ArticleThe Journal of clinical endocrinology and metabolism2024
PAPP-A as a Potential Target in Thyroid Eye Disease.
Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A bispecific-aptamer TSHR-CD80-1 treats thyroid eye disease by inhibiting CD8Cell communication and signaling : CCS · 2026Article
- Tryptophan metabolites exert potential therapeutic activity in graves' orbitopathy by ameliorating orbital fibroblasts inflammation and proliferation.Journal of endocrinological investigation · 2025Article
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Authors and funding
3 authors.
Funding
Abstract
contextProptosis in thyroid eye disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects.
objectiveTo test the hypothesis that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitors attenuates IGF-IR signaling in TED. Informed consent was obtained from patients with TED undergoing surgery, and retro-orbital tissue was collected for fibroblast isolation and culture. Operations were performed in Mayo Clinic operating suites. Cell culture was performed in a sterile tissue culture facility. Retro-orbital tissue was collected from 19 patients with TED.
methodsTreatment of TED fibroblasts with proinflammatory cytokines. Flow separation of CD34- and CD34+ orbital fibroblasts, the latter representing infiltrating fibrocytes into the orbit in TED. PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway, and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status, and associated PAPP-A and IGF-IR expression were measured.
resultsProinflammatory cytokines markedly increased PAPP-A expression in TED fibroblasts. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A's proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from patients with TED. TED fibroblasts that were CD34+ represented ∼80% of the cells in culture and accounted for ∼70% of PAPP-A and IGF-IR-expressing cells.
conclusionThese results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis.
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