TCR repertoire analysis targeting HTLV-1-infected cells in HAM patients for biomarker discovery

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22879
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kagoshima University
• Principal Investigator: Satoshi Nozuma 鹿児島大学, 医歯学域医学系, 助教 (40884052)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: HTLV-1関連脊髄症 / 神経免疫性疾患 / 神経感染症 / T細胞受容体レパトア解析 / HTLV-1

Outline of Final Research Achievements

HTLV-1-infected cells in peripheral blood and CSF cells from HAM patients were targeted for TCR repertoire analysis using molecular barcodes. This analysis revealed a higher clonal expansion in HTLV-1-infected cells and a higher number of HTLV-1 infected cells with polyclonal expansion in HAM patients. The TCR repertoire of infected cells was unique to each patient, and the repertoire signatures were retained over time. Infected cell clones proliferating in the central nervous system showed a different distribution than those in the peripheral blood and were considered to be pathogenic clones that cause inflammation in the CNS of HAM patients.
Our results indicate that TCR repertoire analysis in HTLV-1-infected cells of HAM patients could be used to identify pathogenic clones. Tracking the pathogenic clones longitudinally and across organs is expected as biomarkers for disease monitoring and therapeutic indicators.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

分子バーコードを用いたバイアスのないTCRレパトア解析のパイプラインを確立した。TCRレパトア解析により、HAM患者で病原性のあるHTLV-1感染細胞クローンは個々の患者に特有のものであり、長期に保存されていること、また中枢神経系では末梢血と異なる分布を示すことが判明した。これらの病原性のあるHTLV-1感染細胞クローンの同定・追跡は、疾患活動性の指標や治療介入時のバイオマーカーとして利用できるなど、テーラーメード医療への応用が可能となると考える。