ESPN 53rd Annual Meeting

ESPN 2021


 
SOLUBLE CD89 IS A CRITICAL FACTOR FOR MESANGIAL PROLIFERATION IN CHILDHOOD IgA NEPHROPATHY.
ALEXANDRA CAMBIER 1 PATRICK JAMES GLEESON 2 LILIA ABBAD 2 FANNY CANESI 2 JENNIFER DA SILVA 2 JULIE BEX-COUDRAT 2 GEORGES DESCHENES 3 OLIVIA BOYER 4 MARION RABANT 4 TIM ULINSKI 5 MICHEL PEUCHMAUR 3 LAURELINE BERTHELOT 2 RENATO MONTEIRO 2

1- SAINTE JUSTINE HOSPITAL
2- CENTRE DE RECHERCHE SUR LINFLAMMATION (CRI); INSERM U1149
3- HôPITAL ROBERT DEBRé
4- HôPITAL NECKER
5- HôPITAL TROUSSEAU
 
Introduction:

 Childhood IgA nephropathy (cIgAN) includes a wide spectrum of clinical presentations, from isolated hematuria to acute nephritis with rapid loss of renal function. IgAN is an autoimmune disease and its pathogenesis involves galactose deficient (Gd) IgA1, IgG anti-Gd-IgA1 autoantibodies and the soluble IgA Fc receptor (sCD89). However, the implications of such factors in cIgAN pathogenesis remain unclear.

Material and methods:

 Here, we studied these biomarkers in a cohort of 67 cIgAN patients and 42 controls but also in vivo with human mesangial cells and in vivo with human IgA transgenic mice.

Results:

 While Gd-IgA1 was only moderately enhanced in patient plasma, levels of circulating IgA complexes (sCD89-IgA and IgG-IgA) and free sCD89 were markedly increased in cIgAN. sCD89-IgA1 complexes and free sCD89 correlate with proteinuria, as well as histological markers of disease activity: mesangial, endocapillary hypercellularity and cellular crescent. Mesangial sCD89 deposits were detected in cIgAN biopsies. Plasma chromatography fractions containing sCD89-IgA1 or free sCD89 from patients induced mesangial cell proliferation in vitro. Recombinant (r) sCD89 induced mesangial cell proliferation in vitro that was inhibited by rCD71 or rapamycin. Injection of rsCD89 induced marked glomerular proliferation and proteinuria in human IgA1 transgenic mice. 

Conclusions:

 In conclusion, free and IgA1-complexed sCD89 are key players in mesangial proliferation. These findings reveal a new role for sCD89 in cIgAN, making it a potentially useful biomarker and therapeutic target.