Glomerulonephritis after hematopoietic cell transplantation: IgA nephropathy with increased excretion of galactose-deficient IgA1

Abstract

We report the development of IgA nephropathy (IgAN) following full myeloablative allogeneic hematopoietic cell transplantation in two patients with human leukocyte antigen (HLA) matched sibling donors, unrelated to active or chronic graft-versus-host disease. Both recipients had elevated urinary levels of galactose-deficient IgA1, and one donor-recipient pair had elevated serum levels of galactose-deficient IgA1. We propose that IgAN developed after bone marrow transplantation due to a non-graft-versus-host-disease-related multi-hit process associated with glomerular deposition of galactose-deficient IgA1. These two cases provide unique insight into the kinetics of overproduction of galactose-deficient IgA1 and its glomerular deposition and consequential renal injury in IgAN.

Fig. 1

Chimerism study for patient 1: DNA typing by polymerase chain reaction technique was used to detect differences in allele types between the donor and recipient cells at several short tandem repeat loci of the bone marrow (BRT Laboratories, Inc, Baltimore, MD). Only donor types were detected as shown (black arrows) in the comparison of lane 15 (the donor sample for patient 1) and lane 16 (the post-transplant bone marrow sample of patient 1) in 2003.

Fig. 2

Chimerism study for patient 2: normal female chromosome complement was observed in all metaphases, without evidence for acquired clonal abnormality, by cytogenetic karyotyping of post-transplant bone marrow aspirate in 2008. The 46, XX karyotype (black arrow) is consistent with engraftment by female donor cells (Quest Diagnostics Nichols Institute, Chantilly, VA).

Fig. 3

A) Light microscopy (patient 1)—a large cellular crescent with a long strand of fibrin is seen in the urinary space of this glomerulus (black arrow). The capillary tuft appears compressed and reveals mild mesangial hypercellularity (H&E, ×250). B) Light microscopy (patient 2)—glomerulus showing segmental focus of necrosis with fibrin extravasation in the capillary lumina (black arrows) and Bowman's space and epithelial cell proliferation. Note the mild increase of mesangial cellularity. The capillaries are patent and the glomerular basement membrane is unremarkable (H&E, ×400). C) Immunofluorescence (patient 1)—glomerulus stained with IgA antiserum showing abundant mesangial deposits of 3+ intensity (fluorescein isothiocyanate stained section ×400). D) Electron microscopy (patient 1)—glomerulus showing large mesangial electron-dense deposits (white arrows). The mesangial cells appear active (original magnification ×16 000).