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Abstract: PO1448

Immune Complexes in the Peripheral Blood of Patients with IgA Nephropathy Contain Polymeric Galactose-Deficient IgA1 Associated with IgG and Complement C3

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Hall, Stacy D., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Coffee, Sarah, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Maillard, Nicolas, The University of Alabama at Birmingham, Birmingham, United States
  • Moldoveanu, Zina, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Craine, Ellenore P., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hargett, Audra A., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Rizk, Dana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Julian, Bruce A., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Renfrow, Matthew B., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Novak, Jan, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

IgA nephropathy (IgAN) is an autoimmune disease wherein immune complexes (IC) consisting of IgA1 with some hinge-region O-glycans deficient in galactose (Gd-IgA1) and IgG autoantibodies deposit in the kidneys and induce injury. Although the glomerular immunodeposits are enriched for Gd-IgA1, not much is known about the distribution of different molecular forms of Gd-IgA1 in circulation.

Methods

Total serum IgA1 was isolated from 7 Caucasian and 10 African American patients with IgAN by jacalin -affinity chromatography. Different molecular forms of IgA1 were then separated by size-exclusion chromatography (SEC). Gd-IgA1 was detected by lectin ELISA. IgA1-IC were isolated by SEC from sera of 4 IgAN patients. Biological activity of the isolated IC was assessed measuring the proliferation of cultured primary human mesangial cells (MC). IgA1, IgG, and complement C3 were analyzed by SDS-PAGE/immunoblotting.

Results

Total serum IgA1 included monomeric and polymeric forms and IgA1 bound in IC. Monomeric IgA1 represented ~88-92% of total IgA1, whereas polymeric IgA1 represented ~8-12%. IgA1 in IC was the least abundant form, representing <0.4% of total IgA1. Relative representation of Gd-IgA1 was highest in IC, followed by polymeric forms, and lowest in monomeric forms. Gd-IgA1 in IC had minimally sialylated O-glycans, whereas polymeric and monomeric forms were substantially sialylated. Caucasian patients had higher content of Gd-IgA1 in polymeric and monomeric forms of IgA1 compared to those of African American patients (P<0.03 and P<0.05, respectively). IgA1-IC in sera of IgAN patients had molecular mass >700 kDa and stimulated proliferation of MC. These IC consisted of polymeric IgA1, IgG, and complement C3.

Conclusion

Biologically active IC in the circulation of IgAN patients contain polymeric, minimally sialylated Gd-IgA1 associated with IgG and C3. These findings support the pathogenic role of Gd-IgA1-IgG IC in IgAN.

Funding

  • NIDDK Support