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Background: CD20 + T cells represent up to 5% of circulating T lymphocytes. These cells have been shown to produce higher levels of IL-17A and IFN-γ than those of CD20 -  T lymphocytes. Some reports described the role of CD20 + T cells in autoimmune disorders such as multiple sclerosis and rheumatoid arthritis possibly due to their ability to produce these inflammatory cytokines. This study is aimed at describing the behavior of CD20 + T lymphocytes in the most frequent autoimmune disorder, i.e., Hashimoto's thyroiditis (HT), presenting isolated or associated to further autoaggressive disorders in a frame of poly-autoimmunity., Methods: The study group encompasses 65 HT patients: 23 presenting in isolated form (IT) and 42 with an associated non-endocrine autoimmune disorder [16 with chronic atrophic gastritis (CAG), 15 with nonsegmental vitiligo (VIT), and 11 with celiac disease (CD)]. Twenty healthy donors act as control group (HD). Chronic use of interfering drugs, severe or chronic disorders, and pregnancy and lactation were used as exclusion criteria. Whole blood samples (100 µl) were stained with fluorescent-labeled antibodies (anti-CD45, anti-CD3, anti-CD19, anti-CD16, anti-CD56, anti-CD4, anti-CD8, anti-CD20). Red blood cells were then lysed by adding 1 ml of hypotonic buffer, and samples were acquired on a Flow Cytometer., Results: CD3 + CD8 + CD20 + T lymphocytes' percentages, were significantly higher in the whole group of autoimmune patients compared to healthy donors (p = 0.0145). Dividing HT patients based on the type of presentation of autoimmune thyroiditis, CAG group showed the highest percentage of these cells as compared to HD and CD (p = 0.0058). IT patients showed higher percentages of CD3 + CD8 + CD20 + cells than those of HD patients although not reaching statistical significance. However, dividing IT group based on thyroid function, hypothyroid patients showed higher CD8 + CD20 + cell percentages than those of HD and euthyroid patients (p = 0.0111). Moreover, in IT patients, these cells were negatively correlated with FT4 levels (p = 0.0171; r = -0.4921)., Conclusions: These preliminary findings indicate that CD8 + CD20 + T cells are activated in patients with autoimmune thyroiditis and may behave differently according to the presence of poly-autoimmunity and hypothyroidism., (© 2024. The Author(s).)

Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine abnormalities. APS type 2 is the most common subtype of the syndrome, more often observed in adulthood, with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus type 1. Adrenal insufficiency is an essential and necessary clinical manifestation of the syndrome, as it is observed in 100 % of the cases, while it can be accompanied by hyperchloremic metabolic acidosis. Herein, we present a 23 years-old patient with adrenal insufficiency in the context of autoimmune polyglandular syndrome type 2 with coexisting autoimmune thyroiditis and metabolic acidosis with an increased anion gap attributed to prolonged malnutrition. Additionally, we analyze the main clinical features of adrenal insufficiency, which is a central component of autoimmune polyglandular syndrome; highlight characteristics that differentiate the major APS subtypes., Competing Interests: Declaration of competing interest There is no conflict of interest regarding this manuscript. All authors have read and have agreed with the final version., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated., (© 2024. The Author(s).)

Background: Interleukins (IL)-23, 31, and 33 are involved in the regulation of T helper 17 (Th17)/regulatory T (Treg) cells balance. The role of IL-23, 31 and 33 in non-endocrine autoimmune diseases has been confirmed. Data on the involvement of these cytokines in endocrine autoimmune diseases are limited., Objective: This study aimed to determine the involvement of cytokines regulating the T helper 17 (Th17)/regulatory T (Treg) cells axis in the course of autoimmune endocrine diseases., Methods: A total number of 80 participants were divided into 4 groups: the autoimmune polyendocrine syndrome (APS) group consisting of APS type 2 (APS-2) and type 3 (APS-3) subgroups, the Hashimoto's thyroiditis (HT) group, the Graves' disease (GD) group and the control (C) group. Fifteen cytokines related to Th17 and Treg lymphocytes were determined in the serum of all participants., Results: Higher levels of IL-23 and IL-31 were found in the APS, GD, and HT groups compared to the C group. Higher levels of IL-23 and IL-31 were also observed in the APS-2 group, in contrast to the APS-3 group. Correlation analysis of variables in the groups showed a statistically significant correlation between the cytokines IL-23, IL-31, and IL-33 in the APS and APS-2 groups, but no correlation in the APS-3 and C groups., Conclusion: IL-23 and IL-31 are independent factors in the course of HT, GD, and APS-2, in contrast to APS-3. The positive correlation between IL-23 and IL-31, IL-23 and IL-33, and between IL-31 and IL-33 in the APS, APS-2 groups, but the lack of correlation in the APS-3 and C groups may further suggest the involvement of these cytokines in the course of Addison's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED., Design: Cross-sectional cohort study combined with longitudinal follow-up data., Methods: We carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records., Results: The study subjects' median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found., Conclusions: Ovarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saari, Laakso, Tiitinen, Mäkitie and Holopainen.)

Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging to gut commensals was significantly increased in CVID serum (P < 0.0001), especially in patients with inflammatory manifestations (P = 0.0007). Levels of serum bacterial DNA were associated with parameters of systemic immune activation, increased serum IFN-γ, and the lowest numbers of isotype-switched memory B cells. Bacterial DNA was bioactive in vitro and induced robust host IFN-γ responses, especially among patients with CVID with inflammatory manifestations. Patients with X-linked agammaglobulinemia (Bruton tyrosine kinase [BTK] deficiency) also had increased circulating bacterial 16S rDNA but did not exhibit prominent immune activation, suggesting that BTK may be a host modifier, dampening immune responses to microbial translocation. These data reveal a mechanism for chronic immune activation in CVID and potential therapeutic strategies to modify the clinical outcomes of this disease.

Background: Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multiorgan autoimmune disease caused by the loss of central AIRE-controlled immune tolerance., Objectives: This study aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention., Methods: This study characterized the fecal microbiomes of 28 patients with APS-1 and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies, and tryptophan-related metabolites. Additionally, daily doses of the probiotic Lactobacillus rhamnosus GG were administered for 3 months., Results: Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with patients with APS-1 compared with healthy controls, with 6 mOTUs depleted and 8 enriched in patients with APS-1. Four overabundant mOTUs were significantly associated with severity of constipation. Phylogenetically conserved microbial associations with autoantibodies against cytokines were observed. After the 3-month intervention with the probiotic L rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L rhamnosus GG abundance was increased postintervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, 2 species positively associated with severity of diarrhea in patients with APS-1., Conclusions: The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a 3-month L rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria., (Copyright © 2021. Published by Elsevier Inc.)

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.

Context: The monogenic disorder autoimmune polyendocrine syndrome type 1 (APS-1) or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) manifests frequently with hypoparathyroidism, which requires treatment with oral supplementation with calcium and active vitamin D analogs. The majority of APS-1/APECED patients also suffer from intestinal malabsorption, which complicates the management of hypoparathyroidism and may lead to refractory severe hypocalcaemia. In such situations, reliance on intravenous calcium carries a high risk of nephrocalcinosis and renal damage., Methods: Here, we report our experience of periprocedural subcutaneous administration of recombinant human parathyroid hormone (rhPTH 1-34) in APS-1/APECED patients. Serum calcium was measured up to five times within the 36-hour period starting the evening before the scheduled procedure and ending the morning following the procedure., Results: Twenty-seven APS-1/APECED patients with hypoparathyroidism (aged 4-67 years) underwent 31 invasive gastrointestinal and/or pulmonary procedures. The patients received an average rhPTH1-34 dose of 9.6 ± 1.4 µg by subcutaneous injection. 92% of the adults and 54% of children in our cohort had evidence of nephrocalcinosis. Mean calcium levels remained stable and ranged from 2.06 to 2.17 mmol/L with minimal fluctuation. None of our patients experienced periprocedural adverse events connected with hypocalcaemia., Conclusion: rhPTH 1-34 is an alternative to conventional therapy in patients with APS-1/APECED and hypoparathyroidism undergoing invasive procedures. Subcutaneous PTH1-34 given directly before and after procedures resulted in well-controlled serum calcium levels maintained in the low-normal range and avoided the need for intravenous calcium which may contribute to renal calcifications and tubular damage., (© 2020 John Wiley & Sons Ltd.)

Context: The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed., Objective: To investigate CgA utility as a marker of endocrine autoimmunity., Methods: CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology., Results: Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P < 0.0001) and 3.89 (P = 0.0073) in patients with NET, T1D, AG, and AP, respectively. In AG, CgA and serum gastrin correlated positively (r = 0.55; P < 0.0001). The area under the receiver operating characteristic curve to predict AG was higher for parietal cell antibody (PCA) positivity than for CgA (0.84 vs 0.67; P < 0.0001). However, in combination with PCA and intrinsic factor autoantibodies, CgA independently improved prediction of AG (OR 6.5; P = 0.031). An impact of age on CgA positivity and on CgA value was detected (P < 0.0001) while current smoking significantly increased CgA serum levels by 25% (P = 0.0080)., Conclusion: CgA qualifies as a novel biomarker for T1D, AP, and AG., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Autoimmune polyglandular syndromes are combinations of various endocrine and nonendocrine autoimmune diseases, as well as the presence of elevated organ-specific antibody titers. We present a clinical case of a 41-year-old pregnant patient with type 2 autoimmune polyglandular syndrome, combining Addison's disease, Hashimoto's thyroiditis and hypogonadism. The pregnancy was achieved after the use of assisted reproductive technology. During the pregnancy the patient was strictly monitored. Glucocorticoid and mineralocor-ticoid replacement therapy was adjusted according to the electrolyte profile and general condition of the patient. Management during pregnancy was difficult due to fluctuations in electrolyte levels, thyroid hormones and orthostatic manifestations. Prior to delivery adrenal crisis occurred, but the condition was successfully managed. No complications were reported for the mother and the newborn., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The identification of autoantigens remains a critical challenge for understanding and treating autoimmune diseases. Autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic form of autoimmunity, presents as widespread autoimmunity with T and B cell responses to multiple organs. Importantly, autoantibody discovery in APS1 can illuminate fundamental disease pathogenesis, and many of the antigens found in APS1 extend to more common autoimmune diseases. Here, we performed proteome-wide programmable phage-display (PhIP-Seq) on sera from a cohort of people with APS1 and discovered multiple common antibody targets. These novel APS1 autoantigens exhibit tissue-restricted expression, including expression in enteroendocrine cells, pineal gland, and dental enamel. Using detailed clinical phenotyping, we find novel associations between autoantibodies and organ-restricted autoimmunity, including a link between anti-KHDC3L autoantibodies and premature ovarian insufficiency, and between anti-RFX6 autoantibodies and diarrheal-type intestinal dysfunction. Our study highlights the utility of PhIP-Seq for extensively interrogating antigenic repertoires in human autoimmunity and the importance of antigen discovery for improved understanding of disease mechanisms., Competing Interests: SV JD, MSA, and SEV have a provisional patent on clinical application of autoantigens described in this study. EF, DS, SS, BM, CM, ZQ, AC, MC, MG, ML No competing interests declared, JD JD is a scientific advisory board member of Allen and Company. JD, MSA, and SEV have a provisional patent on clinical application of autoantigens described in this study. MA MSA owns stock in Merck and Medtronic. JD, MSA, and SEV have a provisional patent on clinical application of autoantigens described in this study.

Objectives: The purpose of the present paper is to propose and introduce novel biomarkers of autoimmune polyendocrine syndromes that are relevant to the early diagnosis and optimal medical management of the patients who already suffer from type 1 diabetes mellitus., Methods: We hypothesize and demonstrate on a case study that various organ-specific autoimmune endocrinopathies can result in lowered basal insulin requirements, leading to unexplained hypoglycemia., Results: It can be hypothesized that hypothyroidism in patients with type 1 diabetes mellitus may deteriorate glycemic control and can lead to an increased rate of hypoglycemia, particularly the overnight and morning hypoglycemia. Thus, the decreased requirements for particularly overnight basal insulin can be an early marker of the autoimmune polyendocrine syndrome-3 with subclinical autoimmune thyroiditis in immune-mediated type 1 diabetes mellitus. Further, it could be proposed that unexplained hypoglycemia during the late afternoon or evening could be an early marker of the autoimmune polyendocrine syndrome-2 with subclinical autoimmune Addison disease in immune-mediated type 1 diabetes mellitus. As a result, an altered circadian pattern of basal insulin requirements can occur, characterized by a decreased late afternoon basal insulin rate., Conclusions: After exclusion of other causes, the unexplained reoccurring hypoglycemia can be a remarkable feature of autoimmune polyendocrine syndromes in immune-mediated type 1 diabetes mellitus on intensive insulin replacement therapy.

A 46-year-old woman was referred to the endocrinology clinic for evaluation of progressive fatigue, dizziness and treatment-resistant hypothyroidism. Initial laboratory results revealed hypothyroidism, hyponatraemia and hyperkalaemia. Liothyronine sodium (Cytomel) was initiated, which exacerbated her fatigue and dizziness. Suspecting adrenal insufficiency, an 08:00 cortisol level was obtained and found to be low with failure to increase following cosyntropin stimulation test. Diagnosis of primary adrenal insufficiency was confirmed via CT abdomen and pelvis revealing diminutive adrenal glands and elevated 21-hydroxylase antibody. Treatment was initiated with hydrocortisone 10 mg every morning and 5 mg at 16:00/day, with plan for patient follow-up in 3 weeks to assess need for mineralocorticoid replacement. Polyglandular syndromes are rare and have a wide variety of presentation. Thus, we recommend screening patients with a single autoimmune disorder who do not respond to conventional therapy to prevent possible life-threatening adrenal crisis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Autoimmune regulator (AIRE) mutations result in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome characterized by defective central T cell tolerance and the production of many autoantibodies targeting tissue-specific antigens and cytokines. By studying CD3- and AIRE-deficient patients, we found that lack of either T cells or AIRE function resulted in the peripheral accumulation of autoreactive mature naïve B cells. Proteomic arrays and Biacore affinity measurements revealed that unmutated antibodies expressed by these autoreactive naïve B cells recognized soluble molecules and cytokines including insulin, IL-17A, and IL-17F, which are AIRE-dependent thymic peripheral tissue antigens targeted by autoimmune responses in APECED. AIRE-deficient patients also displayed decreased frequencies of regulatory T cells (T regs ) that lacked common TCRβ clones found instead in their conventional T cell compartment, thereby suggesting holes in the T reg TCR repertoire of these patients. Hence, AIRE-mediated T cell/T reg selection normally prevents the expansion of autoreactive naïve B cells recognizing peripheral self-antigens., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The coexistence of adrenal failure with either autoimmune thyroid disease and/or type 1 diabetes is defined as autoimmune polyglandular syndrome (APS) type 2 or Schmidt's syndrome. Vitiligo, hypergonadotropic hypogonadism, chronic autoimmune hepatitis, alopecia, pernicious anaemia and seronegative arthritis may also be present. We present a case of 45-year-old Indian man with progressive jaundice and asthenia for 3 months. He was also found to have pallor, icterus, dry coarse skin and delayed relaxation of ankle jerk. Investigations showed pancytopaenia with megaloblastic changes due to pernicious anaemia, autoimmune hypothyroidism and autoimmune adrenalitis with evolving adrenal insufficiency. Upper gastrointestinal endoscopy guided biopsy showed evidence of gastric mucosal atrophy. Patient responded well to hydroxocobalamin and thyroxine replacement. Detailed workup to check for evolving APS II is prudent in a hypothyroid patient presenting with pallor and jaundice. It may alert physicians to possible adrenal crisis in the future, especially after starting levothyroxine replacement in these patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A 24-year-old man with no significant medical history presented to the medical clinic with vomiting and giddiness for 2 days, loss of appetite for 1 month and progressive fatigability for the preceding 4 months. On examination, he was found to be hypotensive and was admitted to the hospital for work-up. Considering his abnormal labs and physical findings, he was worked up and was diagnosed with primary adrenal insufficiency. On further work-up for the aetiology of his Addison's disease, he was found to have concurrent autoimmune thyroiditis and vitiligo. A final diagnosis of autoimmune polyglandular syndrome type 2 was made. The patient was started on hormone replacement therapy and reported improvement of symptoms on 3-month follow-up visit., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Backgraund and Objective: Anti-Saccharomyces Cerevisiae Antibodies (ASCA) that are considered to reflect immune response against increased intestinal permeability due to mucosal damage are among the serological markers of Crohn's Disease., Methods: This microbial seromarker was recently shown to be elevated in several autoimmune disorders such as celiac disease, autoimmune liver diseases, type 1 diabetes, and Graves' disease. Despite that fact, ASCA seropositivity in Autoimmune Polyglandular Syndrome (APS) has never been reported before., Results: Herein, we present a 46-year-old woman who has uveitis, autoimmune thyroiditis, and primary ovarian failure., Conclusion: Based on the coexistence of these diseases, the patient was diagnosed with APS type III. Moreover, ASCA seropositivity was detected although she has no overt intestinal disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We describe a very rare case of concurrent variant type 3 autoimmune polyglandular syndrome (APS) and pulmonary arterial hypertension (PAH). A previously healthy 65-year-old Japanese woman was referred to our university hospital with a 2-month history of general fatigue and hyperglycemia. Laboratory tests revealed severe hyperglycemia (plasma glucose 543 mg/dL and HbA1c 10.7%) with ketonuria (3+). Glutamic acid decarboxylase (GAD) and IA-2 antibodies were positive, and the serum C peptide level was markedly decreased to 0.2 ng/mL. Accordingly, type 1 diabetes was diagnosed. Hashimoto's thyroiditis was also diagnosed because she had a diffuse goiter and a mild hypothyroidism (TSH 8.20 μU/mL, and FT4 0.80 ng/mL) with positive autoantibodies for thyroid peroxidase and thyroglobulin. There was neither adrenal insufficiency nor hypocalcemia. In addition, chest X ray showed a suspicious PAH by a dilation of both pulmonary arteries, especially right descending artery, and right heart catheterization confirmed the presence of PAH. HLA Class II genotyping revealed DRB1-DQB1*0901-*0303, a common susceptibility haplotype in Japanese patients with type 3 APS or acute-onset type 1 diabetes. The combination of variant type 3 APS and PAH is extremely rare and to the best of knowledge, this is the first case reported in a Japanese patient.

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1., Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease., Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE., Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure., Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications., (Copyright © 2017 Endocrine Society)

Background: In recent years, scientific knowledge pertaining to the rare ORPHAN polyglandular autoimmune syndrome (registered code ORPHA 282196) has accumulated., Objective: To offer current demographic, clinical, serological and immunogenic data on PAS., Methods: Review of the pertinent and current literature., Results: Polyglandular autoimmune syndromes (PAS) are multifactorial diseases with at least two coexisting autoimmune-mediated endocrinopathies. PAS show a great heterogeneity of syndromes and manifest sequentially with a large time interval between the occurrence of the first and second glandular autoimmune disease. PAS cluster with several non-endocrine autoimmune diseases. In most endocrinopathies of PAS, the autoimmune process causes an irreversible loss of function, while chronic autoimmune aggressions can simultaneously modify physiological processes in the affected tissue and lead to altered organ function. The rare juvenile PAS type I is inherited in a monogenetic manner, whereas several susceptibility gene polymorphisms have been reported for the more prevalent adult types. Relevant for a timely diagnosis at an early stage is the screening for polyglandular autoimmunity in patients with monoglandular autoimmune disease and/or first degree relatives of patients with PAS. The most prevalent adult PAS type is the combination of type 1 diabetes with autoimmune thyroid disease., Conclusions: Early detection of specific autoantibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown PAS disease.

The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases - coeliac disease and autoimmune atrophic gastritis - they have radically changed gastroenterologists' diagnostic ability, while in others - autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis - their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Measurements of autoantibodies to interferon-ω (IFN-ω) in patients with autoimmune polyglandular syndrome type 1 (APS-1) were performed using a new immunoprecipitation assay (IPA) based on 125I-labeled IFN-ω., Methods: We have developed and validated a new IPA based on 125I-labeled IFN-ω. Sera from 78 patients (aged 3-78 years) with clinically diagnosed APS-1, 35 first degree relatives, 323 patients with other adrenal or non-adrenal autoimmune diseases and 84 healthy blood donors were used in the study. In addition, clinical features and autoimmune regulator (AIRE) genotype for the APS-1 patients were analyzed., Results: Sixty-six (84.6%) of 78 APS-1 patients were positive for IFN-ω Ab using 125I-labeled IFN-ω IPA. IFN-ω Ab was the most prevalent of the six different autoantibodies tested in this group of APS-1 patients. All 66 IFN-ω Ab-positive APS-1 patients had AIRE mutations and 7 IFN-ω Ab-negative patients had no detectable AIRE mutations, whereas 3 (3.8%) patients were discrepant for IFN-ω Ab positivity and AIRE mutation results. Out of autoimmune controls studied, two patients were positive for IFN-ω Ab. Positivity and levels of IFN-ω Ab in the APS-1 patients studied were similar irrespective of patient's clinical phenotype and AIRE genotype. Furthermore, IFN-ω Ab levels did not change over time (up to 36 years of disease duration) in 8 APS-1 patients studied., Conclusions: We have developed a novel, highly sensitive and specific assay for measurement of IFN-ω Ab. It provides a simple and convenient method for the assessment of patients with APS-1 and selecting patients suspected of having APS-1 for AIRE gene analysis.

Background: Acrodermatitis enteropathica (AE) is a rare dermatitis secondary to zinc deficiency most commonly seen as an inherited disease in infants. In the last decade, increased number of reports have been published on the acquired form that presents in adulthood. Unlike its inherited counterpart, acquired AE (AAE) is often secondary to underlying pathologic or iatrogenic etiologies that interfere with nutritional absorption, such as inflammatory bowel disease or alcoholism. Various gastrointestinal pathologies have been associated with AAE, but there is currently no report on its association with adult autoimmune enteropathy (AIE), a rare gastrointestinal disorder commonly seen in infants, with limited cases reported in adults. Here we present a case in which AAE was the initial clinical manifestation in an adult patient subsequently diagnosed with AIE., Case Presentation: A 41-year-old African American female presented to our emergency department at the Johns Hopkins Hospital with several months of progressively worsening dermatitis in the legs and acral regions, along with worsening symptoms of diarrhea, alopecia, poor oral intake, lethargy, hematochezia, peripheral edema, and weight loss. Our dermatology team was consulted given a presentation of exquisitely tender, erythematous, and diffusely desquamating skin lesions in the setting of two prior outside hospitalizations in the last 3 months with the same dermatitis that was refractory to topical and oral corticosteroids. Low serum zinc level and positive response to zinc supplementation confirmed the diagnosis of AAE. However, persistent hypovitaminosis and mineral deficiency despite aggressive nutritional supplementation prompted further investigation for an underlying malabsorption etiology. Jejunal biopsy and associated autoantibodies confirmed a diagnosis of adult AIE., Conclusion: This case highlights the fact that adult AIE can present initially with clinical findings of AE. While proper zinc supplementation can resolve the latter, recognizing this association can trigger earlier diagnosis, minimize unnecessary tests, and establish earlier intervention to improve quality of life and prevent recurrence of AAE. The case also highlights the importance of collaboration between general and subspecialist physicians in identifying a primary etiology to a secondary clinical presentation. This report can be beneficial to general internists and emergency physicians, as much as it can be to dermatologists, rheumatologists, and gastroenterologists.

A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol. While antibodies against pancreatic glutamic acid decarboxylase (GAD) were strongly positive (7,690 U/ml), fasting glucose level was 4.9 mmol/L and HbA1c was 6.3% on admission. As GAD antibody showed a high-titer of >10,000 U/ml and fasting plasma glucose level showed a rising trend, we performed 75-g oral glucose tolerance test (OGTT) 6 years after discharge. Whereas OGTT in 2012 showed impaired glucose tolerance, glucose tolerance had reverted to normal in 2014. A patient with a high-titer GAD antibody does not always have progressive glucose intolerance. GAD antibody positivity is common in not only type 1 diabetes, but also APS I and stiff-person syndrome (SPS). There are differences in recognized epitopes among the three disorders. Epitopes for GAD65 antibody associated with type 1 diabetes are located in the middle region and the COOH-terminal of the GAD65 protein, whereas epitopes associated with SPS reside in the NH2-terminal in addition to the middle region and COOH-terminal. The present case suggests that these differences in epitopes may be related to various pathogenic mechanisms including glucose intolerance.

Objectives: Autoimmune polyglandular syndrome type 3 - (APS-3), is defined as the coexistence of autoimmune thyroiditis with other non-ovarian autoimmune diseases without primary adrenal insufficiency. Additionally the definition of APS-3 also includes primary ovarian insufficiency (POI) coexistence with autoimmune thyroiditis. The main goal of that study is to assess the prevalence of APS-3 defined as coexistence of autoimmune thyroiditis with POI in population of 46 XX karyotype women with primary ovarian insufficiency (POI). The second goal is to investigate hormonal profile and insulin sensitivity in women with POI and subgroups of women with APS-3 - POI/APS-3(+) and without APS 3 - POI/APS-3(-)., Materials and Methods: Anthropometric measurements, coexistence of autoimmune diseases, androgens, fasting glucose and insulin, glucose and insulin at 60' and 120' of oral glucose tolerance test (OGTT) and homeostasis model for insulin resistance (HOMA-IR), were determine in 98 patients aged between 18 and 39 with spontaneous 46 XX primary ovarian insufficiency (POI), in 33 POI/APS-3(+), 65 POI/APS-3(-), and 75 healthy controls., Results: Continuous data were summarized by the mean±standard deviation (SD), and categorical data by number (percentages). Data were checked for normality using Shapiro-Wilk test, the comparison between groups were performed using non-parametric Mann-Whitney or Kruskall-Wallis test. Pearson's correlation coefficient was used to assess the relationships between parameters. Statistical significance was defined as p values <0.05. Autoimmune thyroid disease (ATD) was presented in 33/98 (33.7%) patients with POI. The groups did not differ significantly in respect to age and body mass index (BMI). Women with POI, POI/APS-3(+) and POI/APS-3(-) showed significantly lower serum androgens in comparison to controls. Additionally women with POI/APS-3(+) showed hyperinsulinemia after 1h of OGTT; No significant differences in serum fasting glucose, insulin and during 2h OGTT between groups were observed., Conclusions: The prevalence of APS-3 is 33.7% in patients with spontaneous 46 XX primary ovarian insufficiency. Women with POI, POI/APS-3(+) and POI/APS-3(-) feature lower testosterone, androstendione, dehydroepiandrostendione sulphate in comparison to controls. Women with POI/APS-3(+) could have hyperinsulinemia and should be carefully evaluated for metabolic disorders., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Normal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH)D]. A recent study presented deficiency of 25(OH)D levels in Swedish MG patients. We aimed to study 25(OH)D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH)D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age- and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH)D levels (mean 58.8 ± 16.3 and 62.0 ± 22.4 nmol/L, respectively) than PNP patients (mean 42.1 ± 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 ± 13.8 nmol/L, p = 0.01). Plasma 25(OH)D levels was lower with age in all groups. There were no correlations between 25(OH)D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH)D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls.

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection., (2015 BMJ Publishing Group Ltd.)

Purpose: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases., Methods: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months., Results: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%)., Conclusions: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Background: Although sarcoidosis and celiac disease are both chronic immunologic disorders involving multiple organ systems, reports about association of diseases in individual patients are sparse. While sarcoidosis is a chronic granulomatous disease presumably reflecting an exaggerated response to an unknown antigen, celiac disease is a T cell-driven disease triggered by ingestion of gluten, a protein composite found in wheat and related grains., Case Presentation: We present three cases with a longstanding history of sarcoidosis that have been additionally diagnosed with celiac-like enteropathy. In two cases, celiac disease was established applying celiac-specific serology and duodenal histology, while one case was revealed as an AIE-75-positive autoimmune enteropathy. The HLA-DR3/DQ2 haplotype was confirmed in both celiac patients, hence confirming previous data of linkage disequilibrium as a cause for disease association. Remarkably, one celiac patient presented with granulomatous nodulae in the ileum, thus reflecting an intestinal sarcoid manifestation. In contrast the patient with an autoimmune enteropathy, was HLA-DQ9/DQ6-positive, also arguing against CD., Conclusions: Associations of sarcoidosis and celiac disease are rare but do occur. Determining the HLA status in patients with complex autoimmune associations might help classifying involved disease entities.

Objective: Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown, which results in tissue-specific autoimmune diseases., Design: To evaluate the effect of a well-defined T-cell repertoire impairment on humoral self-reactive fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed using both one- and two-dimensional western blotting approaches against a broad spectrum of peripheral tissue antigens., Methods: Autoantibody patterns of APS 1 patients were compared with those of subjects affected by other autoimmune endocrinopathies (OAE) and healthy controls., Results: Using a Chi-square test, significant changes in the Ab repertoire were found when intergroup patterns were compared. A singular distortion of both serum self-IgG and self-IgM repertoires was noted in APS 1 patients. The molecular characterization of these antigenic targets was conducted using a proteomic approach. In this context, autoantibodies recognized more significantly either tissue-specific antigens, such as pancreatic amylase, pancreatic triacylglycerol lipase and pancreatic regenerating protein 1α, or widely distributed antigens, such as peroxiredoxin-2, heat shock cognate 71-kDa protein and aldose reductase. As expected, a well-defined self-reactive T-cell repertoire impairment, as described in APS 1 patients, affected the tissue-specific self-IgG repertoire. Interestingly, discriminant IgM reactivities targeting both tissue-specific and more widely expressed antigens were also specifically observed in APS 1 patients. Using recombinant targets, we observed that post translational modifications of these specific antigens impacted upon their recognition., Conclusions: The data suggest that T-cell-dependent but also T-cell-independent mechanisms are involved in the dynamic evolution of autoimmunity in APS 1.

Autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune regulator (AIRE) gene and is associated with neutralizing anti-cytokine autoantibodies. We have used an in vivo challenge model to analyze antigen-specific CD4(+) T cell responses. Bacille Calmette-Guérin (BCG)-vaccinated patients and controls were injected tuberculin intradermally, skin blisters were induced by suction on the indurations and on unexposed skin, and the infiltrating cells harvested. The patients had a quantitatively normal CD4(+) T cell response and no significant abnormalities in the expression of T helper type (Th) 1- or Th2-related genes. The expression of interleukin (IL)-22, in contrast, was lower in the patients. Two patients, both with a pre-existing ocular keratopathy, experienced a relapse of keratoconjunctivitis, suggesting a possible immunological basis for this APECED component. Our in vivo data are compatible with a selective IL-22 defect in the activated CD4(+) T cells of APECED patients, affecting also unexposed skin in steady-state conditions.

An important characteristic of autoimmune polyendocrine syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%. Type 1 IFN autoantibodies are detected by antiviral neutralizing assays (AVA), binding assays with radiolabelled antigens (RLBA), enzyme-linked immunosorbent assay (ELISA), or by reporter-based cell assays. We here present a simple and reliable version of the latter utilizing a commercially available cell line (HEK-Blue IFN-α/β). All 67 APS 1 patients were positive for IFN-ω nAbs, while 90% were positive for IFN-α2 nAbs, a 100% and 96% correlation with RLBA, respectively. All blood donors and non-APS 1 patients were negative. The dilution titer required to reduce the effect of IFN-ω nAbs correlated with the RLBA index. This cell-based autoantibody assay (CBAA) is easy to perform, suitable for high throughput, while providing high specificity and sensitivity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies and related to the muscle nicotinic acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK). Myasthenia gravis with anti-MuSK antibodies rarely occurs in children. The present article reports a childhood onset case of auto-immune MG with anti-MuSK antibodies, part of autoimmune polyglandular syndrome., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Diabetic lipemia, although common in type 2 diabetes, is rare in type 1 diabetes mellitus. It may manifest as lipemia retinalis, eruptive xanthomas, fatty liver, and pancreatitis. We describe a 6-year-old girl diagnosed with autoimmune poly-glandular syndrome type IIIa, who presented with diabetic lipemia manifesting as eruptive xanthomas. Probable metabolic derangements causing such severe lipid abnormalities and its treatment are discussed.

Context: Previous studies have identified the calcium-sensing receptor (CaSR) and NALP5 as parathyroid autoantibody targets in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). However, although NALP5 antibodies have been associated with the occurrence of hypoparathyroidism (HP) in APECED, it is unclear whether CaSR antibodies are a specific or sensitive marker for APECED-associated HP., Objective: The objective of the study was to identify associations between the presence of CaSR and NALP5 antibodies and the disease manifestations and demographic characteristics of Finnish APECED patients., Design, Subjects, and Methods: This was a case-control study including 44 APECED patients and 38 age- and sex-matched healthy controls. Antibodies against the CaSR and NALP5 were detected using immunoprecipitation assays and radioligand binding assays, respectively., Results: CaSR and NALP5 antibodies were detected in 16 of 44 (36%) and 13 of 44 (30%) patients, respectively. No statistically significant associations were found between the presence of CaSR or NALP5 antibodies and the disease manifestations of APECED including HP (P > .05). For the diagnosis of HP, CaSR and NALP5 antibodies had specificities of 83% and 50%, respectively, and sensitivities of 39% and 26%, respectively. A significant association between both a shorter APECED and HP duration (<10 y) and positivity for CaSR antibodies was noted (P = .019 and P = .0061, respectively)., Conclusion: Neither CaSR nor NALP5 antibodies were found to be specific or sensitive markers for HP in APECED. Further investigations are required to determine the exact role of the autoimmune response against the CaSR and NALP5 in the pathogenesis of this autoimmune syndrome.

Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor-binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor-binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell-activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α-driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.

Single-point-in-time ELISA optical densities for three putative antibodies identified in Sydenham's chorea, the streptococcal group A carbohydrate antigen, N-acetyl-beta-d-glucosamine, tubulin, and the dopamine 2 receptor, showed no differences in children with PANDAS (n=44) or Tourette syndrome (n=40) as compared to controls (n=24). Anti-tubulin and D2 receptor antibodies assessed in serial samples from 12 PANDAS subjects obtained prior to a documented exacerbation, during the exacerbation (with or without a temporally associated streptococcal infection), and following the exacerbation, showed no evidence of antibody levels correlating with a clinical exacerbation. These data do not support hypotheses suggesting an autoimmune hypothesis in either TS or PANDAS., (© 2013.)

In type 3 polyendocrine syndrome (PAS3), autoimmune thyroiditis occurs with other organ-specific autoimmune disease, but not with autoimmune adrenalitis. In this report we described a family from Pakistan in which mother and three daughters were affected by a PAS3. We studied a family from Pakistan: Father MMu age 44, mother KN aged 44, three daughters MM age 20, MH age 16 and MA age 14 and a son MU age 18. These subjects were tested for thyroids function, metabolic function, adrenal function, autoimmune disease. In this family the four females were shown hypothyroidism with presence of anti thyroid autoantibodies (AA) and high TSH serum concentration in association with the presence of anti transglutaminase AA. Moreover KN, MM and MH were positive for anti nuclear AA (granular pattern) and for antibodies against Saccaromyces cerevisiae. MM was positive for AA against nuclear extractable antigens (SSA and SSB) too. No diabetes or pernicious anemia were observed. Adrenal and Pituitary function were normal. PAS 3C is an uncommon disease. In this family from Pakistan we observed a PAS3C in the four female members: mother and three daughters while father and son were unaffected.

We present a 42-year-old woman with pre-existing autoimmune polyendocrinopathy syndrome (APS) Type 2 and chronic kidney disease due to Type 1 diabetic nephropathy, who developed a rapid deterioration in renal function due to perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated vasculitis. Although possibly a chance occurrence, ANCA have been detected more frequently in patients with a history of certain autoimmune diseases. Such an association may simply reflect an underlying tendency to immune system dysfunction in these patients and the finding of positive ANCA serology does not reliably herald the development of ANCA-associated vasculitis. However, our case illustrates that positive ANCA serology in such circumstances is not always a benign phenomenon and should still be interpreted within the clinical context. Moreover, clinicians managing patients with pre-existing autoimmune disease should maintain a low threshold for appropriate assessment should such patients develop evidence suggestive of vasculitis.

Patients with autoimmune polyendocrine syndrome type 1 (APS-1) frequently have autoantibodies directed against the aromatic amino acid hydroxylases tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH). We aimed to characterize these autoantibodies with regard to their antigenic determinants, their influence on enzymatic activity and their clinical associations. In particular, we wanted to compare autoantibodies against the two different isoforms of TPH, which display different tissue distribution. Using sera from 48 Scandinavian APS-1 patients we identified 36 patients (75%) with antibodies against one or more of these three enzymes. Antibodies against TPH1, but not TPH2, were associated with malabsorption in the whole Scandinavian cohort, while TH antibodies were associated with dental enamel hypoplasia in Norwegian patients. Subsequent experiments with selected patient sera indicated that while the C-terminal domain was the immunodominant part of TPH1, the epitopes of TPH2 and TH were mainly located in the N-terminal regulatory domains. We also identified a TPH1 specific epitope involved in antibody mediated inhibition of enzyme activity, a finding that provides new insight into the enzymatic mechanisms of the aromatic amino acid hydroxylases and knowledge about structural determinants of enzyme autoantigens. In conclusion, TPH1, TPH2 and TH all have unique antigenic properties in spite of their structural similarity., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Recovery of the ventricular function in a patient with cardiomyopathy is very rare. Autoimmune polyendocrine syndrome is also very rare. We herein report a case of reversed cardiomyopathy associated with autoimmune polyendocrine syndrome type II (Schmidt's syndrome) composed of Addison's disease, vitiligo and Hashimoto's thyroiditis. The ventricular function and size were reversed following the administration of suitable hormone replacement therapy for polyendocrine syndrome.