Abstract
Both IgA nephropathy and IgA vasculitis, formerly known as Henoch-Schӧnlein purpura, are immune deposition diseases. IgA nephropathy is caused by the deposition of aberrantly formed poly-IgA complexes from blood circulation to the kidney glomerulus; IgA vasculitis is characterized by IgA-dominant immune deposits to small vessels of the skin and other organs, including the kidney. Therefore, measuring the disease-causing poly-IgA contents in the plasma is needed to study these conditions. However, while clinical tests for the level of total plasma IgA are routinely performed, methods for specific detection of poly-IgA contents are unavailable in clinical medicine. In this protocol, we describe a practical solution for measuring poly-IgA in patient samples. The new method is based on the biological selectivity of IgA Fcα receptor I (FcαRI/CD89) toward poly-IgA species, in contrast to its relatively low affinity for normal monomeric IgA. By devising recombinant CD89 ectodomain as the “capturing” probe, wevalidated the feasibility of the assay for measuring plasma poly-IgA levels in a 96-well format. The methodology was able to differentiate plasma samples of IgA nephropathy, or related IgA vasculitis, from those of other autoimmune kidney disease types or from healthy controls. Moreover, the measured poly-IgA indices not only correlated with the severity of IgA nephropathy, but the levels also trended lower following corticosteroid or immunosuppressant treatments of patients. Therefore, we anticipate the new assay will provide useful measurements of the IgA nephropathy disease activity index for stratifying disease severity or for evaluating treatment response.
Original language | English (US) |
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Article number | e4463 |
Journal | Bio-protocol |
Volume | 12 |
Issue number | 13 |
DOIs | |
State | Published - Jul 5 2022 |
Funding
This study was supported by National Natural Science Foundation of China grants 81670649 and 81925006, the Capital Health Development Research Project of China grant 2018-2-4073, Beijing Science and Technology Plan Project of China grant D181100000118003, and CAMS Innovation Fund for Medical Sciences grant 2019-I2M-5-046 (to J. Lv). This protocol was adapted from procedures published in Zhang et al. (2021).
Keywords
- CD89/IgA Fc receptor
- Circulating IgA immune activity index
- ELISA method
- IgA nephropathy
- IgA vasculitis/Henoch-Schӧnlein purpura
- Poly-IgA immune complex
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Neuroscience
- Plant Science