Endocrine Abstracts

Background: Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome is an autosomal recessive disorder due mutations in SLC29A3. SLC29A3 encodes for an equilibrative nucleoside transporter 3 (ENT 3). A hallmark of PHID syndrome is the chronic inflammation characterised by the persistently raised erythrocyte sedimentation rate and C-reactive protein. A key pathway involved in triggering inflammation is the nuclear factor kappa β (NF-kB) pathway. NF-kB is a transcription factor which when activated will trigger a host of genes involved in regulating the inflammatory response. Thus activation and modulation NF-kB pathway is central to the inflammatory pathway. The mechanism/s underlying the chronic inflammatory response in patients with PHID is/are not known.

Aims: To understand the molecular basis of the inflammatory response in PHID syndrome.

Methods: Serum amyloid A protein levels were measured patients with PHID syndrome. The expression of SLC29A3 was knocked down in HeLa cells using SLC29A3 specific shRNA constructs in GIP Lentiviral plasmids (Open Biosystems, Huntsville USA) and the inflammatory response to SLC29A3 knockdown was interrogated using a construct with tandem NF-kB response elements driving Luciferase (pGL4.32[luc2P/NF-κB-RE] Promega).

Results: Serum amyloid A protein levels were markedly elevated (60–90 mg/dl ref <10). Our preliminary data indicate that knock-down of SLC29A3 expression alters the inflammatory response mediated by NF-kB response.

Conclusion: The inflammatory response in PHID patients is associated with the accumulation of serum amyloid A protein and our preliminary data indicate that the transcription factor NF-kB may be involved in the inflammatory cascade. Further studies are required to understand the link between nucleoside transport and the inflammatory response in patients with PHID syndrome.