Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

Objective 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. Design 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. Methods Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Results 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. Conclusions 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.

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Autoimmune polyglandular syndrome type 1 and eye damage

Acta biomedica scientifica ◽

10.29413/abs.2021-6.6-1.3 ◽

2021 ◽

Vol 6 (6-1) ◽

pp. 19-30

Author(s):

L. Yu. Khamnueva ◽

T. N. Iureva ◽

L. S. Andreeva ◽

E. V. Chugunova

Keyword(s):

Adrenal Insufficiency ◽

Clinical Manifestations ◽

Autosomal Recessive Inheritance ◽

Antigen Expression ◽

Pathological Process ◽

Syndrome Type ◽

Autoimmune Polyendocrine Syndrome ◽

Endocrine Organs ◽

Eye Damage

Autoimmune polyendocrine syndrome type 1 (APS type 1) is a disease characterized by a variety of clinical manifestations resulting from the involvement of multiple endocrine and non-endocrine organs in the pathological process. APS type 1 is a rare genetically determined disease with autosomal recessive inheritance. Mutations in the autoimmune regulator gene (AIRE) lead to a disruption of the mechanism of normal antigen expression and the formation of abnormal clones of immune cells, and can cause autoimmune damage to organs. Within APS type 1, the most common disorders are primary adrenal insufficiency, hypoparathyroidism, and chronic candidiasis. Some understudied clinical manifestations of APS type 1 are autoimmune pathological processes in the eye: keratoconjunctivitis, dry eye syndrome, iridocyclitis, retinopathy, retinal detachment, and optic atrophy. This review presents the accumulated experimental and clinical data on the development of eye damage of autoimmune nature in APS type 1, as well as the laboratory and instrumental methods used for diagnosing the disease. Changes in the visual organs in combination with clinical manifestations of hypoparathyroidism, adrenal insufficiency and candidiasis should lead the clinical doctor to suspect the presence of APS type 1 and to examine the patient comprehensively. Timely genetic counselling will allow early identifi cation of the disease, timely prescription of appropriate treatment and prevention of severe complications.

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Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01585-6 ◽

2021 ◽

Author(s):

S. Garelli ◽

M. Dalla Costa ◽

C. Sabbadin ◽

S. Barollo ◽

B. Rubin ◽

...

Keyword(s):

Gene Mutations ◽

Premature Menopause ◽

Chronic Mucocutaneous Candidiasis ◽

Syndrome Type ◽

Inherited Disease ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Polyendocrine Syndrome ◽

Autoimmune Conditions

Abstract Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

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The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers

Clinical Immunology ◽

10.1016/j.clim.2018.09.012 ◽

2018 ◽

Vol 197 ◽

pp. 231-238 ◽

Cited By ~ 3

Author(s):

Fernanda Guimarães Weiler ◽

Pärt Peterson ◽

Beatriz Tavares Costa-Carvalho ◽

Mayra de Barros Dorna ◽

Joya Emilie Correia-Deur ◽

...

Keyword(s):

Clinical Features ◽

Tertiary Care ◽

Syndrome Type ◽

Autoimmune Polyendocrine Syndrome ◽

Tertiary Care Centers ◽

Brazilian Cohort ◽

New Mutations

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Autoimmune polyendocrine syndrome type 1: case report and review of literature

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302012000100009 ◽

2012 ◽

Vol 56 (1) ◽

pp. 54-66 ◽

Cited By ~ 19

Author(s):

Fernanda Guimarães Weiler ◽

Magnus R. Dias-da-Silva ◽

Marise Lazaretti-Castro

Keyword(s):

Autosomal Recessive ◽

Clinical Course ◽

Clinical Manifestations ◽

Autosomal Recessive Disorder ◽

Syndrome Type ◽

Adrenal Failure ◽

Review Of Literature ◽

Autoimmune Polyendocrine Syndrome

Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.

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Oralfacialdigital syndrome type 1: a review

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v14i2.22781 ◽

2015 ◽

Vol 14 (2) ◽

pp. 130-134

Author(s):

Amith Adyanthaya ◽

Soniya Adyanthaya

Keyword(s):

Molecular Genetics ◽

Clinical Features ◽

Medical Science ◽

Clinical Manifestations ◽

Pleiotropic Effect ◽

Type I ◽

Syndrome Type ◽

Organ Systems

The oralfacialdigital syndromes result from the pleiotropic effect of a morphogenetic impairment affecting almost invariably the mouth, face and digits. Other organ systems can be involved, defining specific types of OFDS. To date, 13 types have been distinguished based on characteristic clinical manifestations. The oralfacialdigital syndrome type I is discussed in detail with emphasis on clinical features, molecular genetics and diagnosis.Bangladesh Journal of Medical Science Vol.14(2) 2015 p.130-134

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Inflammation-Related Carcinogenesis: Lessons from Animal Models to Clinical Aspects

Cancers ◽

10.3390/cancers13040921 ◽

2021 ◽

Vol 13 (4) ◽

pp. 921

Author(s):

Futoshi Okada ◽

Runa Izutsu ◽

Keisuke Goto ◽

Mitsuhiko Osaki

Keyword(s):

Animal Models ◽

Tissue Injury ◽

Economic Status ◽

Gene Mutations ◽

Inflammatory Cells ◽

The Body ◽

Clinical Aspects ◽

Promote Cell Proliferation ◽

Organ Specific ◽

Altered Gene

Inflammation-related carcinogenesis has long been known as one of the carcinogenesis patterns in humans. Common carcinogenic factors are inflammation caused by infection with pathogens or the uptake of foreign substances from the environment into the body. Inflammation-related carcinogenesis as a cause for cancer-related death worldwide accounts for approximately 20%, and the incidence varies widely by continent, country, and even region of the country and can be affected by economic status or development. Many novel approaches are currently available concerning the development of animal models to elucidate inflammation-related carcinogenesis. By learning from the oldest to the latest animal models for each organ, we sought to uncover the essential common causes of inflammation-related carcinogenesis. This review confirmed that a common etiology of organ-specific animal models that mimic human inflammation-related carcinogenesis is prolonged exudation of inflammatory cells. Genotoxicity or epigenetic modifications by inflammatory cells resulted in gene mutations or altered gene expression, respectively. Inflammatory cytokines/growth factors released from inflammatory cells promote cell proliferation and repair tissue injury, and inflammation serves as a “carcinogenic niche”, because these fundamental biological events are common to all types of carcinogenesis, not just inflammation-related carcinogenesis. Since clinical strategies are needed to prevent carcinogenesis, we propose the therapeutic apheresis of inflammatory cells as a means of eliminating fundamental cause of inflammation-related carcinogenesis.

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Characterization of the clinical and genetic spectrum of autoimmune polyendocrine syndrome type 1 in Chinese case series

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01933-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ya-Bing Wang ◽

Ou Wang ◽

Min Nie ◽

Yan Jiang ◽

Mei Li ◽

...

Keyword(s):

Case Series ◽

Pure Red Cell Aplasia ◽

Hereditary Disease ◽

Chinese Patients ◽

Chronic Mucocutaneous Candidiasis ◽

Syndrome Type ◽

Myeloproliferative Disease ◽

College Hospital ◽

Autoimmune Polyendocrine Syndrome

Abstract Background Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital. Results In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison’s disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1. Conclusion We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.

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Acquired pure red cell aplasia and T cell large granular lymphocytic leukaemia in patients with autoimmune polyglandular syndrome type 1

BMC Medical Genomics ◽

10.1186/s12920-020-00866-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jing Ruan ◽

Xuan Wang ◽

Xianyong Jiang ◽

Miao Chen

Keyword(s):

Lymphocytic Leukaemia ◽

Pure Red Cell Aplasia ◽

Chronic Diarrhoea ◽

Syndrome Type ◽

Red Cell ◽

Recurrent Pneumonia ◽

Red Cell Aplasia ◽

Autoimmune Polyendocrine Syndrome ◽

Immunological Mechanisms

Abstract Background Pure red cell aplasia (PRCA) and large granular lymphocytic leukaemia (LGLL) are very rare complications of autoimmune polyendocrine syndrome type 1 (APS1). Here, we report a case of APS1 with PRCA and LGLL. Previous cases were reviewed, and possible mechanisms are discussed. Case presentation A 31-year-old female presented with anaemia and was diagnosed with PRCA in our centre. She also had hypoparathyroidism for 24 years, premature ovarian failure for 10 years, osteoporosis for 5 years, recurrent pneumonia with bronchiectasis for 4 years and chronic diarrhoea for 1 year. Boosted whole-exome analysis showed AIRE heterozygous mutations, confirming the diagnosis as APS1. LGLL was diagnosed during follow-up. The PRCA responded well to glucocorticoid. treatment Conclusion AIRE is causally related to the development of LGLL and consequent PRCA, which may be due to some immunological mechanisms.

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