Gastrointestinal immunity against tryptophan hydroxylase-1, aromatic L-amino-acid decarboxylase, AIE-75, villin and Paneth cells in APECED

Kluger, Nicolas; Jokinen, Martta; Lintulahti, Anu; Krohn, Kai; Ranki, Annamari

doi:10.1016/j.clim.2015.03.012

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…Eighty-one APS1/APECED patients were diagnosed by mutational analysis of AIRE and by autoantibodies to type I IFNs. All provided informed consent, and many were analyzed previously ( Kisand et al., 2011 , Kluger et al., 2015 , Meloni et al., 2012 , Wolff et al., 2007 ). Approvals by local ethics committees are described in the Supplemental Experimental Procedures .…”

Section: Methodsmentioning

confidence: 99%

AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies

Meyer¹,

Woodward

Hertel³

et al. 2016

Cell

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244

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SummaryAPS1/APECED patients are defined by defects in the autoimmune regulator (AIRE) that mediates central T cell tolerance to many self-antigens. AIRE deficiency also affects B cell tolerance, but this is incompletely understood. Here we show that most APS1/APECED patients displayed B cell autoreactivity toward unique sets of approximately 100 self-proteins. Thereby, autoantibodies from 81 patients collectively detected many thousands of human proteins. The loss of B cell tolerance seemingly occurred during antibody affinity maturation, an obligatorily T cell-dependent step. Consistent with this, many APS1/APECED patients harbored extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines. Such antibodies were biologically active in vitro and in vivo, and those neutralizing type I interferons (IFNs) showed a striking inverse correlation with type I diabetes, not shown by other anti-cytokine antibodies. Thus, naturally occurring human autoantibodies may actively limit disease and be of therapeutic utility.

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Section: Methodsmentioning

confidence: 99%

AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies

Meyer¹,

Woodward

Hertel³

et al. 2016

Cell

Self Cite

244

272

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“…Data could also be retrieved by the analysis of the Finnish series published by Merenmies and Tarkkanen et al [50] where, based on the appearance of chronic bilateral keratitis, 9/17 patients (52.9%) could have had an earlier diagnosis of APECED. Thus, it is important to remember the high incidence of some non-endocrine manifestations such as intestinal dysfunction and ectodermal dystrophies [24,50,51]. Clearly, as stated above, our analysis on the Turkish series is limited by its retrospective nature since data are derived from the available scientific literature on APECED.…”

Section: Discussionmentioning

confidence: 99%

“…American APECED patients showed a diverse clinical picture, with dramatic enrichment of organspecific non-endocrine manifestations starting early in life, compared to European cohorts [9]. In this regard, even in highest European prevalence cohort, the Finns, APECED patients show an increasing and higher recurrence of non-endocrine inflammatory manifestations, in particular autoimmune gastrointestinal dysfunction [24]. Interestingly, autosomal dominant AIRE mutations in the first plant homeodomain (PHD1) zinc finger are associated with organ-specific autoimmune conditions [25].…”

Section: Introductionmentioning

confidence: 97%

APECED in Turkey: A case report and insights on genetic and phenotypic variability

Fierabracci

Pellegrino

Frasca

et al. 2018

Clinical Immunology

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APECED is a rare monogenic recessive disorder caused by mutations in the AIRE gene. In this manuscript, we report a male Turkish patient with APECED syndrome who presented with chronic mucocutaneous candidiasis associated with other autoimmune manifestations developed over the years. The presence of the homozygous R257X mutation of the AIRE gene confirmed the diagnosis of APECED syndrome. We further performed literature review in 23 published Turkish APECED patients and noted that Finnish major mutation R257X is common in Turks. In particular, we assessed retrospectively how often the Ferre/Lionakis criteria would have resulted in earlier diagnosis in Finns, Sardinians and Turks in respect to the classic criteria. Since an earlier diagnosis could have been possible in 18.8% of Turkish, in 23.8% of Sardinian and 38.55% of Finnish patients we reviewed from literature, Ferre/Lionakis criteria could indeed allow in future earlier initiation of immunomodulatory treatments, if found effective in future studies.

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“…Eine Ausnahme ist die juvenile Form des PGAS, bei welchem ein isolierter Verlust bzw. eine Rarefizierung endokriner Zellen in der Schleimhaut gefunden werden kann [5,11,24].…”

Section: Histologische Veränderungen Bei Pgasunclassified

Polyglanduläre autoimmune Syndrome

Komminoth

2016

Pathologe

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Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

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Gastrointestinal immunity against tryptophan hydroxylase-1, aromatic L-amino-acid decarboxylase, AIE-75, villin and Paneth cells in APECED

Cited by 20 publications

References 32 publications

AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies

AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies

APECED in Turkey: A case report and insights on genetic and phenotypic variability

Polyglanduläre autoimmune Syndrome

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