Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy

Abstract

The Fc-α receptor (FcαR/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.

Current Understanding of the Role of Complement in IgA Nephropathy

“…An association between the levels of sCD89-IgA complexes in serum and the severity of IgAN has been observed. 104 Specifically, patients with IgAN without disease progression had high levels of sCD89 in contrast to low levels of sCD89 in the disease progression group, suggesting that sCD89-IgA complexes may be protective. In contrast, an animal model suggested that interaction between four entities-Gd-IgA1, sCD89, transferrin receptor, and transglutaminase 2 in mesangial cells-is needed for disease development.…”

Immunoglobulin A nephropathy: a pathophysiology view

“…As a consequence, cleavage of the extracellular domain of FcaRI is induced, leading to the formation of circulating IgA/FcaRI immune complexes, which are found in mesangial deposits. IgA/FcaRI immune complexes have been implicated in disease exacerbation through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney [40,[89][90][91].…”

Diagnosis and monitoring of IgA nephropathy: the role of biomarkers as an alternative to renal biopsy

“…The increase of IgA-soluble CD89 (sCD89) complexes in the serum of patients with IgAN has been reported [18,27]. However, the exact role of sCD89 in mesangial IgA1 deposit formation and disease progression remains indefinite and could involve an interaction with the TfR and other unknown molecular mechanisms.…”

“…An association between the serum levels of sCD89-IgA complexes and the severity of IgAN has been reported. The single-nucleotide polymorphism rs11084377 is probably one of the genetic regulators of the production or expression of sCD89 [27].…”