Biomarkers for distinguishing acute GVHD from HHV-6B reactivation after hematopoietic stem cell transplantation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16282
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fujita Health University
• Principal Investigator: Miura Hiroki 藤田医科大学, 医学部, 助教 (10751761)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: HHV-6B / 急性GVHD / サイトカイン / バイオマーカー

Outline of Final Research Achievements

Monitoring of HHV-6B reactivation was carried out in hematopoietic cell transplant patients. The group was divided into four groups: HHV-6B reactivation group: 17 cases, skin GVHD group: 13 cases, HHV-6B reactivation and skin GVHD group: 11 cases and control group which were not recognized both HHV-6B reactivation and skin GVHD: 18 cases. Eleven kinds of cytokines and chemokines were measured from serum that collected from patients at 1, 2, 3, 4 and 6 weeks after hematopoietic cell transplantation.
In HHV-6B reactivation group, IL-2, 4, 6, 10 at week 2, IL-10, IP-10 at week 3, IP-10, TNF-α at week 6 were significantly increased compared to the control group. In skin GVHD group, IL-4, 17 at week 2, IL-4, 10, IP-10 at week 3, and IL-10, 17 at week 6 were significantly increased compared to the control group.
Rader charts showed that the figures on the 1st and 2nd weeks were similar in the A and B groups, but the figures on the 3rd, 4th and 6th weeks were different between these groups.

Free Research Field

ヘルペスウイルス

Academic Significance and Societal Importance of the Research Achievements

HHV-6Bは同種造血幹細胞移植患者で移植後2から4週間に再活性化し、急性GVHDの好発時期に一致し、臨床症状からHHV-6B再活性化に伴うウイルス性発疹症と真の皮膚GVHDの鑑別は困難である。急性GVHDに対してはステロイド治療を行うが、HHV-6B再活性化に対しては抗ウイルス薬の投与が必要であり、ステロイド治療はむしろ感染を助長する危険性がある。本研究によって移植後のサイトカインプロファイルを行うことで両者を鑑別できる可能性を見出した。このことは移植後種々の合併症に対する適切な治療選択に有用であるだけでなく、不要な治療を回避することで医療費の削減にも寄与する可能性がある。