Additional Autoimmune Diseases Research Articles

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

General Characteristics of Our Patients Diagnosed with Autoimmune Hepatitis: Single Center Experience

Objective:Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by elevated liver enzymes and serum immunoglobulin levels, often accompanied by high titers of autoantibodies, typical histopathological findings, and a diagnosis established upon the exclusion of other liver diseases. The etiology of AIH is not fully understood. Our aim was to investigate the general characteristics of our AIH patients, the treatments administered, and the responses to these treatments, and to compare these with the data available in the literature. Materials and Methods:Between 2010-2020, data from 62 patients diagnosed with AIH at our clinic were retrospectively reviewed. The study investigated the general characteristics at the time of diagnosis, laboratory values, autoantibody levels, the presence of additional autoimmune diseases, liver histology, treatment status and responses, as well as average follow-up and survival times. Results:Of the patients, 57 (91.9%) were female, with a female to male ratio of 11:1, and the average age of all patients was 34.76±14.9 years. The average follow-up duration was 34.7±23.4 months, the average survival time was 105 months, and the 5-year survival rate was determined to be 92%. At the time of diagnosis, a more than tenfold increase in aminotransferase levels and acute hepatitis were statistically significantly higher in females (p

Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil

Background/objectivesThe primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC).MethodsThis cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism).ResultsThe prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml).ConclusionsIn conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC.

P238 Autoimmune comorbidities in microscopic colitis: retrospective analysis of consecutive single centre patients

Abstract Background Microscopic colitis (MC) is an autoimmune inflammatory condition that causes watery diarrhoea along with other symptoms like bowel incontinence, resulting in impaired quality of life and morbidity. MC is localized to the colon, although other autoimmune disorders are known to be more prevalent among MC patients. Methods A retrospective analysis of consecutive MC patients treated in Lithuanian University of Health Sciences Hospital Kauno Klinikos over the last 6 years was performed. Patient information was obtained from electronic records and reviewed for demographic characteristics and diagnosed conditions. Results 94 MC patients were treated in our centre since 2017, 46 (49 %) with collagenous colitis (CC), 39 (41.5 %) with lymphocytic colitis (LC), 2 (2.1 %) with incomplete CC and 7 (7.4 %) with incomplete LC. 77 patients were female (82 %). Median age was 59 years [44.8-70.3]. There was a tendency for men to be younger (median 42 [37-68]) than women (median 60 [50-70.5]) but not significantly (p>0.05). 31 MC patients (33 %) we diagnosed with concomitant autoimmune disorders. 20 patients (21.3 %) had autoimmune thyroiditis, 7 (7.4 %) had coeliac disease, 7 (7.4 %) had autoimmune skin conditions, 5 (5.3 %) had rheumatoid arthritis, 1 (1.1 %) had spondyloarthritis and 2 (2.1 %) had autoimmune hepatitis. 9 patients (9.6 %) had 2 autoimmune conditions in addition to MC and 1 patient (1.1 %) had 3. 16 (34.8 %) CC patients, 11 (28.2 %) LC patients and 4 (57 %) incomplete LC patients had autoimmune comorbidities. 3 (6.5 %) CC patients, 3 (7.7 %) LC patients and 1 (14.3) incomplete LC patient had coeliac disease. Autoimmune thyroiditis was observed in 11 (23.9 %) CC patients, 6 (15.4 %) LC patients and 3 (42.9 %) incomplete LC patients. 2 (4.3 %) CC patients and 3 (7.7 %) LC patients had rheumatoid arthritis. 5 (10.9 %) CC patients and 2 (5.1 %) LC patients has autoimmune skin disorders. The differences between CC and LC patients were not statistically significant. Both patients with autoimmune hepatitis had LC and the patient with spondyloarthritis had incomplete LC. Conclusion MC patients in our centre were frequently diagnosed with additional autoimmune disorders warranting vigilance in clinical practice. There was no difference between CC and LC patients. Incomplete LC patients had a higher proportion of autoimmune comorbidities and though the number of cases was low, this opens up prospects for future investigation.

THU242 An Adolescent Female With Autoimmune Hepatitis And Graves’ Disease: An Unusual Presentation And Challenges In Management

Abstract Disclosure: H.J. Velasquez: None. M.A. Ruiz Santillan: None. D.L. Paul: None. M. Tosur: None. Background: Presence of multiple autoimmune disorders in an individual is not uncommon. Simultaneous diagnoses of autoimmune hepatitis (AIH) and Graves’ disease in a previously healthy adolescent individual has not been previously reported. Here we report an unusual clinical presentation of both autoimmune conditions in an adolescent female. Case Presentation: A 13-year-old Hispanic female presented with jaundice, fatigue, and weight loss, was found to have hepatic failure. She tested positive for autoantibodies (Ab) associated with AIH (Kidney-Liver Microsome Ab >1:2560, n <1:20; IgG 3480 mg/dl, n 641-1353 mg/dl; Anti Smooth muscle Ab <1:20, n <1:20; ANA 1:1280, n <1:160). Family history was negative for autoimmune diseases. During admission she remained with tachycardia (heart rate >100 beats per minute) and elevated systolic blood pressure (>120 mm Hg). Family confirmed tachycardia and mild exophthalmos started recently before admission. Due to concern for additional autoimmune diseases, thyroid function tests were performed and resulted abnormal (TSH <0.010 uIU/ml, n 0.7-4.1 uIU/ml; Free T4 4.7 ng/dl, n 0.8-2.0 ng/dl; Free T3 1023 pg/dl, n 286-556 pg/dl; total T3 199 ng/dl, n 80-210). Further autoantibody tests were consistent with Graves’ disease (TSI Ab 7.67IU/L, n<=0.54), other thyroid antibodies were negative (Thyroid Peroxidase Ab < 3 IU/ml, n<= 5.6 IU/L and Anti-Thyroglobulin Ab < 3 IU/ml, n<= 4 IU/L). Due to liver failure, antithyroid medications were contraindicated. Pending liver biopsy to confirm AIH made steroids not an option due to risk of alteration in biopsy results. The patient was treated with propranolol alone. Once her thyroid hormone levels stabilized, she had liver biopsy and then was placed on a steroid regimen. Her hospitalization was complicated by decompensated cirrhosis with hyperammonemia (ammonia 180 umol/l, n 22-48 umol/l), hepatic encephalopathy and hemodynamically unstable requiring intubation and ICU transfer. Hyperammonemia responded well to rifaximin and lactulose. After clinical improvement, she was discharged home with high dose prednisone, propranolol, ursodiol, phytonadione, lactulose, rifaximin, and spironolactone. Total thyroidectomy was performed two months later for permanent treatment of Grave’s disease. She was evaluated for liver transplantation and approved for listing but given her clinical improvement, she was listed as inactive status. Conclusions: AIH and Graves’ disease can present simultaneously. Screening for thyroid disorders should be considered when AIH is suspected. Co-presence of AIH makes acute management of Graves’ disease particularly challenging. An individualized treatment approach should be implemented after carefully reviewing risk/benefit ratios of each treatment option. Presentation: Thursday, June 15, 2023

A new, all-encompassing aetiology of type 1 diabetes.

The aetiology of type 1 diabetes (T1D) is considered multifactorial with the contribution of the MHC on chromosome 6 being most important. Multiple factors also contribute to the aetiology of colorectal neoplasia, but the final event causing the change from normal mucosa to polyp and from polyp to cancer is due to a single somatic mutation event. Repeated formation of colorectal neoplasia within an at-risk population results in a predictable, tapering, exponential neoplasia distribution. Critical mutations driving colorectal neoplasia formation occur in mutation-prone DNA. These observations led to three hypotheses related to T1D. First, a single somatic mutation within the MHC of antigen presenting cells results in a change in phenotype from normal to T1D. Second, the distribution of additional autoimmune diseases (AAIDs) among persons with T1D adheres to a predictable, tapering, exponential distribution. And third, critical mutations driving development of T1D occur in mutation-prone DNA. To address the hypotheses in an orderly fashion, a new analytical method called genome-wide aetiology analysis (GWEA) consisting of nine steps is presented. All data required for GWEA of T1D are obtained from peer-reviewed publications or publicly available genome and proteome databases. Critical GWEA steps include AAID distribution among persons with T1D, analysis of at-risk HLA loci for mutation-prone DNA, determination of the role of non-MHC genes on GWAS, and verification of human data by cell culture or animal experiments. GWEA results show that distribution of AAID among persons with T1D adheres to a predictable, tapering, exponential distribution. A single, critical, somatic mutation within the epitope-binding groove of at-risk HLA loci alters HLA-insulin-peptide-T-cell-receptor (TCR) complex binding affinity and creates a new pathway that leads to loss of self-tolerance. The at-risk HLA loci, in particular binding pockets P1, P4 and P9, are encoded by mutation-prone DNA: GC-rich DNA sequence and somatic hypermutation hotspots. All other genes on GWAS can but do not have to amplify the new autoimmune pathway by facilitating DNA mutations, changing peptide binding affinity, reducing signal inhibition or augmenting signal intensity. Animal experiments agree with human studies. In conclusion, T1D is caused by a somatic mutation within the epitope-binding groove of an at-risk HLA gene that affects HLA-insulin-peptide-TCR complex binding affinity and initiates an autoimmune pathway. The nature of the peptide that binds to a mutated epitope-binding groove of an at-risk HLA gene determines the type of autoimmune disease that develops, that is, one at-risk HLA locus, multiple autoimmune diseases. Thus, T1D and AAIDs, and therefore common autoimmune diseases, share a similar somatic mutation-based aetiology.

Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID).

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation. In this study, we evaluated the serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD). Our results showed increased serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-α, IL-1β, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD. These findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects.

A population-based study on autoimmune disease

The increasing prevalence of autoimmune diseases has become one of the leading concerns in public health. 1 Wang L Wang FS Gershwin ME Human autoimmune diseases: a comprehensive update. J Intern Med. 2015; 278: 369-395 Crossref PubMed Scopus (505) Google Scholar , 2 Greiner W Patel K Crossman-Barnes CJ Rye-Andersen TV Hvid C Vandebrouck T High-expenditure disease in the EU-28: does drug spend correspond to clinical and economic burden in oncology, autoimmune disease and diabetes?. PharmacoEconom Open. 2021; 5: 385-396 Crossref PubMed Scopus (8) Google Scholar Autoimmune diseases occur when the immune system mistakenly attacks healthy cells and tissues in the body, leading to chronic inflammation, tissue damage, and organ dysfunction. 1 Wang L Wang FS Gershwin ME Human autoimmune diseases: a comprehensive update. J Intern Med. 2015; 278: 369-395 Crossref PubMed Scopus (505) Google Scholar As more people are diagnosed with autoimmune disease, the burden on health-care systems, families, and communities grows. 2 Greiner W Patel K Crossman-Barnes CJ Rye-Andersen TV Hvid C Vandebrouck T High-expenditure disease in the EU-28: does drug spend correspond to clinical and economic burden in oncology, autoimmune disease and diabetes?. PharmacoEconom Open. 2021; 5: 385-396 Crossref PubMed Scopus (8) Google Scholar Adequate public health and service delivery planning requires reliable information about contemporary population-level disease incidence; however, there is a poor understanding about the estimates of autoimmune diseases and their temporal trends in many countries. 3 Scherlinger M Mertz P Sagez F et al. Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014. Autoimmun Rev. 2020; 19102531 Crossref PubMed Scopus (53) Google Scholar Little is known about the similarities and differences between these diseases concerning the incidence, prevalence, and co-occurrence. 4 Głowińska-Olszewska B Szabłowski M Panas P et al. Increasing co-occurrence of additional autoimmune disorders at diabetes type 1 onset among children and adolescents diagnosed in years 2010-2018-single-center study. Front Endocrinol (Lausanne). 2020; 11: 476 Crossref PubMed Scopus (9) Google Scholar Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UKAutoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Full-Text PDF

Characteristics of adult-onset auto-immune type 1 diabetes

BackgroundClassically described as a disease of childhood and adolescence, diabetes mellitus type 1 (T1DM) can occur in adulthood. Adult-onset T1DM is poorly documented and is often misdiagnosed. This study aims to describe the epidemiological aspect of T1DM with adult-onset and detail its clinical, paraclinical, and therapeutic characteristics. Materials and methodsA 9-year retrospective longitudinal study (2011-2019) was conducted including adult patients (age >20 years) with confirmed diabetes and at least one of the auto-antibodies (auto-Abs) to glutamic-acid-decarboxylase (GAD), to islet-tyrosine-phosphatase 2 (IA2) or islet-cell-antibodies (ICA) positive. ResultsA total of 166 patients were included (sex-ratio M/F: 1.34; mean age: 28.6 years [20-56 years]). At the onset, 50.6% of patients presented with diabetic ketosis and 13.3% with diabetic ketoacidosis. Cardinal symptoms of diabetes were present in 30.7% of patients only at diagnosis, while the discovery was fortuitous in 5.4% of cases. 27.7% of patients developed an additional auto-immune disease mainly autoimmune thyroid disease. The risk of developing another AUTO-IMMUNE DISEASE was highest in females (p = 0.010) and increased with age (p = 0.011). GAD-Abs, IA2-Abs, and ICA were positive in 98.2%, 13.3%, and 17.4% of cases respectively. Only GAD-Abs were found positive in 73.1%. Upon diagnosis, 75.9% of patients were treated with insulin, while 24.1% of patients were initially put on oral anti-diabetic drugs before requiring insulin within an average of 7.42 months. ConclusionsAdult-onset T1DM has a different clinical course (slower onset, less abrupt symptoms, more insidious presentation, and more prolonged progression to insulin) that has to be known. Misdiagnosis of adult-onset T1DM can have serious consequences.

Contrasting Autoimmune Comorbidities in Microscopic Colitis and Inflammatory Bowel Diseases.

Inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and microscopic colitis (lymphocytic and collagenous colitis) are immune-mediated diseases of the gastrointestinal tract, with distinct pathophysiology. We sought to compare the prevalence of autoimmune diseases between microscopic colitis (MC) and inflammatory bowel diseases (IBDs) in our patient cohorts in their medical history. We collected data from 611 patients (508 with IBD, 103 with MC). We recorded cases of other autoimmune diseases. The screened documentation was written in the period between 2008 and 2022. We sought to determine whether colonic involvement had an impact on the prevalence of autoimmune diseases. Ulcerative colitis patients and patients with colonic-predominant Crohn's disease had a greater propensity for autoimmune conditions across the disease course than patients with ileal-predominant Crohn's disease. Gluten-related disorders were more common in Crohn's disease than in ulcerative colitis, and slightly more common than in microscopic colitis. In ulcerative colitis, 10 patients had non-differentiated collagenosis registered, which can later develop into a definite autoimmune disease. Predominantly colonic involvement can be a predisposing factor for developing additional autoimmune disorders in IBD. Ulcerative colitis patients may have laboratory markers of autoimmunity, without fulfilling the diagnostic criteria for definitive autoimmune disorders (non-differentiated collagenosis).

Altered RNA Editing in Atopic Dermatitis Highlights the Role of Double-Stranded RNA for Immune Surveillance

Atopic dermatitis (AD) is associated with dysregulated type 1 IFN‒mediated responses, in parallel with the dominant type 2 inflammation. However, the pathophysiology of this dysregulation is largely unknown. Adenosine-to-inosine RNA editing plays a critical role in immune regulation by preventing double-stranded RNA recognition by MDA5 and IFN activation. We studied global adenosine-to-inosine editing in AD to elucidate the role played by altered editing in the pathophysiology of this disease. Analysis of three RNA-sequencing datasets of AD skin samples revealed reduced levels of adenosine-to-inosine RNA editing in AD. This reduction was seen globally throughout Alu repeats as well as in coding genes and in specific pre-mRNA loci expected to create long double-stranded RNA, the main substrate of MDA5 leading to type I IFN activation. Consistently, IFN signature genes were upregulated. In contrast, global editing was not altered in systemic lupus erythematosus and systemic sclerosis, despite IFN activation. Our results indicate that altered editing leading to impairment of the innate immune response may be involved in the pathogenesis of AD. Possibly, it may be relevant for additional autoimmune and inflammatory diseases.

Comorbid autoimmune diseases and burden of diabetes-related complications in patients with type 1 diabetes from a Mediterranean area

AimTo assess the prevalence of autoimmune diseases (AID) in patients with type 1 diabetes (T1D) and to evaluate whether the rate of diabetes-related complications differs depending on the presence of AID. MethodsCross-sectional analysis of 13,570 T1D patients aged ≥ 18 years registered in the SIDIAP database. The association between AID and diabetes-related complications was assessed by multivariable logistic regression models. ResultsThe prevalence of AID was 18.3% with thyroid AID being the most common. Patients with T1D and AID were more often female and their current age, age of diabetes onset and diabetes duration were higher. Patients with only thyroid AID experienced a lower risk of peripheral artery disease (odds ratio [OR] = 0.51, 95%; confidence interval [CI] 0.31 to 0.81) and kidney disease (OR = 0.68, 95%; 95% CI 0.54 to 0.85), whereas patients with other AID had an increased risk of ischemic heart disease (OR = 1.48, 95%; 95% CI 1.04 to 2.06). ConclusionsThe burden of diabetes-related complications in patients with T1D differs according to the type of additional AID. The presence of diabetes complications is lower in those with autoimmune thyroid disease while the presence of other AID is associated with higher rates of ischemic heart disease.

Multi-trait and cross-population genome-wide association studies across autoimmune and allergic diseases identify shared and distinct genetic component

ObjectivesAutoimmune and allergic diseases are outcomes of the dysregulation of the immune system. Our study aimed to elucidate differences or shared components in genetic backgrounds between autoimmune and allergic diseases.MethodsWe...

Autoimmune diseases accompanying Hashimoto thyroiditis in pediatric patients

AIM: Hashimoto thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents living in iodine-sufficient regions. In this study, we aimed to investigate the coexistence of other accompanying autoimmune diseases in patients aged 5–18 years who were diagnosed and followed up at the Pediatric Endocrinology Clinic of our hospital.MATERIAL AND METHODS: A total of 220 patients aged 5–18 years who were diagnosed with HT at the Pediatric Endocrinology Clinic of the University of Health Sciences Ankara City Hospital. Patient’ age at admission, sex, family history, complaints at admission, comorbidities, physical examination and laboratory findings, and clinical follow-up information were retrospectively reviewed.RESULTS: Of the 220 patients, 77.7% were female and 22.2% were male, with a mean age of 13.8±3.3 years. Of the 51.4 had euthyroidism, 40.4% had subclinical hypothyroidism,and 8.2% had overt hypothyroidism, respectively. Anti-thyroid peroxidase antibody was detected in 97% of patients and anti-thyroglobulin antibody (anti-Tg) was detected in 74% of patients. There was a family history of autoimmune disease in 36.4% of the patients. Autoimmune disease were present in 45 patients (20.4%). The most common autoimmune diseases in the patients were type 1 diabetes mellitus (T1DM) (14%), celiac disease (5%), skin diseases (2.7%), and rheumatologic diseases (1.3%). No statistically significant differences were found between the sex, age at diagnosis, current age, family history of autoimmune disease and thyroid function status of patients with HT and T1DM.The mean age of the patients followed up with HT with and without additional autoimmune disease was similar (p=0.644). In both groups, female sex was dominant. However, the number of male patients (35.6%) in the group with additional autoimmune disease was statistically significantly elevated than the group without autoimmune disease (19.9%) (p=0.016). The rate of subclinical hypothyroidism was statistically significantly elevated in the group without additional autoimmune disease (p<0.001). A statistically significant relationship was found between elevated Anti-Tg and additional autoimmune disease (OR=2.32 (95% CI; 1.16–4.56). The prevalence of additional autoimmune disease was increased 2.32 times in patients with elevated anti-Tg levels.There was no statistically significant correlation between the sex of the patients, their thyroid function status and thyroid autoantibodies (p=0.507). However, the prevalence of celiac disease was statistically significantly elevated in female patients (43.5%) than in male patients (6.7%) (p=0.014). In addition, the prevalence of T1DM was found to be statistically significantly elevated in males (93.8%) compared to females (52.2%) (p=0.007). 13.3% of patients with additional autoimmune disease were under the age of 10 and 64.4% were above the age of 10, this was statistically significant (p<0.01). T1DM was the most common autoimmune disease in both groups.CONCLUSION: As shown in our study, autoimmune diseases, especially T1DM and celiac disease, are associated with HT. It should be kept in mind that there is an increased risk of autoimmune disease in HT that affects both sexes and increases with age. In particular, regular follow-up of HT patients with elevated anti-Tg levels in terms of autoimmune disease development is important in terms of earlier diagnosis of diseases and reducing their morbidity.

Epidemiology, Survival, and Clinical Characteristics of Inclusion Body Myositis.

ObjectiveWe performed a population‐based study on inclusion body myositis with the primary aims to define the prevalence, survival rate, and incidence, and to investigate the symptom profiles associated with disease duration and sex over a 33‐year period.MethodsPatients diagnosed between 1985 and 2017 in Region Västra Götaland, Sweden, were identified according to the European Neuromuscular Centre diagnostic criteria from 2011.ResultsWe identified 128 patients, 89 men and 39 women, with the strict clinicopathological definition of inclusion body myositis. The prevalence was 32 per million inhabitants, 19 per million women and 45 per million men, by December 31, 2017. Mean incidence was 2.5 per million inhabitants and year. Mean age at symptom onset was 64.4 years with quadriceps weakness being the most common presenting symptom followed by finger flexor weakness. Dysphagia was a common presenting symptom being more frequent in women (23%) than men (10%) and was during the disease course reported in 74% of men and 84% of women. Seventy‐three patients were deceased, with a mean survival of 14 years from symptom onset. Survival rates from both diagnosis date and symptom onset were decreased compared to the matched population.Twenty‐one percent of the patients had an additional autoimmune disease. A cross‐sectional analysis of autoantibodies in 50 patients and 28 matched controls showed autoantibodies to cytosolic 5′‐nucleotidase 1A in 40% of the patients and 3.6% of controls.InterpretationInclusion body myositis is an autoimmune disease with decreased survival rate and with marked sex differences in both prevalence and clinical manifestations. ANN NEUROL 2022;92:201–212

Additional autoimmune diseases associated with type 1 diabetes in children and adolescents: A French single-center study from 2014 to 2021

ContextPatients with type 1 diabetes (T1D) are more likely to develop other autoimmune diseases than the general population. ObjectivesTo describe additional autoimmunity in a cohort of children and adolescents with T1D, as well as to identify factors associated with the presence of additional autoantibodies (AABs) and of additional autoimmune diseases (AADs). SettingThis was a single-center retrospective cohort study of 179 children and adolescents (median age: 9.1 years) diagnosed with T1D between 2014 and 2020 in a specialized center in France. Patients were screened for autoimmune thyroiditis and celiac disease at T1D diagnosis and once every 1–2 years during follow-up. Other AADs and their specific autoantibodies were screened for only if clinical or laboratory signs were present. ResultsAt T1D diagnosis, 15.6% of participants presented with at least one type of AAB including antibodies specific to Hashimoto's disease (TPOAb and/or TGAb) and/or to celiac disease (tTGAb and/or EMAb). Only 2.8% of participants presented with an AAD as early as T1D diagnosis. The median follow-up was 37 months. The cumulative incidence of AABs and AADs at 2 years of follow-up was, respectively, 3.9% and 5.4%, and it doubled at 3 years of follow-up. Only one patient, also affected by Down syndrome, was diagnosed with 2 AADs. Hashimoto's disease was the most frequently diagnosed AAD, followed by celiac disease, both at an asymptomatic stage. Vitiligo and Graves’ disease were also diagnosed in this cohort but affected few patients. Children aged 6–12 years were more likely to present with an AAD at diabetes diagnosis (p = 0.043). Conclusion: The high prevalence and incidence of additional autoimmunity in children and adolescents with T1D justifies regular screening of AABs and AADs.

High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease.

We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD+ children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD- children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time.

Hashimoto Thyroiditis, Anti-Parietal Cell Antibodies: Associations With Autoimmune Diseases and Malignancies.

BackgroundHashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT patients: a) the prevalence of APCA in an attempt to define their clinical phenotype and b) any possible associations of APCA with other autoimmune diseases and malignancies.MethodsThis is a single-center, case-control study, conducted at a University Hospital. The study included patients with HT diagnosed between November 2017 and November 2020. Excluded were patients <18 years old, with sonographic features of HT but negative thyroid peroxidase (TPOAbs) or thyroglobulin autoantibodies (TgAbs), Graves’ disease, Down or Turner’s syndrome.ResultsA total of 840 patients with HT were included in the study, from whom 180 (21.4%) had positive APCA. A total of 79 patients (9.4%) had one or more organ-specific autoimmune diseases and 61 (7.3%) had a systemic autoimmune disease. Autoimmune diseases were more frequent in female than in male patients (17.9% versus 10.9%, p = 0.05). APCA-positive patients were older than APCA-negative (54.1 ± 13.5 versus 49.0 ± 14.6, p <0.001) and had more often positive TPOAbs (93.3% versus 83.9%, p=0.001). Gastric neoplasms were documented only in APCA-positive patients (p <0.001). A higher frequency of organ-specific autoimmune diseases was observed in the APCA-positive group (14.4% versus 8%, p = 0.024). In the subgroup of patients with additional autoimmune diseases (n = 140), younger age and positive APCA were independently associated with the presence of organ-specific autoimmunity (OR 0.954, 95% CI 0.927–0.982 and OR 3.100, 95% CI 1.256–7.652, respectively). Papillary thyroid cancer (PTC) occurred in 3.5% of patients (26/29 women). Positive family history for thyroid autoimmunity and negative TPOAbs were the only independent risk factors for PTC among women (OR 3.228, 95% CI 1.173–8.887 and 0.315, 95% 0.113–0.881, respectively).ConclusionThis study reveals for the first time an association of APCA with organ-specific autoimmunity in HT patients. APCA together with patient age were independently associated with the presence of organ-specific autoimmunity. Finally, this study showed an association between APCA and gastric neoplasms in these patients.

Deficiencia de IgA y comorbilidades autoinmunes en la artritis idiopática juvenil

Objectives(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentre cohort of patients with juvenile idiopathic arthritis (JIA), and (2) to assess whether patients with JIA and IgAD have additional autoimmune disorders more frequently than patients with JIA and normal serum levels of IgA. MethodsRetrospective chart review of a cohort of patients with JIA managed in the paediatric rheumatology units of 2hospitals in Madrid, Spain. ResultsThis study included 193 patients, 123 (64%) female. The median age at disease onset was 5.6 years (IQR 2.5–9.7) and the median duration of followup was 5.1 years (IQR 2.2–8.1). The 3most common categories of JIA based on the ILAR classification were oligoarticular (53%), poliartritis RF-negative (20%) and enthesitis-related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All patients underwent periodic ophthalmic examinations. Eighteen children (9%) had anterior uveitis, which was chronic in 15 and acute in 3. Serum levels of anti-transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); 2of them had IgAD (OR=6.4; 95% CI, 0.9–47.6; p=.12). Only 1 of these 153 patients (0.7%) had hyperthyrotropinaemia with positive anti-thyroid antibodies and required replacement therapy. ConclusionPatients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.

Familial autoimmunity in pediatric patients with type 1 diabetes (T1D) and its associations with the severity of clinical presentation at diabetes diagnosis and with coexisting autoimmunity.

PurposeThe aim was to evaluate the impact of familial autoimmunity on the age and severity of type 1 diabetes (T1D) presentation and on the coexistence of other autoimmune diseases.MethodsWe retrospectively evaluated the medical records of 121 children/adolescents (male: 63) followed in our Diabetic Clinic from 2002 to 2016.ResultsSeventy-six patients (62.8%) had at least one relative with an autoimmune disease, Hashimoto’s thyroiditis (49.5%) and T1D (22.3%) being the commonest. Children with familial autoimmunity were younger at T1D diagnosis (mean age ± SD) (6.766 ± 3.75). Median fasting c-peptide levels at presentation were not related to familial autoimmunity. Patients with familial autoimmunity more often exhibited GADA autoantibody positivity at diagnosis. The larger the number of the patient’s relatives diagnosed with an autoimmune disease, the higher were the patient’s GADA levels (Spearman’s rho test = 0.19, p = 0.049). Children with a first-degree relative with autoimmunity had a coexisting autoimmune disorder at a significantly higher percentage (p = 0.016). Family history of autoimmunity was negatively associated with the presence of diabetic ketoacidosis (DKA) (p = 0.024). Patients with a relative with T1D less frequently exhibited DKA at diagnosis (12.8 vs. 87.2%, p = 0.003). The presence of DKA was associated with younger age (p = 0.05) and lower c-peptide levels (p = 0.033).ConclusionsFamilial autoimmunity was present in 62.8% of children with T1D, autoimmune thyroiditis and T1D being the two most frequent familial autoimmune diseases. Familial autoimmunity reduced the risk of DKA at diagnosis, but these patients were younger and had higher levels of pancreatic autoantibodies and a greater risk of developing additional autoimmune diseases.