Partial Lipodystrophy Affecting the Extremities in a Young Woman With Autoimmune Polyglandular Syndrome 1.

Autoimmune polyglandular syndrome 1 (APS1) is an autosomal recessive disorder due to biallelic pathogenic variants in the autoimmune regulator (AIRE) gene that manifests with chronic mucocutaneous candidiasis, primary hypoparathyroidism, and adrenal insufficiency. We report a 39-year-old woman with APS1 who developed partial lipodystrophy during adulthood. She presented with diaper rashes, oral thrush, and tetany during infancy due to candidiasis and hypoparathyroidism. During childhood, she developed hypothyroidism, primary adrenal insufficiency, and ovarian insufficiency. At age 14, she received a sibling-matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At age 35, her serum triglycerides were 914 mg/dL (10.32 mmol/L) and she had loss of subcutaneous fat from the upper and lower extremities and hips. A whole-body dual-energy x-ray absorptiometry revealed lower-extremity fat at less than the first percentile. Whole-exome sequencing on DNA extracted from saliva revealed pathogenic variants, p.Leu28Pro and p.Arg257* in AIRE but none in the known lipodystrophy genes. Phage-immunoprecipitation-sequencing revealed the presence of autoantibodies to MAGEB1, MAGEB4, and RFX6, which have been previously reported in APS1. Our case suggests that patients with APS1 may develop partial lipodystrophy due to autoantibodies against novel adipocyte-expressed proteins. A causal relationship of high levels of autoantibodies in our patient to adipose tissue-expressed ODC1, NUCKS1, or FNBP1L and lipodystrophy remains uncertain.

The single-cell transcriptome of mTECs and CD4+ thymocytes under adhesion revealed heterogeneity of mTECs and a network controlled by Aire and lncRNAs.

To further understand the impact of deficiency of the autoimmune regulator (Aire) gene during the adhesion of medullary thymic epithelial cells (mTECs) to thymocytes, we sequenced single-cell libraries (scRNA-seq) obtained from Aire wild-type (WT) (Airewt/wt ) or Aire-deficient (Airewt/mut ) mTECs cocultured with WT single-positive (SP) CD4+ thymocytes. Although the libraries differed in their mRNA and long noncoding RNA (lncRNA) profiles, indicating that mTECs were heterogeneous in terms of their transcriptome, UMAP clustering revealed that both mTEC lines expressed their specific markers, i.e., Epcam, Itgb4, Itga6, and Casp3 in resting mTECs and Ccna2, Pbk, and Birc5 in proliferative mTECs. Both cocultured SP CD4+ thymocytes remained in a homogeneous cluster expressing the Il7r and Ccr7 markers. Comparisons of the two types of cocultures revealed the differential expression of mRNAs that encode transcription factors (Zfpm2, Satb1, and Lef1), cell adhesion genes (Itgb1) in mTECs, and Themis in thymocytes, which is associated with the regulation of positive and negative selection. At the single-cell sequencing resolution, we observed that Aire acts on both Aire WT and Aire-deficient mTECs as an upstream controller of mRNAs, which encode transcription factors or adhesion proteins that, in turn, are posttranscriptionally controlled by lncRNAs, for example, Neat1, Malat1, Pvt1, and Dancr among others. Under Aire deficiency, mTECs dysregulate the expression of MHC-II, CD80, and CD326 (EPCAM) protein markers as well as metabolism and cell cycle-related mRNAs, which delay the cell cycle progression. Moreover, when adhered to mTECs, WT SP CD4+ or CD8+ thymocytes modulate the expression of cell activation proteins, including CD28 and CD152/CTLA4, and the expression of cellular metabolism mRNAs. These findings indicate a complex mechanism through which an imbalance in Aire expression can affect mTECs and thymocytes during adhesion.

Corrigendum: Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency.

[This corrects the article DOI: 10.3389/fimmu.2011.00015.].

Reduction in mucosal-associated invariant T cells (MAIT) in APECED patients is associated with elevated serum IFN-γ concentration.

Mucosal-associated invariant T cells (MAIT) are innate-like lymphocytes enriched in mucosal organs where they contribute to antimicrobial defense. APECED is an inborn error of immunity characterized by immune dysregulation and chronic mucocutaneous candidiasis. Reduction in the frequency of circulating MAITs has been reported in many inborn errors of immunity, but only in a few of them, the functional competence of MAITs has been assessed. Here, we show in a cohort of 24 patients with APECED, that the proportion of circulating MAITs was reduced compared with healthy age and sex-matched controls (1.1% vs. 2.6% of CD3+ T cells; p < 0.001) and the MAIT cell immunophenotype was more activated. Functionally the IFN-γ secretion of patient MAITs after stimulation was comparable to healthy controls. We observed in the patients elevated serum IFN-γ (46.0 vs. 21.1 pg/mL; p = 0.01) and IL-18 (42.6 vs. 13.7 pg/mL; p < 0.001) concentrations. Lower MAIT proportion did not associate with the levels of neutralizing anti-IL-22 or anti-IL-12/23 antibodies but had a clear negative correlation with serum concentrations of IFN-γ, IL-18, and protein C-reactive protein. Our data suggest that reduction of circulating MAITs in patients with APECED correlates with chronic type 1 inflammation but the remaining MAITs are functionally competent.

Decreased T-cell response against latent cytomegalovirus infection does not correlate with anti-IFN autoantibodies in patients with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inborn error of immunity affecting both multiple endocrine organs and susceptibility to candidiasis, each with an autoimmune basis. Recently, high titer neutralizing anti-type I interferon (IFN) autoantibodies have been linked with increased severity of SARS-CoV-2 and varicella zoster virus infections in APECED patients. Examining immunity against cytomegalovirus (CMV), we found a higher prevalence of anti-CMV IgG antibodies in patients with APECED (N = 19) than in 44 healthy controls (90% vs 64%, p = 0.04); the similar difference in their IgG levels did not achieve significance (95 ± 74 vs 64 ± 35 IU/mL, ns.). In contrast, the frequency of CMV-specific T cells was lower (804 ± 718/million vs 1591 ± 972/million PBMC p = 0.03). We saw no correlations between levels of anti-CMV IgG and anti-IFN antibodies in APECED patients or in a separate cohort of patients with thymoma (n = 70), over 60% of whom also had anti-IFN antibodies. Our results suggest a dysregulated response to CMV in APECED patients and highlight immunodeficiency to viral infections as part of the disease spectrum.

Single-cell sequencing has revealed a more complex array of thymic epithelial cells.

Thymic epithelial cells participate in the maturation and selection of T lymphocytes. This review explores recent insights from single-cell sequencing regarding classifying thymic epithelial cells in both normal and neoplastic thymus. Cortical thymic epithelial cells facilitate thymocyte differentiation and contribute to positive selection. Medullary epithelial cells are distinguished by their expression of AIRE. Cells progress from a pre-AIRE state, containing precursors with cortical and medullary characteristics, termed junctional cells. Mature medullary epithelial cells exhibit promiscuous gene expression and after that downregulate AIRE mRNA. Post-AIRE cells can adopt a Hassall corpuscle-like phenotype or exhibit distinctive differentiation characteristics including tuft cells, ionocytes, neuroendocrine cells, and myoid cells.

Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 - A National Cohort Study.

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.

An uncommon presentation of autoimmune polyglandular syndrome type 1 (APS-1)-A case report.

Key Clinical Message: Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.

Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.

Insulin is a central autoantigen in the pathogenesis of T1D, and thymic epithelial cell expression of insulin under the control of the Autoimmune Regulator (Aire) is thought to be a key component of maintaining tolerance to insulin. In spite of this general working model, direct detection of this thymic selection on insulin-specific T cells has been somewhat elusive. Here, we used a combination of highly sensitive T cell receptor transgenic models for detecting thymic selection and sorting and sequencing of Insulin-specific CD4+ T cells from Aire-deficient mice as a strategy to further define their selection. This analysis revealed a number of unique t cell receptor (TCR) clones in Aire-deficient hosts with high affinity for insulin/major histocompatibility complex (MHC) ligands. We then modeled the thymic selection of one of these clones in Aire-deficient versus wild-type hosts and found that this model clone could escape thymic negative selection in the absence of thymic Aire. Together, these results suggest that thymic expression of insulin plays a key role in trimming and removing high-affinity insulin-specific T cells from the repertoire to help promote tolerance.

Small Intestinal Bacterial Overgrowth (SIBO), a clinically overdiagnosed entity? / Sobrecrecimiento bacteriano del intestino delgado (SIBO), ¿una entidad clínica sobrediagnosticada?

Small intestinal bacterial overgrowth (SIBO) is a clinical entity recognized since ancient times; it represents the consequences of bacterial overgrowth in the small intestine associated with malabsorption. Recently, SIBO as a term has been popularized due to its high prevalence reported in various pathologies since the moment it is indirectly diagnosed with exhaled air tests. In the present article, the results of duodenal/jejunal aspirate culture testing as a reference diagnostic method, as well as the characteristics of the small intestinal microbiota described by culture-dependent and culture-independent techniques in SIBO, and their comparison with exhaled air testing are presented to argue about its overdiagnosis.

Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, with the thymus playing a central role in establishing and maintaining this equilibrium. The induction of central immune tolerance in the thymus involves the elimination of self-reactive T cells, a mechanism essential for averting autoimmunity. Disruption of the thymic T cell selection mechanisms can lead to the development of autoimmune diseases. In the dynamic microenvironment of the thymus, T cell migration and interactions with thymic stromal cells are critical for the selection processes that ensure self-tolerance. Thymic epithelial cells are particularly significant in this context, presenting self-antigens and inducing the negative selection of autoreactive T cells. Further, the synergistic roles of thymic fibroblasts, B cells, and dendritic cells in antigen presentation, selection and the development of regulatory T cells are pivotal in maintaining immune responses tightly regulated. This review article collates these insights, offering a comprehensive examination of the multifaceted role of thymic tissue homeostasis in the establishment of immune tolerance and its implications in the prevention of autoimmune diseases. Additionally, the developmental pathways of the thymus are explored, highlighting how genetic aberrations can disrupt thymic architecture and function, leading to autoimmune conditions. The impact of infections on immune tolerance is another critical area, with pathogens potentially triggering autoimmunity by altering thymic homeostasis. Overall, this review underscores the integral role of thymic tissue homeostasis in the prevention of autoimmune diseases, discussing insights into potential therapeutic strategies and examining putative avenues for future research on developing thymic-based therapies in treating and preventing autoimmune conditions.

Compilation of regulations and procedures for monitoring filamentous fungi in hospital environments.

Air and surfaces in the hospital environment are a potential source of exposure to filamentous fungi (FF) that could cause invasive fungal diseases (IFD) in severely immunocompromised patients. The prevalent FF in IFD are species from the genera Aspergillus, Fusarium, Scedosporium, and those within the order Mucorales. We have compiled regulations and described the procedures used in the clinical mycology laboratory to assess the presence of FF in areas at risk for the development of IFD. The infection control committees of each establishment implement hospital policies to regulate and control processes aimed at preventing infections. Fungal load monitoring is an important step in this process to validate air quality in order to ensure a clean and protected environment for severely immunocompromised patients.

Exploring Chronic Hypocalcemia: Insights into Autoimmune Polyglandular Syndrome Type 1-A Case Study and Literature Review.

Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions.

Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance.

Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by the nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations, namely Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21, which attracts developing thymocytes to the medullary region. Here, we report that CCL21+ mTECs and Aire+ mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detect cooperation for self-tolerance between Aire and Fezf2, the latter of which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.

Early recognition of the APECED rash can accelerate the diagnosis of APECED.

Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) is a monogenic autoimmune disease most often resulting from biallelic loss-of-function variants in the autoimmune regulator (AIRE) gene. Although typically characterized by the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, we have recently reported that the clinical spectrum of the syndrome is far broader that previously described and that incorporation of an adjunct triad of APECED rash, autoimmune enteritis-associated intestinal dysfunction, and enamel hypoplasia in the classic triad manifestations could lead to earlier diagnosis. Among the adjunct triad manifestations, APECED rash occurs in 66% of American APECED patients by age 3, most often developing in the first year of life. Here, we describe the clinical and histological features of protracted APECED rash manifesting together with recurrent mucocutaneous candidiasis as the first two disease components of APECED in a 10-month-old girl.

Progressive Impairment of Prepubertal Growth in Children With APECED.

CONTEXT: Subjects with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) have subnormal adult height. There are several potential APECED-related risk factors for suboptimal height attainment during childhood. OBJECTIVE: To determine the growth patterns in children with APECED. DESIGN: Retrospective longitudinal study. SETTING: The Finnish national APECED cohort. PATIENTS: 59 children with APECED. MAIN OUTCOME MEASURES: Length/height and weight z-scores from birth to the end of prepuberty. RESULTS: Collectively, 59 children [30 (51%) girls] were included. Their median birth weight z-score (-0.60) was below the population average; 12 (20%) patients were born small for gestational age. Height attainment progressively declined from birth until the end of prepuberty (z-score -1.95), whereas weight-for-height z-score did not (+0.26). Of the 59 patients, 38 (64%) had all height z-scores below 0 during prepuberty, and seven (12%) had z-scores below -2.0. Age at the end of prepuberty, number of APECED manifestations, duration of glucocorticoid treatment, and growth hormone deficiency correlated negatively with height z-score at the end of prepuberty (p < 0.0001; p = 0.041; p = 0.013; p = 0.034, respectively). CONCLUSIONS: Children with APECED had a progressive growth impairment from birth through prepuberty. Multiple predisposing risk factors were recognized, including disease severity and growth hormone deficiency. Timely interventions are needed to ensure optimal height attainment and new treatment options need to be developed.

Lessons from prospective longitudinal follow-up of a French APECED cohort.

BACKGROUND: APECED syndrome is a rare disease caused by biallelic mutations of the AIRE gene, usually presenting with the triad "hypoparathyroidism-adrenal failure-chronic mucocutaneous candidiasis (CMC)" and non-endocrine manifestations. The aim of this study was to determine the molecular profile of the AIRE gene, the prevalence of rare manifestations and to characterize immunological disturbances in a French cohort. PATIENTS AND METHODS: A national, multicenter prospective observational study to collect genetic, clinical, biological and immunological data (NCT03751683). RESULTS: 25 patients (23 families) were enrolled. Eleven distinct AIRE variants were identified, two of which were not previously reported: an intronic variant, c.653-70G > A, and a c.1066del (p.Arg356GlyfsX22) variant (exon 9). The most common was the Finnish variant c.769C > T (16 alleles), followed by the variant c.967_979del13 (15 alleles), which seemed associated with a less severe phenotype. 17/25 patients were homozygote. The median number of clinical manifestations was seven; 19/25 patients presented with the hypoparathyroidism-adrenal failure-CMC triad, 8/13 showed pulmonary involvement, 20/25 had ectodermal dystrophy, 8/25 had malabsorption, and 6/23 had asplenia. Fifteen out of 19 patients had NK cell lymphopenia with an increase in CD4+ and CD8+ T lymphocytes and an age-dependent alteration of B lymphocyte homeostasis compared with matched controls (p < 0.001), related to the severity of the disease. All tested sera (n = 18) were positive for anti-interferon-α, 15/18 for anti-interleukin-22 antibodies, and 13/18 for anti-interleukin-17F antibodies, without clear phenotypic correlation other than with CMC. CONCLUSION: This first prospective cohort showed a high AIRE genotype variability, with two new gene variants. The prevalence of potentially life-threatening non-endocrine manifestations, was higher with systematic screening. These manifestations could, along with age-dependent B-cell lymphopenia, contribute to disease severity. Systematic screening for all the manifestations of the syndrome would allow earlier diagnosis, supporting vaccination, and targeted therapeutic approaches.

Solitary fibrous tumor of the pleura with air cystic component.

We present an uncommon case of a solitary fibrous tumor of the pleura with the appearance of an air-containing cystic mass. We discuss the differential diagnosis through the imaging findings, the hypothetical origins of the air component, and the possible relationship between the air component and the aggressivity of the tumor.

Cohort profile: The Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study.

BACKGROUND: The Children's Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study is a prospective cohort study of environmental influences on respiratory health in a rural, southeastern region of California (CA), which aims to longitudinally examine the contribution of a drying saline lake to adverse health impacts in children. OBJECTIVES: This cohort was established through a community-academic partnership with the goal of assessing the health effects of childhood exposures to wind-blown particulate matter (PM) and inform public health action. We hypothesize that local PM sources are related to poorer children's respiratory health. POPULATION: Elementary school children in Imperial Valley, CA. DESIGN: Prospective cohort study. METHODS: Between 2017 and 2019, we collected baseline information on 731 children, then follow-up assessments yearly or twice-yearly since 2019. Data have been collected on children's respiratory health, demographics, household characteristics, physical activity and lifestyle, via questionnaires completed by parents or primary caregivers. In-person measurements, conducted since 2019, repeatedly assessed lung function, height, weight and blood pressure. Exposure to air pollutants has been assessed by multiple methods and individually assigned to participants using residential and school addresses. Health data will be linked to ambient and local sources of PM, during and preceding the study period to understand how spatiotemporal trends in these environmental exposures may relate to respiratory health. PRELIMINARY RESULTS: Analyses of respiratory symptoms indicate a high prevalence of allergies, bronchitic symptoms and wheezing. Asthma diagnosis was reported in 24% of children at enrolment, which exceeds both CA state and US national prevalence estimates for children. CONCLUSIONS: The Children's AIRE cohort, while focused on the health impacts of the drying Salton Sea and air quality in Imperial Valley, is poised to elucidate the growing threat of drying saline lakes and wind-blown dust sources to respiratory health worldwide, as sources of wind-blown dust emerge in our changing climate.

Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis.

Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%-93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.