SEREX ANALYSIS OF IPF PATIENS : DEMONSTRATION OF SOME AUTOANTIGENS REACTED WITH CD4 POSITIVE T CELLS IN BRONCHOALVEOLAR LAVAGE FLUIDS

• Project/Area Number: 15590798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: KUROSU Katsushi chiba University, Graduate School of Medicine, Department of Respirology, Instructor, 大学院・医学研究院, 助手 (20291106)
• Co-Investigator(Kenkyū-buntansha): TAKIGUCHI Yuichi Chiba University, Graduate School of Medicine, Department of Respirology, Assistant Professor, 医学部附属病院, 講師 (30272321) ; TATSUMI Koichiro Chiba University, Graduate School of Medicine, Department of Respirology, Associate Professor, 大学院・医学研究院, 助教授 (10207061) ; KURIYAMA Takayuki Chiba University, Graduate School of Medicine, Department of Respirology, Professor, 大学院・医学研究院, 教授 (20009723)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
• Keywords: SEREX / idiopathic pulmonary fibrosis / CD4 positive lymphocyte / Vβ chain / autoantibodies / 間質性肺炎 / 自己抗原

Research Abstract

The natural history of idiopathic lung fibrosis(IPF) is invariably one of gradual and progressive deterioration, with median length of survival from the time of diagnosis ranging 2.5-3.5 yrs, it still remains uncertain what causes such clinical deterioration. To identify antigens that may play a role in the context of PF, a cDNA phage library of type II alveolar cell carcinoma (A549) cell lines were screened using sera of 14 patients with IPF using serological analysis of the cDNA expression library(SEREX). Our experiments included an analysis of TCR-Vb repertoire and oligoclonality of CD4 positive T cells in bronchoalveolar lavage fluid(BALF). Our results showed that CD4 positive T cells in BALF of some patients with IPF expand oligoclonally, suggesting antigen-driven stimulation by recognizing a restricted epitope on the major histocompatibility complex through TCR. In cases 2, two TCR-Vb rearrangements (TCR-Vb2 and Vb7) in BAL sample on DGGE were identical to those in the VATS biopsy (2 months later). This suggests that some infiltrating CD4 positive T cells in BALF shared epitopes on autoantigens. Autoantibodies to annexin I, phosphoglyverate kinase 1, annexin IV, bax inhibitor 1, and cytochrome c oxidase subunit Va was detected in 4 to 5 of 12 patients with IPF. The CDR3 region of identical TCR-Vb7 clones in both BALF and VATS samples in case 2 have high homology with the portion (residues 20-26) of annexin 1. This region was included in epitopes of annexin 1 selected by TEPITOPE analysis with DRB1 0410 and DRB1 1307 (HLA-DR

Research Products

• [Journal Article] BCL-6 Mutations in Pulmonary Lymphoproliferative Disorders (2004)
  • Author(s): K.KUROSU, et al.
  • Journal Title: J.Immunology 172 Pages: 7116-7122
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] T.BCL-6 Mutations in Pulmonary Lymphoproliferative Disorders : Demonstration of an Aberrant Immunological Reaction in HIV-Related Lymphoid Interstitial Pneumonia. (2004)
  • Author(s): K Kurosu, Weiden MD, Takiguchi Y, Rom WN, N Yumoto, Jaishree J, Nakata K, Y, Kasahara, N Tanabe, K Tatsumi, Mikata A, T Kuriyama
  • Journal Title: J.Immunol 172 Pages: 7116-7122
  • Description: 「研究成果報告書概要(欧文)」より