T CHEN1, 2, Q CAO1, 2, R WANG1, P RAO1, 2, G ZHENG1, 2, Y WANG1, 2, DC HARRIS1, 2

1The Westmead Institute for Medical Research, Westmead, NSW; 2University of Sydney, Camperdown, NSW

Aim: To investigate the correlation between CD141+ dendritic cell (DC) infiltration and clinicopathologic features in IgA nephropathy.

Background: Previous studies have shown that the severity of interstitial inflammatory infiltrates, which include myeloid DCs, correlates with progression of IgA nephropathy. CD141+ DCs have recently been identified as a unique myeloid DC subset that plays a significant role in the induction and regulation of immunity. This DC subset has been studied in mouse models, but studies in humans are lacking.

Methods: Thirty adult patients with a sole diagnosis of IgA nephropathy were included in this study. Patients were excluded if they had received glucocorticoids or immunosuppressant therapy before renal biopsy. The histological classification was scored according to the Oxford classification. CD141+ DCs were identified through immunofluorescence staining and visualised using confocal microscopy.

Results: In normal human kidney, CD141+DC were rarely present. Patients with IgA nephropathy had significantly higher number of CD141+ DCs than normal control (P=0.021) and CD141+DCs were mainly present in the interstitium. Higher CD141+ DC density was significantly associated with worse serum creatinine (r=0.81, P=0.015) and proteinuria (r=0.75, P=0.049). Higher CD141+ DC density was also associated with increased severity of tubular atrophy/interstitial fibrosis (P=0.025), but not with mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis or number of crescents.

Conclusions: Our data highlight the close correlation between the density of CD141+ DCs and clinicopathologic features of IgA nephropathy progression. Further studies will be conducted in human samples and murine models to investigate whether CD141+ DCs mediate kidney injury, and the possible mechanisms involved.

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