Prevalence Of Autoimmune Diseases Research Articles

Nivoi vitamina D i genetski variant VDR rs2228570 u autoimunom tireoditisu

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disorder characterized by an immune response targeting the thyroid gland. Genetic factors play a significant role in AIT susceptibility, with immune-related genes, especially the vitamin D receptor (VDR) gene, potentially influencing AIT development. This comprehensive review delves into the intricate association between VDR gene polymorphisms, particularly rs2228570 (FokI), and AIT susceptibility, exploring various populations. Research has unveiled contrasting outcomes regarding the link between the VDR rs2228570 polymorphism and AIT risk across diverse ethnic groups. Certain populations have exhibited a noteworthy correlation, suggesting that population-specific genetic factors contribute to AIT risk. A recurring observation of vitamin D deficiency in AIT patients has correlated with elevated anti-thyroid antibodies, abnormal thyroid function , and thyroid volume. The results emphasize the possible role of vitamin D in the development of AIT, suggesting the importance of vitamin D supplementation to address deficiencies associated with AIT. In addition to VDR rs2228570, other genetic variants have also shown associations with AIT susceptibility, displaying varying results across different populations. Ethnicity emerges as a pivotal factor influencing these associations, underscoring the need to consider genetic variations in diverse populations. We emphasize the intricate interplay between VDR gene polymorphisms, vitamin D, and AIT susceptibility. Extensive research is essential to unveil the clinical significance of these genetic variations, offering prospects for enhanced diagnostic and therapeutic strategies for individuals with AIT.

Iatrogenic immunodeficiency-associated lymphoproliferative disorders of the central nervous system: a treatment paradox.

Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens. With increasing prevalence of autoimmune disease and development of new immunosuppressants, a genetically distinct entity known as iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD) has emerged. Many of these cases arise following methotrexate use, challenging feasibility of standard HD-MTX regimens. The aim of this study was to further characterize this disorder and determine the optimal management strategy. We describe a case of a 76-year-old female with iatrogenic immunodeficiency-associated PCNSL successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency-associated LPD involving the CNS. We used a linear probability statistical model to determine correlations with outcome. Natalizumab was associated with EBV negative tumors (P=.023), and EBV positive tumors were associated with improved outcomes (P=.016). Surgical resection was associated with improved outcomes (P=.032), although limited by potential confounding effect. Antiviral treatment (P=.095), rituximab (P=.111), and stem cell transplant (SCT) (P=.198) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. We propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency-associated LPD of the CNS. Further study through prospective cohort studies or randomized clinical trials is warranted.

Clinical Value of IL6R Gene Variants as Predictive Biomarkers for Toxicity to Tocilizumab in Patients with Rheumatoid Arthritis.

Tocilizumab is a first-line biologic disease-modifying anti-rheumatic drug (bDMARD) that inhibits the interleukin-6 (IL-6) pathway by antagonizing the IL-6 receptor (IL-6R). Tocilizumab is widely used to treat rheumatoid arthritis (RA), a prevalent autoimmune disease that can cause irreversible joint damage and disability. Although many bDMARDs have been developed for RA, there is a lack of validated biomarkers which could guide personalized medicine strategies. To evaluate whether single-nucleotide polymorphisms (SNPs) in the IL6R gene could predict tocilizumab toxicity in patients with RA, we conducted a retrospective cohort study of 88 patients treated with tocilizumab. Six SNPs previously described in the IL6R gene were genotyped (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625). Using parametric tests, we studied the association between the SNPs and hepatotoxicity, infection, hypersensitivity, gastrointestinal, hematological, and dyslipidemia adverse events (AEs). We found associations between dyslipidemia and rs4845625 and between hematological AEs and rs11265618 and rs4329505. No further associations were found for the remaining SNPs and other AEs. Our findings support the potential clinical value of SNPs in the IL6R gene as predictive biomarkers for toxicity to tocilizumab in patients with RA.

Patterns Of Autoimmune Diseases Among Yemeni Children with Down Syndrome

Background: Down syndrome can be associated with autoimmune diseases such as Celiac disease, autoimmune Thyroiditis, Type 1 DM and other diseases. Aim: The aim of this study was to determine the prevalence of hypothyroidism, Type 1 DM, and Celiac disease in Yemeni children with Down syndrome as well as the most common mother's age for the occurrence of this syndrome. Method: This study was cross-sectional study involving one hundred and six Yemeni children with Down syndrome selected by simple random sampling from Special Needs Centers for Down syndrome in Sana'a city, Yemen, during 2019. These children were investigated for the presence of anti-thyroid peroxidase antibodies, TSH, and T4 for hypothyroidism; random blood sugar, anti-glutamic acid decarboxylase antibodies for Type 1 DM; and antitransglutaminase immunoglobulin A, and G antibodies for Celiac disease. Results: The prevalence of autoimmune diseases in the 106 Yemeni children with Down syndrome was 5.77% hypothyroidism, 2.8% Type 1 DM, and 0.94% Celiac disease. The highest number of Down syndrome babies were born at 41 to 50 years of mother's age. Conclusion: Hypothyroidism was the most prevalent autoimmune disease in Yemeni children with Down syndrome and Celiac disease was the least prevalent. Down syndrome can occur at any maternal age, but may increase with age. Children suffering from Down syndrome should be monitored periodically for autoimmune diseases to make early diagnosis, start early treatment, and decrease the occurrence of complications.

Comparative efficacy and safety of JAK inhibitors and leflunomide in rheumatoid arthritis: A protocol for systematic review and meta-analysis.

Rheumatoid arthritis is the most prevalent systemic autoimmune disease among the rheumatic inflammatory musculoskeletal diseases. Currently, there is no reliable evidence regarding the comparisons of anti-rheumatic effects between leflunomide and Janus kinase inhibitors. We performed a protocol for systematic review and meta-analysis to compare the efficacy and safety of Janus kinase inhibitors and leflunomide in rheumatoid arthritis. This review has been reported following the preferred reporting items for systematic reviews and meta-analyses protocol. We will search 7 electronic databases to identify relevant studies from inception to November, 2022, which includes PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database. Risk of bias will be assessed according to the Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system will be used to judge the overall quality of evidence supporting outcomes in this work. Data analysis was performed using Reviewer Manager 5.4. The results of this systematic review will be published in a peer-reviewed journal. This systematic review will provide evidence to judge whether Janus kinase inhibitors is superior to leflunomide in patients with in rheumatoid arthritis.

Effect of puberty on the immune system: Relevance to multiple sclerosis.

Puberty is a dynamic period marked by changing levels of sex hormones, the development of secondary sexual characteristics and reproductive maturity. This period has profound effects on various organ systems, including the immune system. The critical changes that occur in the immune system during pubertal onset have been shown to have implications for autoimmune conditions, including Multiple Sclerosis (MS). MS is rare prior to puberty but can manifest in children after puberty. This disease also has a clear female preponderance that only arises following pubertal onset, highlighting a potential role for sex hormones in autoimmunity. Early onset of puberty has also been shown to be a risk factor for MS. The purpose of this review is to overview the evidence that puberty regulates MS susceptibility and disease activity. Given that there is a paucity of studies that directly evaluate the effects of puberty on the immune system, we also discuss how the immune system is different in children and mice of pre- vs. post-pubertal ages and describe how gonadal hormones may regulate these immune mechanisms. We present evidence that puberty enhances the expression of co-stimulatory molecules and cytokine production by type 2 dendritic cells (DC2s) and plasmacytoid dendritic cells (pDCs), increases T helper 1 (Th1), Th17, and T follicular helper immunity, and promotes immunoglobulin (Ig)G antibody production. Overall, this review highlights how the immune system undergoes a functional maturation during puberty, which has the potential to explain the higher prevalence of MS and other autoimmune diseases seen in adolescence.

Two-way association between alopecia areata and sleep disorders: A systematic review of observational studies.

Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher risk of developing obstructive sleep apnea and non-apneic insomnia than patients without AA. On the contrary, patients with identified sleep disorders were found to be more prone to developing AA as compared to the patients without sleep disorders. This study, therefore, validated the hypothesis of a bidirectional association between AA and sleep disorders. In this systematic review, our primary aim is to assess the prevalence of sleep disorders in Alopecia Areata patients while also assessing the inverse relationship between the two disorders. A literature search of MEDLINE, Google Scholar and Cochrane CENTRAL was performed from their inception to April 2022. Articles were selected for inclusion if they met the following eligibility criteria: (a) Studies enrolling patients having alopecia areata to assess the sleep quality. (b) Studies assessing the risks of alopecia areata in individuals with sleep disorder (c) Studies evaluating the bidirectional association between alopecia areata and sleep quality. Case reports, commentaries, and editorials were excluded. The outcomes of recruited studies were qualitatively synthesised and study findings are summarized in the results section and tabulated in summary tables. Our search on electronic databases yielded 1562 articles. After abstract screening and full text review, 5 cross sectional and 3 cohort studies are included in this systematic review. Cases with PSQI scores higher than 5 and 6 were found to be in greater numbers amongst the AA patient population when compared to the control population (p<0.001). Moreover, studies showed that patients with sleep disorders were greatly predisposed to develop subsequent AA as compared to patients without sleep disorders (aHR 4.70; 95% CI 3.99-5.54) (P<0.0001). The findings from our results display a significant bi-directional cause-effect relation between AA and sleep disorders. However, more large-scale observational studies on this subject are required to further validate our findings.

Evaluation of IL-10, MCP-1, IFN gamma, and protectin D1 levels in patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is one of the most prevalent autoimmune endocrine diseases and caused by the loss of immune tolerance for the thyroid gland. Many pathophysiological mechanisms were speculated about the development of HT. In our study, we aimed to reveal the relationship between HT and IL-10, MCP-1, IFNɤ, and PD1 levels and compare them with control subjects. We collected 37 patients with HT and 25 controls referred to our outpatient clinic. The diagnosis of HT was based on the detection of circulating antibodies to thyroid antigens and decreasing echogenicity on thyroid USG in patients with appropriate clinical characteristics. Serum IL-10, MCP-1, IFNɤ, and PD1 levels were detected using an ELISA KIT (96T) method according to the manufacturer's instructions. All subjects were euthyroid (median TSH level was 1.68mU/L in HT vs 1.83mU/L in the controls, p = 0.672). Twenty-three of 37 patients with HT were taking L-thyroxin replacement. Levels of serum IL-10, IFNɤ, and PD1 in patients with HT were higher than the controls, but the differences were not statistically significant (p = 0.393, p = 0.495, and p = 0.052 respectively). The serum levels of MCP-1 in HT patients were statistically different and higher than the controls (p = 0.018). Correlation analysis displayed significant associations between IL-10, MCP-1, IFNɤ, and PD1 levels. Our study demonstrated that serum MCP-1 levels in HT patients were significantly increased; on the other hand, significant difference was not found between HT patients and the controls in terms of serum IL-10, IFNɤ, and PD1 levels.

Clinical characteristics of myasthenia gravis (MG) patients developing other autoimmune diseases after thymectomy from one single center cohort.

Myasthenia gravis (MG) patients are reported to have a high risk of other autoimmune diseases (ADs), and thymectomy may increase the risk further. A cohort of MG patients in which thymectomy was performed were investigated to analyze the prevalence, types and features of the new onset ADs. Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Patients with a postoperative follow-up period shorter than a year or incomplete clinical records were excluded. Clinical and follow-up data were collected. Statistical analyses were performed using SPSS version 22.0. A total of 445 patients were included in this study. The median follow-up period was 72 months (range, 12-135 months). A total of 63 (14.2%) MG patients had concurrent ADs. The incidence rate was higher than the background prevalence of population (5%), and also higher than that of a former Chinese MG cohort (11.6%). A total of 47 patients (10.6%) were diagnosed with ADs before thymectomy, and 19 (4.3%) developed a new AD after thymectomy. The most common types of new onset ADs after thymectomy were Hashimoto's thyroiditis and rheumatoid arthritis (RA), which were different from those before thymectomy (hyperthyroidism and Hashimoto's thyroiditis). The incidence rate of new onset RA (1.35%) was higher than the frequency of RA before thymectomy (0.45%), and also higher than the incidence rate in a Chinese MG cohort (0.5%). There was a higher proportion of female patients (p= 0.026) with postoperative ADs. A younger age at operation may increase the risk of nonthymoma MG patients (p= 0.040) developing ADs. The postoperative treatment effect of MG was similar between patients with and without new onset ADs (p> 0.05). We observed a higher incidence rate of autoimmune diseases, especially rheumatoid arthritis, in MG patients after thymectomy. The most common types of ADs after thymectomy were different from those before thymectomy. New onset ADs tended to occur in female and young nonthymoma MG patients. The postoperative effect of MG was not related with the new occurrence of ADs.

Prevalence of familial autoimmune diseases in juvenile idiopathic arthritis: results from the international Pharmachild registry

BackgroundLittle is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA).MethodsPrevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using χ2 and Mann-Whitney U tests.ResultsEight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P < 0.01), Scandinavian residence (P < 0.01), enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (P < 0.01), ANA positivity (P = 0.03) and HLA-B27 positivity (P < 0.01).ConclusionsFamilial AD proves to be a risk factor for JIA development and certain diseases should therefore not be overlooked during family health history at the diagnosis stage. A family history of AD is associated with the JIA category but does not influence the severity or disease course.

Autoimmune Diseases Are Not Associated with Monoclonal Gammopathy of Undetermined Significance: Results of the Prospective Population-Based Istopmm Study

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma and related conditions. Previous registry-based studies and retrospective clinical case studies have proposed an increased risk of MGUS among patients with autoimmune diseases. However, as the clinical diagnosis of MGUS is, by definition, made when investigating the cause of unrelated symptoms, prior studies have been unable to control for selection bias. Therefore, the true relationship between MGUS and autoimmune diseases remains unknown and can only be evaluated in a screening study. Aims: To examine whether autoimmune diseases are associated with MGUS in a screened population. Methods: This study used data from Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM), a population-based screening study of MGUS. Briefly, 93% of 80,759 consented participants, representing 54% of the Icelandic population aged 40 years or older, have been screened for MGUS using serum protein electrophoresis (SPEP) and a free light chain (FLC) assay. To identify individuals in the study with a previous clinical diagnosis of MGUS, records from the two laboratories performing SPEP in Iceland were used and cross referenced with the Icelandic Cancer Registry. Diagnoses of autoimmune diseases were extracted from the Icelandic Hospital Discharge Register and the Icelandic Register of Primary Health Care Contacts, both of which have >95% completeness and accuracy. All diagnoses from the 1st of January 1999 to 31st of December 2020 were included. T-test and chi-squared test were used for univariable comparison of the prevalence of autoimmune disease among those without any MGUS (whether clinical or screened, the control group), compared with different groups: individuals with a positive screening test for MGUS and those with a previous clinical diagnosis of MGUS, as well as both groups combined. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI), adjusting for age and sex, comparing the same two groups to the control group as in the univariable analysis. Results: Among 75,422 screened samples 3,358 had MGUS and 316 light chain MGUS (LC-MGUS). Of all screened individuals, 338 had a prior clinical diagnosis of MGUS or LC-MGUS and 234 had both clinical and screened MGUS, 104 were negative at screening. Individuals with MGUS were older (median age 70 vs 61, p<0.001) than those without MGUS and more frequently male (53.5% vs 45.3%, p<0.0001). Of all participants, 12,111 (16.1%) had a diagnosis of an autoimmune disease, whereof psoriasis, rheumatoid arthritis, polymyalgia rheumatica, ankylosing spondylitis, and diabetes mellitus type 1 were most common (Table 1). In the screened population, neither MGUS nor LC-MGUS were associated with autoimmune disease compared with individuals without MGUS or LC-MGUS (controls), OR 0.98 (95% CI 0.89-1.08) and 1.07 (95% CI 0.79-1.42), respectively. However, among individuals with a prior clinical diagnosis of MGUS, we found an association with autoimmune disease, OR 1.93 (95% CI 1.44- 2.56) (Figure 1). When the clinical and screened MGUS groups were combined the results were similar to the screened group alone (Figure 1). Conclusion: In this large, prospective, population-based screening of over 75,000 individuals, we did not find an association between MGUS or LC-MGUS and autoimmune disease. However, in sharp contrast, we did find a correlation with autoimmune disease among individuals diagnosed with MGUS in a clinical setting. Our results support the hypothesis that clinical case series and prior registry-based studies showing an increased risk of MGUS among patients with autoimmune diseases reflect a detection bias. This large, prospective screening study negates the previously reported biological correlation between autoimmune disease, MGUS and LC-MGUS and shows that autoimmune diseases are not associated with MGUS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

EPID-18. IATROGENIC IMMUNODEFICIENCY ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS OF THE CENTRAL NERVOUS SYSTEM: A TREATMENT PARADOX

Abstract BACKGROUND Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens. With increasing prevalence of autoimmune disease and development of new immunosuppressants, a genetically distinct entity known as iatrogenic immunodeficiency associated lymphoproliferative disorder (LPD) has emerged. Many of these cases arise following methotrexate use, challenging feasibility of standard HD-MTX regimens. The aim of this study was to further characterize this disorder and determine the optimal management strategy. METHODS We describe a case of a 76-year-old female with iatrogenic immunodeficiency associated PCNSL successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency associated LPD involving the CNS. We used a linear probability statistical model to determine correlations with outcome. RESULTS Natalizumab was associated with EBV negative tumors (p = 0.023), and EBV positive tumors were associated with improved outcomes (p = 0.016). Surgical resection was associated with improved outcomes (p = 0.032), although limited by potential confounding effect. Antiviral treatment (p = 0.095), rituximab (p = 0.111), and SCT (p = 0.198) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. CONCLUSION We propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency associated LPD of the CNS. Further study through prospective cohort studies or randomized clinical trials is warranted.

Alopecia areata: The disease of hairless patches on the scalp and any area of face

Up to 2% of the population is affected with alopecia areata (AA), a prevalent chronic tissue-specific autoimmune disease that causes hair loss. The specific pathobiology of AA is still unknown, however the most widely accepted idea is that an immunological process led the hair follicle's immune privilege to collapse. The etiology of AA is influenced by numerous environmental and genetic variables. One or more well-defined patches, more diffuse or total hair loss of the scalp (alopecia totalis), or hair loss of the entire body are all clinically treated for AA using a variety of clinical approaches (alopecia universalis). Corticosteroids and other immunomodulators, minoxidil, and contact immunotherapy are some of the available treatments for AA.

Iron: Not Just a Passive Bystander in AITD

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease all over the world and the most frequent cause of hypothyroidism in areas of iodine sufficiency. The pathogenesis of AITD is multifactorial and depends on complex interactions between genetic and environmental factors, with epigenetics being the crucial link. Iron deficiency (ID) can reduce the activities of thyroid peroxidase and 5'-deiodinase, inhibit binding of triiodothyronine to its nuclear receptor, and cause slower utilization of T3 from the serum pool. Moreover, ID can disturb the functioning of the immune system, increasing the risk of autoimmune disorders. ID can be responsible for residual symptoms that may persist in patients with AITD, even if their thyrometabolic status has been controlled. The human lifestyle in the 21st century is inevitably associated with exposure to chemical compounds, pathogens, and stress, which implies an increased risk of autoimmune disorders and thyroid dysfunction. To summarize, in our paper we discuss how iron deficiency can impair the functions of the immune system, cause epigenetic changes in human DNA, and potentiate tissue damage by chemicals acting as thyroid disruptors.

Prevalence of autoimmune diseases in patients with type 1 diabetes mellitus. DIACAM 1 study 2010–2020

ObjectiveTo evaluate the prevalence of autoimmune diseases (AD) associated with type 1 diabetes mellitus (T1DM). Patients and methodsAnalytical cross-sectional study, nested in a multicenter prospective cohort of 1121 ADults with DM1 with active follow-up in endocrinology clinics. Sociodemographic and clinical variables and the presence of AD were analysed in 2010 and 2020. ResultsIn this second analysis, 49,5% were male, mean age was 49.4±12.8 years, median T1DM duration was 27,1 years (20,7–35,1) and mean glycated hemoglobin was 7.66±1.06%. There is an absolute increase of 13% (95% CI 11–15) (P<.001) of patients with at least one AE and an absolute increase of 11.6% (95% CI 9.7–13.5) (P<.0001) of any type of autoimmune thyroid disease (ATD) after 10 years of follow-up. Likewise, the prevalence of celiac disease, autoimmune gastritis and other AD increased statistically significantly. In the multivariate logistic regression analysis, the factors that were independently associated with the presence of ATD were female gender [OR 2.9 (95% CI 2.3–3.7); P<.0001] and the presence of type 1b diabetes [OR 0.5 (95% CI 0.3–0.9); P=.041]. ConclusionsAfter 10 years of follow-up, there is a substantial increase in other types of AE in patients with DM1. It seems necessary to carry out a systematic screening of these AD to optimize the follow-up of patients with 1TDM, mainly of the ATD.

Multiple Sclerosis and Autoimmune Comorbidities

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by broad inter- and intraindividual heterogeneity and different prognoses. Multisystem comorbidities are frequent features in people with MS (PwMS) and can affect treatment choices, quality of life, disability and mortality. In this scenario, autoimmune comorbidities play a cardinal role for several reasons, such as the implication on MS pathogenesis, diagnostic delay, disease activity, disability progression, brain atrophy, and treatment choice. However, the impact of an autoimmune comorbid condition on MS is not fully elucidated. This review aims to summarize the currently available data on the incidence and prevalence of autoimmune diseases in PwMS, the possible effect of this association on clinical and neuroradiological MS course and its impact on treatment choice.

ODP273 Schmidt Syndrome Causing Multiorgan Failure

Abstract Introduction To our knowledge there has not been a case report published on the acute presentation of Schmidt syndrome (Polyglandular Autoimmune Syndrome Type 2) in which all three manifestations of type 1 diabetes mellitus (T1DM), primary adrenal insufficiency, and hypothyroidism were found and diagnosed at the same time. Case Description A 32-year-old male with suspected alcohol abuse presented to the hospital with nausea, vomiting, and weakness of two weeks duration after sustaining a fall. He was admitted for Diabetic Ketoacidosis (DKA) and shock requiring three pressors with unclear etiology. Labs were significant for severe hyponatremia of 113 mmol/L (136-145), elevated anion gap of 22, glucose 206 mg/dL (70-100), bicarbonate 11mmol/L (21-31), beta hydroxybutyrate 5.90 mmol/L (0. 0-0.42), and pH 7.22 (7.35-7.45) with Hemoglobin A1c 14.5% (&amp;lt;5.7). An insulin drip was instituted for DKA and the hyponatremia persisted. Cortisol was found to be suppressed at 3. 0 ug/dL (3.1-22.4) with significantly elevated ACTH 220.4 pg/mL (7.2-63.3) suggesting a new diagnosis of primary adrenal insufficiency. IV hydrocortisone 100 mg q8H was started on day 2 of hospitalization. Thyroid labs showed elevated TSH 10.10 uIU/mL (0.36-3.74) confirming hypothyroidism, prompting initiation of IV levothyroxine. His hospital course was complicated by cardiac arrest and acute respiratory failure requiring intubation. Cardiac work up was negative except for severe non-ischemic cardiomyopathy with significantly reduced ejection fraction of 20-25%. Bronchoscopy was performed and showed no evidence of obstructing pulmonary etiologies. SARS Coronavirus PCR was negative. He also had shock liver along with Disseminated intravascular coagulation (DIC). His kidney function worsened requiring continuous kidney replacement therapy (CRRT). Urine microscopy showed granular casts consistent with acute tubular necrosis. TPO antibodies, adrenal antibodies, GAD antibodies, and Zinc Transporter 8 antibodies all came back positive along with an undetectable C- peptide confirming the diagnosis of Hashimotos hypothyroidism, primary adrenal insufficiency, and T1DM respectively. He was eventually discharged on basal bolus insulin regimen, levothyroxine 75 mcg po daily, fludrocortisone 0. 05 mg po daily, and prednisone 5 mg po daily. The patient had multifactorial shock from an acute presentation of DKA, primary adrenal insufficiency, and hypothyroidism all presenting simultaneously. Conclusion This case illustrates the severe impact of having three endocrine organs affected all at once. The prevalence of Schmidt syndrome is very low at 1: 20,000 in the general population and can be associated with other non-endocrine autoimmune disorders. Prevalence of autoimmune thyroid disease is 70%, T1DM 50%, and Addison's disease is almost 100%. Due to the low prevalence, one needs a high clinical suspicion with the correct lab findings to diagnose this disease. Incorrect diagnoses or a late diagnosis can lead to life threatening consequences to the patient. The mainstay of treatment is hormone replacement, with corticosteroids given before thyroid replacement. Presentation: No date and time listed

The prevalence of thyroid dysfunction and autoimmune thyroid disease in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is one of the most common chronic non-organ-specific autoimmune diseases; meanwhile, autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease that can lead to hypo or hyperthyroidism. Although the etiology of both diseases is complex with a combination of genetic and environmental factors, there are overlaps in genes contributing to the pathogenesis of both diseases. Numerous studies found a correlation between thyroid abnormality and RA in different populations, yet some didn’t. This study is aimed to evaluate the prevalence of thyroid dysfunction, AITD, and anti-thyroid peroxidase (anti-TPO) positively in Iranian patients with RA.MethodsA total of 250 RA patients and 248 patients with non-inflammatory rheumatologic disease were included in this case–control study. All participants underwent complete clinical and laboratory assessments. Participants were also assessed for thyroid function testing, including anti-TPO antibodies.ResultsThyroid dysfunction was twice as common in RA patients as in controls (OR = 2.16; P-value > 0.001). Overt hypothyroidism was the most common thyroid dysfunction among RA patients (58 out of 84). Anti-TPO positivity was also significantly more common in RA compared with controls (OR = 2.65; P-value > 0.001). The proportion of controls and RA patients with AITD were 9 and 21.5%, respectively. AITD was found 2.8 times more common in RA group than controls (OR = 2.77; P-value > 0.001).ConclusionIt was demonstrated that RA was an independent factor associated with thyroid dysfunction and AITD.

Defining the Role of Monocytes in Sjögren's Syndrome.

Sjögren's syndrome is one of the most prevalent autoimmune diseases after rheumatoid arthritis, with a preference for middle age, and is characterised by exocrine glandular involvement leading to xerostomia and xerophthalmia. It can have systemic implications with vascular, neurological, renal, and pulmonary involvement, and in some cases, it may evolve to non-Hodgkin's lymphoma. For a long time, B- and T-lymphocytes have been the focus of research and have been considered key players in Sjögren's syndrome pathogenesis and evolution. With the development of new technologies, including omics, more insights have been found on the different signalling pathways that lead to inflammation and activation of the immune system. New evidence indicates that a third actor linking innate and adaptive immunity plays a leading role in the Sjögren's syndrome play: the monocyte. This review summarises the recent insights from transcriptomic, proteomic, and epigenetic studies that help us to understand more about the Sjögren's syndrome pathophysiology and redefine the involvement of monocytes in this disease.

Development of an enrichment-free one-pot sample preparation and ultra-high performance liquid chromatography-tandem mass spectrometry method to identify Immunoglobulin A1 hinge region O-glycoforms for Immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN) is a highly prevalent autoimmune renal disease. Human IgA1 with galactose deficiency in the hinge region (HR) has been identified as an autoantigen for this disease. Therefore, analyzing IgA1 HR glycoforms in biofluids is important for biomarker discovery. Herein, an analytical method that includes one-pot sample preparation with unbiased plasma IgA purification, dual internal standard addition, and sensitive ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectroscopy (UHPLC-QqQ-MS/MS) was developed. Targeted O-glycopeptides detection was performed in pooled plasma with the validation of theoretical retention times, enzymatic treatment outcomes, product ion scans, and signal repeatability. A total of 42 IgA1 O-glycopeptides with N-acetylgalactosamines, galactoses, and sialic acids were determined from 8 µL of plasma. The newly developed method was applied to plasma samples from 16 non-IgAN controls and 19 IgAN patients. Comparing the 42 targets, 16 IgA1 HR O-glycopeptides were statistically different between the two groups (p<0.05). Decreased sialylation was identified in the IgA1 hinge region of IgAN patients, which was also correlated with the estimated glomerular filtration rate (eGFR). The developed method is sensitive and precise and can be used to identify plasma biomarkers for IgA nephropathy.