High titer anti-basement membrane antibodies in a subset of patients with pediatric systemic lupus erythematosus.
OBJECTIVE
There is a critical need for more noninvasive biomarkers to identify nephritis in patients with systemic lupus erythematosus (SLE). Recent studies in a model mouse and an adult SLE patient cohort suggest that anti-basement membrane antibody levels correlate well with lupus activity and kidney injury. The purpose of this study was to assess the anti-basement membrane reactivity in pediatric SLE (pSLE) patients with or without nephritis.


METHODS
Auto-antibodies to basement membrane antigens were assessed using an anti-matrigel ELISA. Endpoint titers were measured in pSLE patients and healthy children, as well as in autoimmune and non-immune mice, with good reproducing capabilities. Findings were also analyzed with respect to the presence or absence of nephritis, dsDNA antibodies, and other manifestations of pSLE.


RESULTS
MRL/lpr mice developed high-titer anti-matrigel antibodies, whereas C57BL/6 mice did not. In a cohort of 21 pSLE patients and 22 pediatric controls, high-titer anti-matrigel IgG, IgM and IgA antibody levels were specific for pSLE. High-titer anti-matrigel IgG3 levels could distinguish with good sensitivity the 13 pSLE patients with a history of nephritis from the 8 non-renal pSLE patients. High-titer anti-matrigel IgG, IgA, IgM or IgG3 did not correlate with positive anti-double stranded DNA, but defined an overlapping subset of patients.


CONCLUSIONS
The addition of anti-basement membrane antibody testing to serologic testing in pSLE may help to monitor disease activity or to define important subsets of patients with risks for specific disease manifestations.
Department of Pediatrics, Baylor College of Medicine, Houston, Tex., USA.
Alvaro
A
Orjuela
Adisak
A
Suwanichkul
Debra
D
Canter
Charles G
CG
Minard
Sridevi
S
Devaraj
M John
MJ
Hicks
Eyal
E
Muscal
Scott E
SE
Wenderfer
D000293:Adolescent; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001485:Basement Membrane / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000276:immunology; D008181:Lupus Nephritis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C048844:anti-IgG; D004247:DNA