Journal of internal medicine
-
Review
Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I.
Autoimmune polyendocrine syndrome type I (APS-I) is a monogenic model disease of autoimmunity. Its hallmarks are chronic mucocutaneous candidosis, hypoparathyroidism and adrenal insufficiency, but many other autoimmune disease components occur less frequently. The first components usually appear in childhood, but may be delayed to adolescence or early adult life. ⋯ Antibodies against interferon-omega and -alpha have recently been shown to be sensitive and relatively specific markers for APS-I, and mutational analysis of the autoimmune regulator gene gives the diagnosis in >95% of cases. The treatment and follow-up of patients is demanding and requires the collaboration of specialists of several fields. However, the literature is especially sparse regarding information on treatment and follow-up; hence, we present here a comprehensive overview on clinical characteristics, treatment and follow-up based on personal experience and published studies.
-
Autoimmune polyendocrine syndromes type 1 and 2 (APS-1 and APS-2) are diverse in regards to their component diseases and immunologic features of pathogenesis. Animal models and human studies highlight the importance of alleles of HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Knowledge of the syndromes and component diseases allows clinicians to recognize and prevent illness prior to morbidity. ⋯ Once genetically susceptible individuals are identified screening for autoantibodies can be performed. Amongst autoantibody positive individuals, monitoring for physiologic decompensation, with a goal of treating prior to morbidity and in some cases mortality, follows. With continued basic and clinical research, therapies aimed at treating the underlying autoimmunity and disease prevention should become possible.
-
QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample. ⋯ We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, gender- and heart rate-adjusted QT interval and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.
-
To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). ⋯ These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.