IgA nephropathy and Henoch???Sch??nlein purpura nephritis

Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee, USA.
Current Opinion in Pediatrics (Impact Factor: 2.53). 05/2008; 20(2):163-70. DOI: 10.1097/MOP.0b013e3282f4308b
Source: PubMed


IgA nephropathy and Henoch-Schönlein purpura nephritis are common glomerular disorders in pediatrics that can potentially progress to end-stage renal disease in some patients. This review summarizes our current understanding of the pathogenesis of these closely related conditions and discusses the rationale for development of diagnostic tests and prognostic markers. The review also presents the best data for long-term outcome, clinical markers of prognosis, and the results of randomized controlled trials.
Our understanding of the defective galactosylation of O-linked glycans in the hinge region of human IgA1 and its role in the pathogenesis of IgA nephropathy and Henoch-Schönlein purpura nephritis has evolved over the past decade. This review discusses studies that suggest that demonstration of galactose-deficient IgA1 in the serum may become an important diagnostic tool for these conditions. Proteomic techniques for development of biomarkers for diagnosis and prognosis show promise. Although data from randomized controlled trials have failed to support the use of immunosuppressive agents in pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis, recent data indicate that angiotensin converting enzyme inhibitor therapy is indicated for reduction of proteinuria.
Childhood IgA nephropathy and Henoch-Schönlein purpura nephritis have the potential for serious morbidity, either during childhood or later in adulthood. In the future clinical tests will be used for noninvasive diagnosis and as markers for judging response to treatment, particularly in those individuals at highest risk for eventual progression to end-stage renal disease.

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    • "The hallmarks of activation of mesangial as well as tubular cells are de novo expression of α-smooth muscle actin (α-SMA) and overproduction of the interstitial matrix components [12]. Additionally, it was suggested that during inflammation monocytes/macrofages may produce MMP-2 and MMP-9 [6]. Therefore, the aim of the present study was to determine glomerular immunoexpression of MMP-2 and MMP-9 in IgAN and SHN. "
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    ABSTRACT: Both idiopathic IgA nephropathy (IgAN) and Schoenlein-Henoch nephritis (SHN) are characterized by cell proliferation and abnormal extracellular matrix (ECM) remodeling by mesangial cells leading to fibrosis, sclerosis and end-stage renal disease. Matrix metalloproteinases MMP-2 and MMP-9 are reported as the most important proteolytic enzymes involved in remodeling of ECM. Therefore, the aim of the present study was to determine glomerular immunoexpression of MMP-2 and MMP-9 in IgAN and SHN. Another purpose of this study was to examine the relationship between expression of MMPs and mesangial cells, a-smooth muscle actin (alpha-SMA) staining, and monocytes/macrophages. Fifteen patients with idiopathic IgAN and 12 with SHN were examined by percutaneous renal biopsy. Glomerular staining intensity of MMP-2 and MMP-9 was recorded semiquantitatively, whereas mesangial cells, glomerular alpha-SMA staining and glomerular CD 68+ cells were assessed quantitatively using computer image analysis system. Our study revealed that the mean values of glomerular immunoexpression of MMP-2, mesangial cells, alpha-SMA staining and glomerular CD 68+ cells were in SHN patients significantly increased as compared to IgAN cases whereas glomerular staining for MMP-9 did not differ in these groups. Moreover, a glomerular staining of MMP-2 was significantly positively correlated with mesangial cells as well as glomerular alpha-SMA staining in both SHN and IgAN. A positive significant correlation between glomerular MMP-2 staining and glomerular CD68+ cells was noted only in SHN group. The correlations of glomerular MMP-9 and these parameters were weak and not significant. In conclusion, our results confirm increased glomerular staining of MMP-2 but not MMP-9 in SHN patients. A suggestion that augmented mesangial cells proliferation in these cases depends on MMP-2, alpha-SMA and monocytes/macrophages needs further investigations including double staining study.
    Folia Histochemica et Cytobiologica 06/2010; 48(1):63-7. DOI:10.2478/v10042-008-0086-4 · 1.36 Impact Factor
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    • "Four cases of IgA MM presenting as HSP have been reported since 1980 (van der Helm-Van Mil et al, 2003), and in two cases a pattern of altered O-linked glycosylation in the hinge region between CH1 and CH2 regions of the IgA heavy chain has been identified by mass spectrometry (van der Helm-Van Mil et al, 2003), which is similar to findings in HSP patients in whom the pathophysiology is thought to be autoantibody formation against the galactose deficient IgA and subsequent complement activation and vascular injury (Sanders & Wyatt, 2008). Successful treatment of IgA MM led to resolution of all signs and symptoms of HSP (Zickerman et al, 2000; Sanders & Wyatt, 2008). "
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    ABSTRACT: Unexpectedly high rates of venous thromboembolic events (VTE) concurrent with the introduction of highly effective immune modulating drugs thalidomide and lenolidomide for treatment of multiple myeloma have focused attention on the incidence and underlying pathophysiology of VTE in patients with plasma cell dyscrasias, and on thromboprophylaxis approaches. While bleeding complications are relatively uncommon in patients with lymphoproliferative disorders, acquired von Willebrand syndrome, typically occurring in patients with monoclonal gammopathy of unknown significance, and acquired coagulopathies associated with primary amyloidosis can present with haemorrhagic complications and both are challenging to manage. This review highlights these important haemostasis-related complications of plasma cell dyscrasias and provides an overview of other uncommon bleeding and thrombotic events that can affect diagnostic and therapeutic management of clonal plasma cell disorders. Due to the infrequency of most of these haemostasis complications, available information is typically based on retrospective cases or series.
    British Journal of Haematology 03/2009; 145(2):151-63. DOI:10.1111/j.1365-2141.2008.07577.x · 4.71 Impact Factor
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