AC13, a C‐terminal fragment of apolipoprotein A‐I, is a candidate biomarker for microscopic polyangiitis

Objective Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease. Methods Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg‐Strauss...

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Published in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-11, Vol.63 (11), p.3613-3624
Main Authors: Takakuwa, Yukiko, Kurokawa, Manae S., Ooka, Seido, Sato, Toshiyuki, Nagai, Kouhei, Arito, Mitsumi, Suematsu, Naoya, Okamoto, Kazuki, Nagafuchi, Hiroko, Yamada, Hidehiro, Ozaki, Shoichi, Kato, Tomohiro
Format: Article
Language:English
Subjects:
Adult
Aged
Apolipoprotein A-I - blood
Biological and medical sciences
Biomarkers
Churg-Strauss Syndrome - blood
Diseases of the osteoarticular system
Female
Granulomatosis with Polyangiitis - blood
Humans
Male
Medical sciences
Microscopic Polyangiitis - blood
Middle Aged
Peptide Fragments - blood
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
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Summary:Objective Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease. Methods Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg‐Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction. Results A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C‐terminal amino acid residues of apolipoprotein A‐I (Apo A‐I) and was designated “AC13.” Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A‐I and high‐density lipoprotein cholesterol were down‐regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up‐regulated secretion of interleukin‐6 (IL‐6) (P < 0.05) and IL‐8 (P < 0.01). Conclusion AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up‐regulation of proinflammatory cytokines.
ISSN:0004-3591
2326-5191
1529-0131
2326-5205
DOI:10.1002/art.30560