Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance.
Department of Medicine, University of Hong Kong, Hong Kong.
Kwok Fan
KF
Cheung
Department of Medicine, University of Hong Kong, Hong Kong.
Susan
S
Yung
Department of Medicine, University of Hong Kong, Hong Kong.
Mel K M
MK
Chau
Department of Medicine, University of Hong Kong, Hong Kong.
Desmond Y H
DY
Yap
Department of Pathology, University of Hong Kong, Hong Kong.
Kwok Wah
KW
Chan
Hong Kong Red Cross Blood Transfusion Service, Hong Kong.
Cheuk Kwong
CK
Lee
Department of Medicine, University of Hong Kong, Hong Kong.
Colin S O
CS
Tang
Department of Medicine, University of Hong Kong, Hong Kong dtmchan@hku.hk ssyyung@hku.hk.
Tak Mao
TM
Chan
D000328:Adult; D000818:Animals; D017306:Annexin A2 / Q000097:blood*; D000974:Antibodies, Antinuclear / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D007668:Kidney / Q000473:pathology; D008137:Longitudinal Studies; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008875:Middle Aged; D012720:Severity of Illness Index
D017306:Annexin A2; D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins
annexin II; anti-dsDNA antibodies; disease activity; immune complex deposition; lupus nephritis