IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Because of its frequently unfavorable cou7rse and lack of specific therapy, IgAN represents a serious healthy care and economic problem. The overall objective of the proposed Program Project is to determine the genetic and molecular basis of this common disease through integrated studies of patients with IgAN or Henoch-Schonlein purpura (HSP), commonly considered the systemic form of the disease process causing IgAN. We will enroll 20 multiplex families with 50 member5s afflicted with IgAN or HSP and 150 other family members; 150 Caucasian patients with sporadic IgAN (no affected relatives) and 375 of their family members, 50 patients with HSP and 125 of their relatives, 50 African-American patients with IgAN and 200 family members, 50 patients with non-IgAN glomerulonephritis, and 200 Caucasians and 100 African-Americans as health controls. This proposal is based on novel findings generated in the laboratories of the participating investigators, with respect to genetic, biosynthetic, and metabolic studies of IgA molecules, immune complexes, and relevant receptors involved in IgA catabolism. The Program Project consists of three component research project and two core facilities: Project 1: Genetic Studies of IgA Nephropathy Project 2: Biosynthesis and Glycosylation of IgA1 Molecules in IgA Nephropathy Project 3: Immune Complexes and Mesangial Cells in IgA Nephropathy Core A: Clinical Resources and Biostatistics Core B: Administrative The results generated through extensive collaboration among the participating investigators are likely to provide information concerning the genetic and molecular defects characteristic of IgAN, identify mechanisms of the pathogenesis of this disease, and ultimately provide a basis to develop rational therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK061525-02
Application #
6623346
Study Section
Special Emphasis Panel (ZDK1-GRB-4 (J2))
Program Officer
Hirschman, Gladys H
Project Start
2002-06-15
Project End
2007-01-31
Budget Start
2003-04-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2003
Total Cost
$1,320,221
Indirect Cost
Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Hastings, M Colleen; Bursac, Zoran; Julian, Bruce A et al. (2018) Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep 3:99-104
Tamouza, Houda; Chemouny, Jonathan M; Raskova Kafkova, Leona et al. (2012) The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy. Kidney Int 82:1284-96
Novak, Jan; Raskova Kafkova, Leona; Suzuki, Hitoshi et al. (2011) IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol Dial Transplant 26:3451-7
Camilla, Roberta; Suzuki, Hitoshi; Daprà, Valentina et al. (2011) Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. Clin J Am Soc Nephrol 6:1903-11
Gomes, Michelle M; Suzuki, Hitoshi; Brooks, Monica T et al. (2010) Recognition of galactose-deficient O-glycans in the hinge region of IgA1 by N-acetylgalactosamine-specific snail lectins: a comparative binding study. Biochemistry 49:5671-82
Good, David M; Zürbig, Petra; Argilés, Angel et al. (2010) Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease. Mol Cell Proteomics 9:2424-37
Lavigne, K A; Woodford, S Y; Barker, C V et al. (2010) Familial IgA nephropathy in southeastern Kentucky. Clin Nephrol 73:115-21
Hastings, M Colleen; Moldoveanu, Zina; Julian, Bruce A et al. (2010) Galactose-deficient IgA1 in African Americans with IgA nephropathy: serum levels and heritability. Clin J Am Soc Nephrol 5:2069-74
Suzuki, Hitoshi; Fan, Run; Zhang, Zhixin et al. (2009) Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 119:1668-77
Mischak, Harald; Coon, Joshua J; Novak, Jan et al. (2009) Capillary electrophoresis-mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis: an update of recent developments. Mass Spectrom Rev 28:703-24

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