Elevated antilysosomal-associated membrane protein-2 antibody levels in patients with adult Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is characterized by IgA-containing immune complexes within leucocytoclastic vasculitis. Lysosomal-associated membrane protein-2 (LAMP-2) was first identified as part of a systematic search for antineutrophil cytoplasmic antibody (ANCA) antigens expressed on neutrophils and endothelial cells.
OBJECTIVES: To investigate the presence of ANCA in patients with adult HSP and microscopic polyangiitis (MPA), and to measure serum LAMP-2 antibody levels in these patients.
METHODS: Twenty-four adult patients with HSP, eight with MPA and 24 normal healthy controls were examined. ANCA detection was performed using indirect immunofluorescence (IIF), a direct enzyme-linked immunosorbent assay (ELISA) and a capture ELISA specific for myeloperoxidase (MPO) and proteinase 3 (PR3). We measured other ANCA-associated antibodies including anti-LAMP-2 antibody in serum using ELISA. Immunohistochemical (IHC) staining was used for anti-LAMP-2 antibody expression in patient skin biopsies. To determine the cut-off value of the serum anti-LAMP-2 antibody, a receiver operating characteristic (ROC) curve was constructed using statistical analysis software (JMP 8·0·2; SAS Institute Inc., Cary, NC, U.S.A.).
RESULTS: The sera of all patients with HSP were negative for MPO-ANCA and PR3-ANCA by direct ELISA and by capture ELISA. However, ANCA was present in 17 (71%) of the 24 patients with HSP based on IIF. In contrast, we found MPO-ANCA in all eight patients with MPA using both ELISA methods. We found serum anti-LAMP-2 antibody levels in HSP significantly higher than in MPA and in healthy individuals (P = 0·002 and P = 0·00167, respectively). The area under the curve of serum anti-LAMP-2 antibody between HSP and MPA was 0·8698 by ROC analysis. The optimal cut-off point was 0·267 U mL(-1) (sensitivity 1·000, specificity 0·583). We found a significant positive correlation between serum anti-LAMP-2 antibody levels and serum IgA levels in HSP (r(s) = 0·731, P = 0·00226). Anti-LAMP-2 antibody overexpression in IHC staining was present in 20 (83%) of the patients with HSP. The overexpression was observed within the neutrophils and endothelial cells of leucocytoclastic vasculitis. There was a significant positive correlation between IHC staining score and positive serum anti-LAMP-2 antibody. The 24 patients with HSP and the eight patients with MPA were negative for antiazurocidin antibodies, antibactericidal permeability increasing protein antibodies, anticathepsin G antibodies, antielastase antibodies, antilactoferrin antibodies and antilysozyme antibodies.
CONCLUSIONS: We suggest that anti-LAMP-2 antibody could play some role in the pathogenesis of adult HSP, and have excluded a role for MPO-ANCA and PR3-ANCA. We propose that measuring serum anti-LAMP-2 antibody could be a feasible method of differential diagnosis between HSP and MPA.