Yukiko Takakuwa, MD,
,
Division of Rheumatology and Allergy, Department of Internal Medicine, Machida Municipal Hospital, Machida, Japan
Manae Kurokawa, MD, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Seido Ooka, MD, PhD
,
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
Sato Toshiyuki, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Nagai Kouhei, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Arito Mitsumi, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Naoya Suematsu, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Kazuki Okamoto, MD, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Hiroko Nagafuchi, MD, PhD,
,
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
Hidehiro Yamada, MD, PhD
,
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
Shoichi Ozaki, MD, PhD
,
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
Kato Tomohiro, MD, PhD,
,
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
Background: Microscopic polyangiitis (MPA) is necrotizing vasculitis with unknown etiology. To find a biomarker, we explored serum peptidome of MPA.
Methods: Serum peptides from 33 patients with MPA, 7 with Wegener’s granulomatosis, 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 ELISA and real-time PCR.
Results: 102 serum peptides were detected from the 78 patients. One of the peptides, p1523, showed significantly higher ion intensity in MPA (46.8±39.3AU) than that in the other systemic vasculitis (14.1±12.2AU, p<0.05) and SLE (17.0±12.1AU, p<0.05). In MPA, p1523 showed significantly higher ion intensity before treatment than 1 week (p<0.05) and 6 weeks (p<0.05) after the initiation of treatment. p1523 was identified as C-terminal 13 amino acid residues of apolipoprotein A-I (ApoAI), designated as “AC13”. Validation of AC13 ion intensity using another MPA cohort (n=14) similarly showed significantly higher ion intensity (90.1±167.9AU) compared to 14 patients with rheumatoid arthritis (8.6±5.4AU, p<0.01) and 14 healthy subjects (11.8±6.1AU, p<0.01). Concentration of serum ApoAI and high density lipoprotein-cholesterol was downregulated 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 upregulated secretion of IL-6 (p<0.05) and IL-8 (p<0.05).
Conclusions: AC13, a candidate biomarker for MPA, may be useful for monitoring the disease-activity, and may exacerbate the vascular inflammation through upregulation of the proinflammatory cytokines.
