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

Abstract

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.

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

“…HP is the most common autoimmune component, with a prevalence that ranges from 77 to 96 % [7,19,23,[84][85][86]. A lower prevalence of 63 % was found among 19 French patients [87]. Isolated primary HP is extremely rare, and therefore APECED diagnosis should be considered in any patient with this endocrinopathy.…”

“…The prevalence of AD is reportedly between 63 and 92 %, making it the second most common endocrine disorder [7,19,23,[84][85][86][87]. AD is thought to be mediated by autoreactive cytotoxic T-cells [89][90][91], but the adrenal hormone deficiencies do not manifest clinically until at least 90 % of the functional adrenocortical cells have been destroyed [92,93].…”

Recalcitrant Hypocalcaemia in Autoimmune Enteropathy

“…8 Small case series have shown improvement with immunosuppression. 2,22,25 The swift and persistent improvement in enteropathy in this case highlights the need for consideration of early commencement of immunosuppression and further studies balancing their risks with regression of the aspects of the disease.…”

“…Other immunosuppressive agents have been used successfully such as pulse methylprednisolone, cyclophosphamide, and azathioprine, with smaller studies involving mycophenolate, 6-mercaptopurine, tacrolimus, sirolimus, infliximab, and rituximab. [23][24][25] CONCLUSIONS Primary hypoparathyroidism in children is a rare presentation, and consideration of APECED should be made, particularly if associated with family history of autoimmunity. 1,4,5 This instructive case highlights multiple factors involved in calcium absorption including calcium formulation, gastric acidity, enteroendocrine cells, and glucocorticoids.…”

Genetic disorders with immune dysregulation

“…Immunosuppression has not been routinely utilized in APECED patients although there has been reported benefit of various combinations of cyclosporine, tacrolimus, methotrexate, azathioprine, and steroids for severe autoimmune renal, hepatic, and bowel disease [18,19]. The development of pathogenic autoantibodies in many cases suggests that B cell depletion therapy (i.e.…”