Publications by authors named "K Siepermann"
Article Synopsis
- * Variants of UNC93B1 (E92G and R336L) were found in patients with early-onset systemic lupus erythematosus (SLE), correlating with heightened inflammatory responses when stimulated by TLR7/TLR8 agonists.
- * The E92G variant destabilizes the UNC93B1 protein, leading to increased TLR7 activity and type I interferon signaling, pointing to a potential therapeutic target for managing SLE by focusing on TLR7.
Most of the currently known heterozygous pathogenic (Nuclear factor kappa B subunit 1) variants comprise deleterious defects such as severe truncations, internal deletions, and frameshift variants. Collectively, these represent the most frequent monogenic cause of common variable immunodeficiency (CVID) identified so far. encodes the transcription factor precursor p105 which undergoes limited proteasomal processing of its C-terminal half to generate the mature NF-κB subunit p50.
View Article and Find Full Text PDFAMPK (adenosine monophosphate-activated protein kinase) is phosphorylated (AMPK-P) in response to low energy through allosteric activation by Adenosine mono- or diphosphate (AMP/ADP). Folliculin (FLCN) and the FLCN-interacting proteins 1 and 2 (FNIP1, 2) modulate AMPK. FNIP1 deficiency patients have a AMPK-P gain of function phenotype with hypertrophic cardiomyopathy, Wolff-Parkinson-White pre-excitation syndrome, myopathy of skeletal muscles and combined immunodeficiency.
View Article and Find Full Text PDFArticle Synopsis
- Autoimmune lymphoproliferative syndrome (ALPS) results from defective Fas signaling, leading to the accumulation of abnormal double-negative T (DNT) cells that have a unique memory-like state and significant proliferative potential.
- ALPS DNT cells show high levels of activation and proliferation, connected to hyperactive signaling through serine-threonine kinases like Akt and mTOR, which are critical for their survival.
- Inhibiting mTOR with rapamycin effectively reduces the proliferation of DNT cells both in vitro and in vivo, highlighting mTOR's role as a key player in regulating lymphoproliferation and abnormal T cell differentiation in ALPS.