In vitro enhanced chemotaxis of CD25+ mononuclear cells in patients with familial IgAN through glomerulotubular interactions.
Tubulointerstitial infiltration of immunocompetent cells is often associated with a more rapid progression in IgA nephropathy (IgAN). Using an in vitro Transwell coculture system, we examined the chemotactic response of peripheral blood mononuclear cells to proximal tubular epithelial cells (PTEC) following activation by conditioned medium prepared from mesangial cells cultured with macromolecular IgA1 from 60 patients with multiplex familial IgAN (MpIgAN) and 91 of their asymptomatic relatives; 43 patients with sporadic IgAN (SpIgAN) and 90 of their asymptomatic relatives; and 43 healthy subjects. Compared with SpIgAN patients, PTEC activated by conditioned medium from patients with MpIgAN had elevated gene expression of a spectrum of C-C, C-X-C chemokines and proinflammatory cytokines, with prominent expressions of interleukin-6, interleukin-8, and tumor necrosis factor-alpha. In response to conditioned medium from patients with familial IgAN, there was a significant increase in chemotaxis of CD45+ cells, CD3+, CD4+, CD8+, CD20+ lymphocytes, and monocytes with CD25 expression. Our findings suggest that compared with SpIgAN patients, macromolecular IgA1 taken from MpIgAN patients is more pathogenic to cultured PTEC through a glomerulotubular interaction. A long-term follow-up is needed to better define the prognostic course for familial IgAN and to clarify the risk of developing IgAN in initially asymptomatic relatives from a multiplex IgAN family.
Tam
Ka Ying
KY
Department of Medicine, Queen Mary Hospital, University of Hong Kong, China.
Leung
Joseph C K
JC
Chan
Loretta Y Y
LY
Lam
Man Fai
MF
Tang
Sydney C W
SC
Lai
Kar Neng
KN
D016022:Case-Control Studies; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D007687:Kidney Tubules, Proximal / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D050527:Mesangial Cells / Q000276:immunology / Q000473:pathology; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D017077:Culture Media, Conditioned; D016207:Cytokines; C508017:IL2RA protein, human; D007070:Immunoglobulin A; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit