AC13, a C-Terminal Fragment of Apolipoprotein A-I, Is a Candidate Biomarker for Microscopic Polyangiitis

作者：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

来源：Arthritis and Rheumatism, 2011, 63(11): 3613-3624.

DOI：10.1002/art.30560

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 hig-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 upregulation of proinflammatory cytokines.

• 出版日期2011-11