ESPN 54th Annual Meeting

ESPN 2022


 
X-linked hypophosphatemia: not only a phosphate/calcium disorder but also an inflammatory disease
MEAUX MARIE-NOELLE 1 ALIOLI CANDIDE 2 LINGLART AGNES 3 LEMOINE SANDRINE 4 VIGNOT EMMANUELLE 4 BERTHOLET-THOMAS AURéLIA 4 PEYRUCHAUD OLIVIER 4 FLAMMIER SACHA 4 MACHUCA-GAYET IRMA 4 BACCHETTA JUSTINE 1

1- Centre de Référence des Maladies Rares du Calcium et du Phosphore, Centre de Référence des Maladies Rénales Rares Filières Maladies Rares ORKID, OSCAR et ERN ERK-Net et BOND, CHU de Lyon, Bron, France
2- INSERM, UMR 1033, FACULTé DE MéDECINE LYON EST, UNIVERSITé CLAUDE BERNARD LYON 1, LYON, FRANCE
3- PARIS
4- LYON
 
Introduction:

X-linked hypophosphatemia (XLH) is a rare genetic disease caused by a primary excess of FGF23. Treatment consists either in Standard of care (SOC) using phosphore plus active vitamin D, either in biotherapy: burosumab. FGF23 has been associated with inflammation and impaired osteoclastogenesis, however these pathways have not yet been studied in XLH. The aim of our study was to evaluate whether XLH patients display peculiar inflammatory and osteoclastic profile.

Material and methods:

We performed a prospective multicenter cross-sectional study analyzing transcript expression of 8 inflammatory markers (Il6, Il8, Il1β, CXCL1, CCL2, CXCR3, Il1R, Il6R) by RT-qPCR on PBMCs (peripheral blood mononuclear cells) extracted from total blood samples from 28 XLH patients (17 children, 11 burosumab) and 19 healthy controls. We also differentiated PBMCs into mature osteoclasts using RANKL/MCSF in the presence/absence of native/active vitamin D, osteoclasts were TRAP-stained and counted at the end of the differentiation process.

Results:

Expression of all inflammatory markers (except Il6R) were significantly increased in PBMCs from XLH patients as compared to controls. No differences were observed between the two sub-groups of patients, namely SOC and burosumab. Osteoclastogenesis was significantly impaired in XLH patients as compared to controls, and osteoclasts derived from XLH patients also expressed more inflammatory markers. The pro-inflammatory-like profile at the end of the osteoclastic differentiation process decreased in cells derived from patients receiving burosumab. Burosumab treatment restored the capacity of PBMCs-derived osteoclasts to respond to native vitamin D. The adjunction of active vitamin D in culture during the osteoclastic differentiation decreased the expression of inflammation markers.

Conclusions:

We describe for the first time a pro-inflammatory-like profile in XLH. XLH patients have a propensity to develop arterial hypertension and obesity, and since inflammation can worsen these clinical outcomes, we hypothesize that inflammation might play a crucial role in extra-skeletal complications of XLH.