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

Weiler, Fernanda Guimarães; Peterson, Pärt; Costa‐Carvalho, Beatriz Tavares; Dorna, Mayra de Barros; Correia-Deur, Joya Emilie de Menezes; Sader, Soraya Lopes; Espíndola-Antunes, Daniela; Guerra, Gil; Silva, Magnus R. Dias da; Lazaretti-Castro, Marise

doi:10.1016/j.clim.2018.09.012

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…IFNωAbs were found to be the best serological marker of APS-1 regardless of the comorbidities and the duration of the syndrome as previously described [4,20,[33][34][35]48]. This confirms that IFNωAbs are a diagnostic marker for APS-1 and can be particularly helpful in early diagnosis in patients presenting with a single manifestation of APS-1 [4].…”

Section: Discussionsupporting

confidence: 84%

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

Garelli

Costa

Sabbadin

et al. 2021

J Endocrinol Invest

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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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Section: Discussionsupporting

confidence: 84%

“…A similar clinical presentation has been described in European populations [5,15]. However, in the cohorts of American patients [17,35], non-major component diseases were noted at APS-1 onset in 40-80% of the cases.…”

Section: Discussionsupporting

confidence: 74%

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

Garelli

Costa

Sabbadin

et al. 2021

J Endocrinol Invest

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“…In Table 2, the prevalence of AAD and APOI in various APS1 patient cohorts is reported, with the specification of their ethnic backgrounds (15,144,153,(181)(182)(183)(184)(185)(186)(187)(188)(189)(190)(191)(192)(193)(194)(195)(196)(197). AAD prevalence can sometimes be influenced by the mean patient age, for example, in Saudi patients with APS1 described by Bin-Abbas et al (193).…”

Section: Prevalence Of Aps1-associated Aad and Apoimentioning

confidence: 99%

Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

2021

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The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.

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“…In addition, novel autoantibodies against lung-specific bactericidal/permeabilityincreasing fold-containing protein B1 (BPIFB1) and the potassium channel regulator protein (KCNFG), have been linked to onset of autoimmune pneumonitis in disorders of central T-cell tolerance (APECED, RAG deficiency, and thymoma) [39]. It is intriguing that presence of anticytokine antibodies are also proposed as markers of prognosis in APECED, as they noted negative correlation of anti-IFNa antibodies and the incidence of T1DM [40,41].…”

Section: Patients With Pid Tend To Have Broad Selection Of Autoantibodies As Seen In Rag Deficiency With Aics [20 Andmentioning

confidence: 99%

Autoimmunity as a continuum in primary immunodeficiency

Walter

Ayala

Milojevic³

2019

Current Opinion in Pediatrics

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Purpose of review Primary immunodeficiency disorders (PIDs) are no longer defined by infections alone. First clinical sign or sequelae of PID may include autoimmunity, such as cytopenias, arthritis or enteropathy. This review addresses the latest in multidisciplinary approaches for expanding clinical phenotypes of PIDs with autoimmunity, including new presentations of known entities and novel gene defects. We also discuss diagnostic tools for identifying the distinct changes in immune cells subsets and autoantibodies, mechanistic understanding of the process, and targeted treatment and indications for hematopoietic stem-cell transplantation (HSCT). Recent findingsIn the past years, increased awareness and use of genetic screening, confirmatory functional studies and immunological biomarkers opened the door for early recognition of PIDs among patients with autoimmunity. Large cohort studies detail the clinical spectrum and treatment outcome of PIDs with autoimmunity with specific immune genes (e.g., CTLA4, LRBA, PI3Kd, NFKB1, RAG). The benefit of early recognition is initiation of targeted therapies with precise re-balancing of the dysregulated immune pathways (e.g., biologicals) or definitive therapy (e.g., HSCT). SummaryClinical presentation of patients with PID and autoimmunity is highly variable and requires in-depth diagnostics and precision medicine approaches.

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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

Cited by 10 publications

References 45 publications

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

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

Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

Autoimmunity as a continuum in primary immunodeficiency

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