Immunophenotypic Characterisation of Peripheral Blood Lymphocytes in Autoimmune Polyglandular Syndrome Type 1: Clinical Study and Review of the Literature

Perniola, Roberto; Lobreglio, Giambattista; Rosatelli, Maria Cristina; Pitotti, Elena; Accogli, Elisa; Rinaldis, Corrado De

doi:10.1515/jpem.2005.18.2.155

Cited by 27 publications

(35 citation statements)

References 32 publications

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“…In a recent study, a cohort of 24 Finnish adult APECED patients was shown to have a significant lymphocytosis in peripheral blood (15); similar results were previously reported from pediatric and adolescent APECED patients (16). Prompted by these observations, we have studied the homeostasis of the circulating T cell population in APECED patients.…”

supporting

confidence: 63%

IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy

Laakso

Kekäläinen

Rossi

et al. 2011

The Journal of Immunology

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Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a monogenic autoimmune disease that is caused by mutations in the AIRE gene. Murine studies have linked AIRE to thymocyte selection and peripheral deletional tolerance, but the pathogenesis of the human disease remains unclear. In this study, we show that APECED patients have elevated IL-7 levels and a drastically decreased expression of IL-7R on CD8+ T cells. This is associated with increased proliferation and a decreased expression of the negative TCR regulator CD5 in the CD45RO− subset. The CD45RO− cells also display oligoclonal expansions, decreased expression of the lymph node homing factors CCR7 and CD62L, and increased expression of perforin, consistent with the accumulation of highly differentiated effector cells. The CD45RO−CCR7+CD8+ population of cells with markers characteristic of naive phenotype is also skewed, as shown by decreased expression of CD5 and increased expression of perforin. The putative CD31+ recent thymic emigrant population is likewise affected. These data are consistent with IL-7 dysregulation inducing a decreased threshold of TCR signaling and self-antigen–driven proliferation, probably in synergy with the failed thymic selection. The resultant loss of CD8+ T cell homeostasis is likely to play a significant role in the pathogenesis of APECED. Our findings may also hold lessons for other diseases in which the IL-7–IL-7R pathway has emerged as a risk factor.

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supporting

confidence: 63%

IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy

Laakso

Kekäläinen

Rossi

et al. 2011

The Journal of Immunology

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“…Recently, we have studied Th17 responses in APECED patients in vivo and found a predominant defect in IL-22 production both in antigenchallenged skin and unexposed skin [18]. Similarly, the composition of the CD4 + population has been reported to be either normal or skewed, and the full pattern of functional Th differentiation has not been studied [17,19,20]. Here, we report the characteristics of the circulating Th cell population in Finnish APECED patients.…”

Section: Introductionmentioning

confidence: 93%

“…The transcriptome of patient and control lymphocytes was determined adapting the previously described single-cell reverse transcription method for 5′-end RNAseq [20] and upscaling the reaction volumes for microtiter plates. Total bulk RNA was extracted from about 4 × 10 5 cells with RNeasy kit (Qiagen) and diluted to 4 ng/μL concentration.…”

Section: Transcriptome Analysismentioning

confidence: 99%

“…Sequencing was performed on an Illumina HiSeq 2000 instrument generating 50-bp reads, including a 6-bp unique molecular identifier along with 8-bp index reads corresponding to the cell-specific barcode. Components of the library reaction mixes have been described earlier [20,21], and details of the modified protocol are available on request. Sequence reads were filtered and trimmed as described earlier [20,21] and aligned to the human UCSC reference genome.…”

Section: Transcriptome Analysismentioning

confidence: 99%

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Expanded CD4+ Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma

et al. 2016

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“…Such abnormalities remain variable from one patient to another and depend on the context (recent infection, age). However they have previously been reported in a few patients [36,37]. Several hypotheses could be suggested.…”

Section: Discussionmentioning

confidence: 96%

Autoimmune Polyendocrine Syndrome Type 1 in North-Western France: <i>AIRE</i> Gene Mutation Specificities and Severe Forms Needing Immunosuppressive Therapies

et al. 2010

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Background: Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations. Methods: Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing. Results: Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1–10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967–979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected. Conclusion: APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.

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Immunophenotypic Characterisation of Peripheral Blood Lymphocytes in Autoimmune Polyglandular Syndrome Type 1: Clinical Study and Review of the Literature

Cited by 27 publications

References 32 publications

IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy

IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy

Expanded CD4+ Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma

Autoimmune Polyendocrine Syndrome Type 1 in North-Western France: <i>AIRE</i> Gene Mutation Specificities and Severe Forms Needing Immunosuppressive Therapies

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