Elizaveta M. Orlova's research while affiliated with Endocrinology Research Centre and other places

Publications (44)

Article
Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein Perilipin-1 (PLIN1)...
Article
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The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target i...
Article
Autoimmune hepatitis is a chronic inflammatory liver disease of unknown etiology; the prevalence of juvenile autoimmune hepatitis is unknown. Autoimmune hepatitis occurs in 10–20% of patients with type 1 autoimmune polyendocrine syndrome, a rare (orphan) disease, which is characterized by a clinical triad in 70–100% of cases: chronic mucocutaneous...
Preprint
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Background: Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Methods: Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte specific lipid droplet protei...
Article
Full-text available
Context Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED or APS-1) has a severe, unpredictable course. Autoimmunity and disease components may affect fertility and predispose to maternal and fetal complications, but pregnancy outcomes remain unknown. Objective To assess fetal and maternal outcomes and course of clinical APECE...
Article
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVI...
Article
21-hydroxylase (21-OH) is the main antigen of the adrenal cortex, so the determination of antibodies (Ab) to 21-OH can help in the diagnosis and prognosis of chronic primary adrenal insufficiency (CPAI). Purpose of the study: evaluation of the relevance of Ab to 21-OH for the diagnosis and prediction of autoimmune CPAI. Materials and methods of res...
Article
Cushing’s disease (CD) is a multisystem disorder of a cortisol excess caused by ACTH -secreting pituitary tumor (corticotropinoma). CD in children is due to somatic or germline mutations with the late onset causing multiple endocrine tumors. If not treated, hypercortisolism leads to severe decrease in quality of life and life-threating conditions....
Article
Primary adrenal insufficiency is manifested by a deficiency of adrenal cortex hormones and can lead to a life-threatening condition. Early diagnosis is key to patient survival. Auto-antibodies to one of the adrenal steroidogenesis enzymes, 21-hydroxylase, are an immunological marker of autoimmune adrenal insufficiency. On the one hand, the study of...
Article
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The disorders of sex development (DSD) 46,XY may be caused by mutations in a number of genes involved in the gonadal differentiation. The XY sex inversion can be also due to disturbances at the level of mitogen-activated protein kinase (MAPK) kinase kinase 1 gene (MAP3K1) and MAPK-signaling pathway. During the last decade, the involvement of the MA...
Article
Full-text available
The disorders of sex development (DSD) 46,XY may be caused by mutations in a number of genes involved in the gonadal differentiation. The XY sex inversion can be also due to disturbances at the level of mitogen-activated protein kinase (MAPK) kinase kinase 1 gene (MAP3K1) and MAPK-signaling pathway. During the last decade, the involvement of the MA...
Article
Full-text available
Background. Autoimmune polyglandular syndrome type 1 (APS type 1) is a rare inherited autoimmune disease caused by mutations in AIRE gene (autoimmune regulator) and characterized by list of components. Diabetes mellitus (DM) can be one of components of this disease. Aims. To show frequency of DM in patients with APS type 1 in Russia, to describe c...
Article
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Синдром МакКьюна—Олбрайта—Брайцева (МОБ) — редкое генетическое заболевание, в основе которого лежат соматические мутации в гене GNAS. Клинические признаки заболевания включают пятна цвета «кофе с молоком», фиброзную дисплазию и гиперфункцию эндокринных желез. Соматический характер мутации определяет вариабельность проявлений синдрома: от легких фор...
Article
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Гипопаратиреоз является одним из основных проявлений аутоиммунного полигландулярного синдрома 1-го типа. Препаратами выбора для лечение гипопаратиреоза любой этиологии на сегодняшний день являются гидроксилированные препараты витамина D. Лечение препаратами витамина D позволяет нормализовать и поддерживать нормальный уровень кальция достаточно эффе...
Article
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Протяженные или «сопряженные» генные синдромы (CGS) — заболевания, обусловленные хромосомными нарушениями: делециями, дубликациями или другими сложными перестройками, которые приводят к нарушениям дозы гена. Вначале (до выяснения их хромосомной природы) они могут диагностироваться как моногенные заболевания в зависимости от ведущего клинического си...
Article
Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. Objective: T...
Article
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Эндогенный гиперкортицизм у детей первого года жизни встречается крайне редко. Среди причин синдрома Кушинга в раннем детстве — объемные образования надпочечников и двусторонняя гиперплазия надпочечников. АКТГ-независимый гиперкортицизм за счет двусторонней узелковой гиперплазии надпочечников у детей первых месяцев жизни чаще всего обусловлен синдр...
Article
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Congenital hypopituitarism is usually diagnosed in children with growth retardation. Severe life-threatening hypoglycemia and cholestasis can be early manifestations of hypopituitarism in neonates. The pituitary stalk interruption syndrome revealed by MRI confirms the diagnosis of congenital hypopituitarism. We report six cases of children admitted...
Article
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Обоснование. Псевдогипопаратиреоз (ПГП) — группа редких заболеваний, связанная с резистентностью к паратгормону (ПТГ). ПГП характеризуется генетической гетерогенностью и клиническим полиморфизмом. Помимо синдрома гипокальциемии на фоне резистентности к ПТГ, для ПГП характерны особенности фенотипа и резистентность к другим гормонам (ТТГ, ЛГ, ФСГ, ГР...
Article
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McCune-Albright syndrome (MAS) is a rare multisystem disorder, classically defined by the clinical triad of fibrous dysplasia of bones (FD), café-au-lait skin spots, precocious puberty (PP) and other hyperfunctioning endocrinopathies. Diagnosis can be made if there are at least 2 of the 3 classical features. It is caused by somatic mutations of the...
Article
Hypoparathyroidism is one of major components of autoimmune polyglandular syndrome type 1 (APS type 1) with a prevalence 73-83%. The protein NALP5 has been described previously as an antigen of parathyroid glands. Aim-to investigate antibodies against NALP5 in patients with APS type 1. Material and methods. Seventy nine patients with APS type 1 wer...
Article
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Introduction. Compromised fertility is one of the main health-related problems encountered by men suffering from 21-hydroxylase deficient congenital adrenal hyperplasia (CAH). This condition can be attributed either to the disease itself or to the presence of the testicular adrenal rest tissue (TART). The dysfunction of the reproductive system can...
Article
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This study was designed to ascertain the role of anti-interferon (IFN)-ω and -α2 antibodies (AB) in diagnostics of type 1 autoimmune polyglandular syndrome (APS-1) and evaluate specificity and sensitivity of the HEK-Blue cells method used to detect these antibodies. The study included 34 patients presenting with APS-1 and 21 patients with focal alo...
Article
The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutati...
Article
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We have evaluated the prevalence of the ectopic testicular adrenal rest tissue (TART) among 71 patients at the age varying from 1 to 19 years and compared the visualization techniques (ultrasound examination, MRI) employed to diagnose TART. This condition was revealed in 14.1% of the patients (10/71). One of them presented with the simple virile (S...
Article
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Pseudo-hypothyroidism (PHP) is a rare genetic disorder that manifests itself in the form of disturbances of phosphorus and calcium metabolism due to parathyroid hormone (PTH) resistance. The clinical variant of PHP depends not only on PTH resistance: there is a phenotype attributable to multi-hormonal resistance. PTH resistance is associated with t...
Article
Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and oth...
Article
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-...
Article
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-...
Article
Almost all patients with autoimmune polyendocrine syndrome (APS)-I have high titer neutralizing autoantibodies to type I interferons (IFN), especially IFN-ω and IFN-α2, whatever their clinical features and onset-ages. About 90 % also have antibodies to interleukin (IL)-17A, IL-17F and/or IL-22; they correlate with the chronic mucocutaneous candidia...
Article
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Familial isolated glucocorticoid deficiency (FIGD) is a rare form of primary adrenal insufficiency associated with the resistance of the adrenal cortex to the action of ACTH. This pathology manifests itself in the form of cortisol deficiency despite the normal mineralocorticoid function. Approximately 50% of all FIGD cases are attributable to mutat...
Article
A 26-year-old female with the classic major and minor components of autoimmune polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia. Treatment with 1.5 g/d mycofenolate mofetil for 3 months failed to restore erythroid production. Treatment with cyclosporine A produced a good partial response but led to renal toxicity and was...
Article
Carney complex is a rare autosomal dominant condition that manifests itself as a combination of lentiginosis, heart and skin myxomas, primary pigmented micronodular adrenocortical hyperplasia with ACTH-independent hypercorticism, calcifying Sertoli cell testicular tumours, schwannomas, thyroid and breast tumours, and other neoplasms. A total of 400...
Article
Carney complex is a rare hereditary syndrome characterized by an autosomal-dominant mode of inheritance and associated with multiple neoplasias affecting endocrine organs. The typical manifestations of this syndrome include pigmented micronodular adrenal dysplasia, lentiginosis, heart and skin myxomas, giant cell sertoliomas, and some other neoplas...
Article
The idiopathic form of premature sexual development (PSD) is the commonest variety among the central forms of PSD (accounting for 30 to 70% of the total). It occurs primarily in the girls. The prevalence of hypothalamic hamartoma (HH) as a cause of premature sexual development is on the whole lower, but it is most frequently diagnosed in the childr...
Article
Carcinoid syndrome develops as a sequel of enhanced secretion of vasoactive substances from neuroendocrine tumours (NET). Somatostatinoma is an extremely rare variant of NET that manifests itself in cholelithiasis, steatorea, and diabetes mellitus. Somatostatinoma is usually diagnosed in adult subjects. Carcinoid syndrome is not a typical consequen...
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Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, electrolyte disorders like a hypernatriemia, and neural tumor (ROHHADNET) is a newly described syndrome that can cause cardioresperitory arrests and death. It mimics several endocrine disorders or genetic obesity syndromes during early childhood and is associated with...
Article
Adrenogenital syndrome is a group of pathological conditions with autosomal recessive inheritance underlain by the deficit of one of the enzymes involved in cortisol biosynthesis. The first clinical reports of patients with adrenogenital syndrome date back to the XIXth century. The literature of the early XXth century offers comprehensive clinical...
Article
22 children with tumors or other surgical diseases of the adrenal glands were operated on laparoscopically. Children aged from 5 months to 17 years. Operation lengths varied from 45 to 190 minutes. There were no lethal outcomes, conversions and serious complications of the procedure. Authors consider the laparoscopic adrenalectomy to be the safe an...
Article
Autoimmune polyglandular syndrome type 1 (APS-1) (OMIM 240300) is a rare autosomal recessive disorder associated with three major manifestations: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. There are, however, multiple minor components of APS-1 that induce significant phenotype variability. Subsequently, the di...
Article
Congenital adrenal hypoplasia is a rare clinical variant of primary adrenal insufficiency. Two forms of this disease are known, one of which is inherited in an autosomal recessive manner (including IMAGe syndrome - a combination of adrenal hypoplasia with intrauterine growth retardation, metaphysical dysplasia and abnormal genital structure, OMIM 3...

Citations

... found that these patients did not suffer a statistically higher rate of miscarriage, pregnancy complications, or fetal growth restriction relative to the general population; however, of the five patients with oocyte donation, one suffered a stillbirth secondary to gestational hypertension and a uterus anomaly. 73 Perhaps APS-1 patients with severe symptomatology, including ovarian insufficiency necessitating oocyte donation, are more likely to suffer pregnancy complications. A Russian case study described two pregnant APS-1 patients on appropriate hormone replacement therapy who suffered threatened miscarriages in the first trimester, fetoplacental insufficiency, and fetal growth restriction. ...
... These findings established the crucial role of type I IFNs in fending off SARS-CoV-2 (9). Moreover, auto-Abs neutralizing high concentrations (10 ng/mL in plasma diluted 1/10) of IFN-α2 and/or IFN-ω were found in at least 10% of individuals with critical COVID-19 (10), an observation replicated in various regions of the world (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Patients with autoimmune polyendocrine syndrome type I (APS-1) harbor these neutralizing auto-Abs from early childhood and are at high risk of life-threatening COVID-19 (20,21). ...
... As mentioned above, the AIRE transcription factor has an important role in maintaining self-tolerance and preventing autoimmunity (78,(170)(171)(172)(173). The polyautoimmune syndrome resulting from AIRE mutations is a rare autosomal recessive disease called autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED) or autoimmune polyendocrine syndrome type-1 (174)(175)(176). ...
... It is important to note that an immunological study confirmed the results of AIRE sequencing: patients were tested for the Ab to type I interferons ω-and α 2 -. These markers can be found in most patients with APS-1 [37][38][39] A c c e p t e d M a n u s c r i p t 17 and highly specific (Ab to ω-interferon 100%; to α 2 -interferon, 99.9%) methods for APS-1 diagnosis [40]. The formation of these Abs is presumably due to a violation of the negative selection of T-lymphocytes, specific for type I interferons, in the thymus [41]. ...
... Гораздо реже встречаются образования из остаточной надпочечниковой ткани в яичниках у женщин. Их частота менее 0,1% среди всех образований яичников [1][2][3][4]. Данные аутопсий показывают, что остаточная надпочечниковая ткань более часто встречается в чревном сплетении, яичках, широкой связке матки, нежели в яичниках, что может обусловливать редкость развития OART. Кроме того, TART чаще диагностируются у мужчин, так как могут обнаружиться пальпаторно или вызывать болевой синдром [5][6][7][8]. ...
... Of note in parents of APECED patients harboring heterozygous AIRE mutations, immunological dysregulation was detected in the peripheral blood by elevated levels of IgA and activated T lymphocytes [28]. Furthermore, AIRE gene monoallelic mutations located in the first plant homeodomain (PHD1) zinc finger with autosomal dominant inheritance were found associated with autoimmune diseases characterized by a later onset, milder phenotype and reduced penetrance; however, manifestations in these conditions did not satisfy the clinical diagnostic criteria for APECED [47]. A milder phenotype was reported in a 'non-classical late onset' APECED due to a dominant-negative monoallelic mutation (G228W) located in the SAND domain of the AIRE gene in an Italian family with high incidence of Hashimoto's thyroiditis (HT) [48]. ...
... гиперплазия надпочечников ( МикГН) -двустороннее поражение надпочечников, приводящее к избыточной продукции кортизола. МикГН является редкой патологией и составляет 0,6-1,9% АКТГ-независимого гиперкортицизма (АКТГ -адренокортикотропный гормон), из которых около 70% -семейные детерминированные формы [1,2]. По данным ретроспективных исследований, заболеваемость превалирует у лиц молодого и среднего возраста (24,2±11,0 года), патология встречается чаще у женщин, чем у мужчин, соотношение 2,3:1 [3]. ...
... после отмены терапии. Обзор научных публикаций последних лет подтверждает эффективность использования Трипторелина у детей с ЦППС [2,9,12]. ...
... High titers of these antibodies were detected in all patients with APS-1, but these antibodies were not found in patients with APS-2 or isolated autoimmune diseases [29,32]. Subsequently, numerous studies of autoantibodies to IFN-α and -ω demonstrated them as highly specific and highly sensitive markers of APS-1 [33,34]. ...
... The HEK-Blue IFN-α/β system has been employed for research purposes using in vitro infection models, mainly to detect or quantify the production of bioactive IFN-I during viral or bacterial infections [24][25][26][27][28][29][30]. This system has also been proposed as a diagnostic tool for the indirect identification of neutralizing autoantibodies against IFN-I in some autoimmune diseases [31]. ...