ABSTRACT.
IgA nephropathy (
IgA-N) that comprises
Berger disease and Henoch-Schönlein
Purpura (HSP)
nephritis is defined by mesangial
IgA deposits. Recently, this group has characterized a new receptor for
IgA, the
transferrin receptor (CD71), expressed on mesangial cells. To assess whether CD71 was involved in the pathogenesis of
IgA-N, its expression was analyzed together with
IgA deposits on 16 kidney biopsies from 16 patients with
Berger disease (n = 4) or HSP (n = 12). These biopsies were compared with 17 kidney biopsies of a group of 15 patients (control group) with other
glomerulonephritis, including
systemic lupus erythematosus, poststreptococcal acute
glomerulonephritis, membranoproliferative glomerulonephritis,
steroid-sensitive
minimal change nephrotic syndrome,
steroid-resistant idiopathic nephrotic syndrome with focal and
segmental glomerulosclerosis, and persistent and isolated
proteinuria with minimal change on kidney biopsy. In this control group,
IgA deposits could be observed in eight kidney biopsies of seven patients. These biopsies were also compared with normal kidney specimens (normal group). In normal kidney, it was found that CD71 was linearly expressed on tubular epithelium but was either not expressed or very dimly in glomeruli. In contrast, CD71 was strongly expressed in 105 of the 107 glomeruli of the kidney biopsies from the
IgA-N group. For the control group, it was found that expression of CD71 in glomeruli was correlated to the presence of
IgA deposits. Indeed, among the 87 glomeruli of nine kidney biopsies (eight patients) without
IgA fixation, 78 exhibited no CD71 expression and nine exhibited a very dim one. On the other hand, all 49 glomeruli of the eight kidney biopsies (seven patients) in which
IgA deposits were detected exhibited CD71 expression (P < 10(-4)). Performance of dual-labeling studies with confocal microscopy on kidney biopsies of
IgA-N patients demonstrated that most of the
IgA deposits co-localized with CD71. It was also demonstrated that the intensity of the expression of CD71 was not linked to the intensity of clinical or
biologic findings but to the intensity of cellular proliferation in both
IgA-N and control groups. These results show that mesangial CD71 expression is not specific to
IgA-N. However, the association between
IgA deposits and CD71 expression and their co-localization in the mesangium provide strong evidence that CD71 is a major
IgA receptor on mesangial cells.