group. The cumulative incidence of vitiligo began to show a significant difference starting 2 weeks after vaccination, and it reached 2.2% in the vaccination group and 0.6% in the no vaccination group by 3 months after COVID-19 vaccination. Vitiligo (HR, 2.714; 95% CI, 1.777-4.146) was an increased risk among autoimmune AEs. Furthermore, the risk of vitiligo was the highest for heterologous vaccination (HR, 3.890; 95% CI, 2.303-6.573) compared with using cDNA vaccine (HR, 2.861; 95% CI, 1.838-4.453) or mRNA vaccine (HR, 2.475; 95% CI, 1.607-3.813). CONCLUSIONS: Vitiligo as an autoimmune AE was noted to be substantially higher in the COVID-19-vaccinated group compared with the controls. Therefore, the occurrence of vitiligo could be considered as one of the significant AEs post-COVID-19 vaccination.
Subject(s)
Autoimmune Diseases , COVID-19 Vaccines , COVID-19 , Vitiligo , Adult , Aged , Female , Humans , Male , Middle Aged , Autoimmune Diseases/chemically induced , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Incidence , Republic of Korea/epidemiology , Seoul/epidemiology , Vaccination/adverse effects , Vitiligo/chemically inducedABSTRACT
Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant associated with CD4+ T-cell activation and autoimmune disease. Prior studies showed that exposure to TCE in the drinking water of autoimmune-prone mice expanded effector/memory CD4+ T cells with an interferon-γ (IFN-γ)-secreting Th1-like phenotype. However, very little is known how TCE exposure skews CD4+ T cells towards this pro-inflammatory Th1 subset. As observed previously, TCE exposure was associated with hypermethylation of regions of the genome related to transcriptional repression in purified effector/memory CD4 T cells. We hypothesized that TCE modulates transcriptional and/or epigenetic programming of CD4+ T cells as they differentiate from a naive to effector phenotype. In the current study, purified naive CD4 T cells from both male and female autoimmune-prone MRL/MpJ mice were activated ex vivo and polarized towards a Th1 subset for 4 days in the presence or absence of the oxidative metabolite of TCE, trichloroacetaldehyde hydrate (TCAH) in vitro. An RNA-seq assessment and reduced representation bisulfite sequencing for DNA methylation were conducted on Th1 cells or activated, non-polarized cells. The results demonstrated TCAH's ability to regulate key genes involved in the immune response and autoimmunity, including Ifng, by altering the level of DNA methylation at the gene promoter. Intriguing sex differences were observed and for the most part, the effects were more robust in females compared to males. In conclusion, TCE via TCAH epigenetically regulates gene expression in CD4+ T cells. These results may have implications for mechanistic understanding or future therapeutics for autoimmunity.
Subject(s)
DNA Methylation , Th1 Cells , Trichloroethylene , Animals , Trichloroethylene/toxicity , DNA Methylation/drug effects , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Female , Male , Mice , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Mice, Inbred MRL lpr , Gene Expression Regulation/drug effects , Interferon-gamma/metabolism , Autoimmune Diseases/immunology , Autoimmune Diseases/chemically induced , Autoimmune Diseases/genetics , Epigenesis, Genetic/drug effects , Autoimmunity/drug effectsABSTRACT
PURPOSE: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. METHODS: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. RESULTS: Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. CONCLUSION: Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.
Subject(s)
Autoimmune Diseases , Bone Density Conservation Agents , Bone Density , Glucocorticoids , Osteoporosis , Patient Preference , Zoledronic Acid , Humans , Zoledronic Acid/therapeutic use , Zoledronic Acid/adverse effects , Osteoporosis/drug therapy , Osteoporosis/chemically induced , Female , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Male , Bone Density Conservation Agents/therapeutic use , Bone Density Conservation Agents/adverse effects , Autoimmune Diseases/drug therapy , Autoimmune Diseases/chemically induced , Middle Aged , Bone Density/drug effects , Aged , Administration, Oral , Diphosphonates/therapeutic use , Diphosphonates/adverse effects , Diphosphonates/administration & dosage , Patient Satisfaction , Treatment Outcome , Imidazoles/adverse effects , Imidazoles/therapeutic use , Imidazoles/administration & dosageABSTRACT
Background and Objectives: Rituximab (RTX) has been the predominant treatment for autoimmune bullous diseases (AIBDs). The objective of this research was to assess the advantages and safety characteristics of RTX treatment in individuals with AIBD. This assessment focused on clinical remission and a reduction in glucocorticosteroid usage, its effect on the titers of autoantibodies targeting desmoglein-1 (DSG-1) and desmoglein-3 (DSG-3), and adverse occurrences during a 12-month follow-up period in a dermatology department within a Central European university context. Materials and Methods: Our case series involved eleven patients, including eight patients with pemphigus vulgaris, two with pemphigus foliaceus, and one with epidermolysis bullosa acquisita. They received a 1 g dose of rituximab, repeated over a two-week interval. Results: The reduction in a prednisone-equivalent dosage after 2, 6, and 12 months following the second RTX infusion was 65.05%, 73.99%, and 76.93%, in that order. The titers of antibodies against DSG-1 exhibited reductions of 43.29%, 75.86%, and 54.02% at 2, 6, and 12 months, respectively. By contrast, the antibody concentrations targeting DSG-3 displayed a decrease of 27.88%, 14.48%, and 5.09% at the corresponding time points. Over the course of the 12-month monitoring period, 18.18% of patients experienced disease relapse, while the remaining individuals achieved either complete or partial remission with minimal or no therapy. Adverse effects were noted in 36.36% of the patient population; they were mild, and no serious adverse effects were reported. Conclusions: RTX represents an efficacious and well-tolerated therapeutic option for the management of AIBD and merits consideration in cases of refractory AIBD. However, further research is imperative to delineate the most optimal dosage, dosing frequency, and total quantity of maintenance infusions required. Additionally, there is a compelling need for studies that explore the impact of RTX on individuals with AIBD who do not exhibit a significant reduction in anti-desmoglein autoantibody levels.
Subject(s)
Autoimmune Diseases , Pemphigus , Humans , Rituximab/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/chemically induced , Pemphigus/drug therapy , Autoantibodies , Desmogleins , Retrospective StudiesABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD). OBJECTIVES: The aim of this study was to characterize MDs occurring as immune-related adverse events (irAEs) of ICIs. METHODS: A systematic literature review of case reports/series of MDs as irAEs of ICIs was performed. RESULTS: Of 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course. CONCLUSION: MDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment.
Subject(s)
Immune Checkpoint Inhibitors , Movement Disorders , Humans , Immune Checkpoint Inhibitors/adverse effects , Movement Disorders/etiology , Autoimmune Diseases/chemically induced , Autoimmune Diseases/drug therapy , Immunotherapy/adverse effects , Neoplasms/drug therapy , Neoplasms/complicationsABSTRACT
PURPOSE: Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. METHODS: We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). RESULTS: We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. CONCLUSION: In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.
Subject(s)
Autoimmune Diseases , COVID-19 , Humans , COVID-19 Vaccines/adverse effects , Pharmacovigilance , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination/adverse effects , Autoimmune Diseases/chemically induced , Autoimmune Diseases/epidemiology , Adverse Drug Reaction Reporting SystemsABSTRACT
OBJECTIVES: To evaluate adherence to medication in patients with systemic autoimmune diseases (SAD), comparing pregnant and non-pregnant women. METHODS: 200 patients with SAD were consecutively enrolled, 100 pregnant and 100 non-pregnant women. Each patient completed the 8-item Morisky Medication Adherence Scale (MMAS-8), one copy for hydroxychloroquine (HCQ) and one for other treatments for rheumatic disease, and Hospital Anxiety and Depression Scale (HADS). RESULTS: No significant differences were found in ongoing therapies between pregnant and non-pregnant women. 148 patients (74.0%) were taking HCQ and 160 (80.0%) other therapies for rheumatic disease. The mean MMAS-8 score was >6 in all groups indicating a good adherence, on average. The rate of patients with good medication adherence was higher in pregnant patients (73.9% vs. 63.3% and 76.5% vs. 64.5%, for HCQ and other therapies, respectively) although this difference was not statistically significant. Eight patients had very poor medical adherence, and all were non-pregnant women. Anxiety (15% of patients) was associated to low medication adherence for drugs other than HCQ (p=0.02), while depression (4% of patients) did not seem to have an impact on adherence. CONCLUSIONS: In our cohort we recorded a good adherence to prescribed medication, although adequate adherence was not achieved in about 30% of patients, confirming that non-adherence is an important issue in SAD. It is difficult to define a profile of patients at risk of poor adherence, but it appears important to implement communication and adherence monitoring strategies since strict monitoring also during pregnancy could improve medical adherence.