Proteomics

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Serum proteomic analysis of circulating IgA1-containing immune complexes in patients with IgA nephropathy


ABSTRACT: IgA nephropathy (IgAN) is an autoimmune disease that involves galactose-deficient IgA1 (Gal-deficient IgA1) recognized by autoantibodies to form circulating immune complexes (IgA1-IC). Some of these complexes deposit in the glomeruli and induce kidney injury. Gal-deficient IgA1 alone is not sufficient to induce kidney damage. Additional proteins are required to form nephritogenic complexes. In this study, we isolated different molecular forms of serum IgA1, including IgA1-IC, monomeric (mIgA1), and polymeric (pIgA1) by SEC from patients with IgAN and healthy control donors. These three chromatographic fractions of molecular forms of IgA1 were analyzed by LC-MS. An analysis of the proteomes of the IgA1 molecular forms yielded several serum proteins enriched in the IgA1-IC. These proteins were also enriched in patients with IgAN when compared to healthy controls. The ability to characterize the proteome of IgA1-IC provides critical information relevant to IgAN pathogenesis and the nephritogenic characteristics of the ICs.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Mary Cunningham  

LAB HEAD: Matthew B. Renfrow

PROVIDER: PXD055562 | Pride | 2025-11-03

REPOSITORIES: Pride

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Publications

Proteomic Analysis of Circulating IgA1-Containing Immune Complexes in Patients with IgA Nephropathy.

Cunningham Mary A MA   Hargett Audra A AA   Holloway Amanda K AK   Hall Stacy D SD   Craine Ellenore P EP   Maillard Nicolas N   Rizk Dana V DV   Julian Bruce A BA   Novak Jan J   Renfrow Matthew B MB  

Kidney international reports 20250712 10


<h4>Introduction</h4>IgA1-containing immune complexes (IgA1-IC) consisting of galactose-deficient IgA1 (Gal-deficient IgA1) and IgG autoantibodies are central to the pathogenesis of IgA nephropathy (IgAN). These IgA1-IC form in circulation, and additional proteins may be added before the deposition in the glomeruli. However, the composition of these circulating IgA1-IC is not fully understood. To address this gap in knowledge, we developed a novel proteomic workflow.<h4>Methods</h4>IgA1-IC from  ...[more]

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