effect on granulosa cells, luteal cells and oocyte maturation (8) . Euthyroid women with thyroid autoimmunity are twice as likely to experience spontaneous miscarriages (9) . This probably represents a generalised activation of the immune system, or an
Kusum Lata, Pinaki Dutta, Subbiah Sridhar, Minakshi Rohilla, Anand Srinivasan, G R V Prashad, Viral N Shah and Anil Bhansali
Aaron Lerner, Patricia Jeremias and Torsten Matthias
mucosa and luminal ecosystems involvement in the thyroid autoimmunity: (i) Gut dysbiosis might disturb the finely tuned immune balance and break tolerance to self-antigens and non-pathogenic non-self-antigens, by posttranslational modification proteins
Nancy J Olsen, Ann L Benko and William J Kovacs
modulate autoimmunity. An association of Klinefelter's syndrome with lupus has been reported in several studies, and in isolated case reports, reversal of hypogonadism in such patients with Klinefelter's syndrome by testosterone replacement has been
Stavroula A Paschou, Nektaria Papadopoulou-Marketou, George P Chrousos and Christina Kanaka-Gantenbein
pancreas. A small percentage of affected patients (<10%) are classified as type 1B, with no evidence of autoimmunity and the pathogenesis in these cases is considered idiopathic ( 1 , 2 ). The aim of this comprehensive review is to present updated
The origin of autoimmune disease type 1 diabetes is still unknown.
This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers.
Materials and methods
The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers.
Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects.
These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients.
These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.
Xiangyu Gao, Wanwan Sun, Yi Wang, Yawen Zhang, Rumei Li, Jinya Huang and Yehong Yang
). Historically, based on positivity of islet autoantibodies, diabetes mellitus had been classified into two clinical types: type 1 diabetes (T1DM) and type 2 diabetes (T2DM) ( 3 , 4 ). The progressive destruction of islet β cell mass caused by islet autoimmunity
Lauren Bell, Ann Louise Hunter, Angelos Kyriacou, Annice Mukherjee and Akheel A Syed
compared to TRAb measurement in a UK university teaching hospital. Whereas previous observational studies involving thyroid autoimmunity in clinical practice have evaluated the sensitivity and specificity of TRAb tests against the premise of definitiveness
Emmi Naskali, Katja Dettmer, Peter J Oefner, Pedro A B Pereira, Kai Krohn, Petri Auvinen, Annamari Ranki and Nicolas Kluger
ja Addison Ry, http://www.apeced.org) . Most of these patients have been included in various publications on APECED in Finland ( 1 , 13 ), including our previous work about gastrointestinal autoimmunity ( 9 ). The mean age of the cohort was 39
Ghazala Zaidi, Vijayalakshmi Bhatia, Saroj K Sahoo, Aditya Narayan Sarangi, Niharika Bharti, Li Zhang, Liping Yu, Daniel Eriksson, Sophie Bensing, Olle Kämpe, Nisha Bharani, Surendra Kumar Yachha, Anil Bhansali, Alok Sachan, Vandana Jain, Nalini Shah, Rakesh Aggarwal, Amita Aggarwal, Muthuswamy Srinivasan, Sarita Agarwal and Eesh Bhatia
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.
Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.
Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.
Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.
Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.
Chiara Mele, Maria Teresa Samà, Alessandro Angelo Bisoffi, Marina Caputo, Valentina Bullara, Stefania Mai, Gillian Elisabeth Walker, Flavia Prodam, Paolo Marzullo, Gianluca Aimaretti and Loredana Pagano
The associative link relating insulin resistance (IR) and adipokines to the occurrence and phenotype of differentiated thyroid cancer (DTC) is unknown. The aim of this study was to evaluate the relationship between IR and adipokines in DTC patients, as compared with carriers of benign thyroid diseases (BTD) and healthy controls. This observational study enrolled 77 subjects phenotyped as DTC (N = 30), BTD (N = 27) and healthy subjects (N = 20). Each subject underwent preoperative analysis of anthropometric parameters, thyroid function and autoimmunity, insulin resistance (HOMA-IR) and levels of unacylated (UAG) and acylated ghrelin (AG), obestatin, leptin and adiponectin. Multivariate regression models were used to test the predictive role of metabolic correlates on thyroid phenotypes and DTC extension. The three groups showed similar age, gender distribution, smoking habit, BMI and thyroid parameters. Obestatin was significantly higher in DTC group compared to BTD (P < 0.05) and control subjects (P < 0.0001). DTC and BTD groups showed higher levels of UAG (P < 0.01) and AG (P < 0.05). Leptin levels were comparable between groups, whereas adiponectin levels were lower in DTC compared to BTD group (P < 0.0001) and controls (P < 0.01). In parallel, HOMA-IR was higher in DTC than BTD (P < 0.05) and control group (P < 0.01). Stepwise multivariable regression analysis showed that obestatin and UAG were independent predictors of DTC (P = 0.01 for both). In an analysis restricted to the DTC group, obestatin levels were associated with the absence of lymph node metastases (P < 0.05). Our results highlight a potential association between metabolic setting, circulating adipokines and thyroid cancer phenotype.