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Sökning: WFRF:(Thienemann F)

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  • Kalinowski, A., et al. (författare)
  • Evaluation of C4 gene copy number in Pediatric Acute Neuropsychiatric Syndrome
  • 2023
  • Ingår i: Developmental Neuroscience. - 0378-5866. ; 45:6, s. 315-324
  • Tidskriftsartikel (refereegranskat)abstract
    • Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of co-morbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically-matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) was used to assess whether the time to Juvenile Idiopathic Arthritis (JIA) or Autoimmune Disease (AI) onset was a function of total C4A or C4B. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (Hazard Ratio = 2 7, p-value = 0 004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.
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