TY - JOUR
T1 - Immunological findings in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and their family members
T2 - Are heterozygotes subclinically affected?
AU - Šedivá, Anna
AU - Čihǎkovǎ, Daniela
AU - Lebl, Jan
N1 - Funding Information:
This study was supported by Complex Research Programs 111300001 and 111200001 from the Ministry of Education and 00000064203 from Ministry of Health of the Czech Republic.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED; APS-1) is an autosomal recessive autoimmune disease, caused by mutations in the AIRE (autoimmune regulator) gene. Due to the proposed role of AIRE in central immune tolerance, the immune investigation of four females diagnosed with APECED, their siblings, parents and 14 age-matched controls was performed. The parameters analyzed included immunoglobulins, autoantibodies, cellular immunity and production of cytokines IFNγ, IL-4 and IL-10, reflecting Th1xTh2 balance. Low IFNγ levels (455 ± 191 pg/ml) were detected in all affected girls compared to controls (910 ± 406 pg/ml). Two girls with homozygous R257X mutations showed similarly marked elevation of IgM and increase of CD3+CD4+ lymphocytes. Positive autoantibodies against smooth muscle were found in one affected girl; another girl and her mother had antibodies against gastric parietal cells. Interestingly, all fathers had dramatically elevated levels of IgA and activated T lymphocytes. High frequency of abnormal immune results among parents is a novel finding which might suggest a subclinical immune deficit in heterozygotes with AIRE mutations.
AB - Autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED; APS-1) is an autosomal recessive autoimmune disease, caused by mutations in the AIRE (autoimmune regulator) gene. Due to the proposed role of AIRE in central immune tolerance, the immune investigation of four females diagnosed with APECED, their siblings, parents and 14 age-matched controls was performed. The parameters analyzed included immunoglobulins, autoantibodies, cellular immunity and production of cytokines IFNγ, IL-4 and IL-10, reflecting Th1xTh2 balance. Low IFNγ levels (455 ± 191 pg/ml) were detected in all affected girls compared to controls (910 ± 406 pg/ml). Two girls with homozygous R257X mutations showed similarly marked elevation of IgM and increase of CD3+CD4+ lymphocytes. Positive autoantibodies against smooth muscle were found in one affected girl; another girl and her mother had antibodies against gastric parietal cells. Interestingly, all fathers had dramatically elevated levels of IgA and activated T lymphocytes. High frequency of abnormal immune results among parents is a novel finding which might suggest a subclinical immune deficit in heterozygotes with AIRE mutations.
KW - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
KW - Autoimmunity
KW - Immune tolerance
KW - Interferon gamma
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U2 - 10.1515/JPEM.2002.15.9.1491
DO - 10.1515/JPEM.2002.15.9.1491
M3 - Article
C2 - 12503856
AN - SCOPUS:0036914217
VL - 15
SP - 1491
EP - 1496
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
SN - 0334-018X
IS - 9
ER -