Collagen α5 and α2(IV) chain coexpression: Analysis of skin biopsies of Alport patients

Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5 gene with the X-linked form being most prevalent. The resultant α5(IV) collagen chain is a component of the glomerular and skin basement membranes (SBMs). Immunofluorescent determination of the α5(IV) chain in skin biopsies is the procedure of choice to identify patients. In 30% of patients, however, the mutant protein is still found in the SBM resulting in a normal staining pattern. In order to minimize or eliminate false results, we compared the distribution of the α2(IV) chain (another SBM component) and the α5(IV) chain by standard double label immunofluorescence (IF) and by confocal laser scanning microcopy. The study was performed on 55 skin biopsies of patients suspected of Alports and five normal control specimens. In normal skin, IF showed the classical linear pattern for both collagens along the basement membrane. Additionally, decreased α5(IV) was found in the bottom of the dermal papillary basement membrane. Confocal analysis confirmed the results and show α5(IV) focal interruptions. In suspected patients, both techniques showed the same rate of abnormal α5(IV) expression: segmental in women and absent in men. Our results show a physiological variation of α5(IV) location with focal interruptions and decreased expression in the bottom of the dermal basement membrane. Comparison of α5(IV) with α2(IV) expression is simple and eliminates technical artifacts

Post-allogeneic haematopoietic stem cell transplantation membranous nephropathy: clinical presentation, outcome and pathogenic aspects

BACKGROUND: Post-allogeneic haematopoietic stem cell transplantation (HSCT) membranous nephropathy (MN), a rare complication of HSCT, remains an ill-defined entity. We describe the clinical and biological characteristics and outcome of five patients with post-HSCT MN, review the previously reported cases and discuss the pathogenic aspects of this nephropathy. METHODS: Cases were identified by using a questionnaire sent to nephrologists and pathologists in French university and general hospitals. Medical records and kidney biopsy specimens were reviewed and relevant data were collected. Moreover, the IgG subclasses in glomerular deposits and the presence of chimeric renal cells were studied. RESULTS: Five patients were identified. All had a history of chronic graft-vs-host disease (cGVHD) and all had active manifestations of cGVHD at MN diagnosis. Mean time between HSCT and diagnosis of MN was 24.4 months. Renal insufficiency was present in four patients. Renal biopsy examination showed typical features of MN in all patients. IgG1 and IgG4 were the predominant IgG subclasses in the glomerular deposits. No chimeric glomerular cell was detected. Initial treatment for MN consisted in corticosteroids and immunosuppressors (ciclosporin, mycophenolate mofetil, rituximab, chlorambucil) in all patients. Complete remission of nephrotic syndrome (NS) occurred in two patients, partial remission in one patient, while treatment was inefficacious in one (data not available for one patient). Most interestingly, the evolution of NS paralleled the evolution of cGVHD in all patients. CONCLUSION: Our data suggest an association between cGVHD and post-HSCT MN. Treatment, mainly steroids and ciclosporin, should be aimed at the control of acute manifestations of cGVHD