Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis.
Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti-LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti-LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti-LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti-proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti-LAMP-2 titers, respectively. There was no correlation between anti-LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti-LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti-LAMP-2 antibodies and ANCA glomerulonephritis.
University of North Carolina Kidney Center, Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ajroth@med.unc.edu
Aleeza J
AJ
Roth
Michael C
MC
Brown
Rex Neal
RN
Smith
Anshul K
AK
Badhwar
Oscar
O
Parente
Hyun chul
Hc
Chung
Donna O'Dell
DO
Bunch
JulieAnne G
JG
McGregor
Susan L
SL
Hogan
Yichun
Y
Hu
Jia-Jin
JJ
Yang
Elisabeth A
EA
Berg
John
J
Niles
J Charles
JC
Jennette
Gloria A
GA
Preston
Ronald J
RJ
Falk
D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects / Q000097:blood*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D015995:Prevalence; D051381:Rats; D011921:Rats, Inbred WKY; D012680:Sensitivity and Specificity; D014552:Urinary Tract Infections / Q000097:blood / Q000276:immunology* / Q000382:microbiology
D000888:Antibodies, Anti-Idiotypic; D019268:Antibodies, Antineutrophil Cytoplasmic; D052119:Lysosomal-Associated Membrane Protein 2; D009195:Peroxidase; D053146:Myeloblastin