PMID- 34757063
OWN - NLM
STAT- MEDLINE
DCOM- 20220218
LR  - 20220218
IS  - 2213-2201 (Electronic)
VI  - 10
IP  - 2
DP  - 2022 Feb
TI  - Serum Soluble OX40 as a Diagnostic and Prognostic Biomarker for Drug-Induced 
      Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms.
PG  - 558-565.e4
LID - S2213-2198(21)01195-8 [pii]
LID - 10.1016/j.jaip.2021.10.042 [doi]
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with 
      eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction 
      commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There 
      are currently no adequate biomarkers for the early diagnosis and detection of 
      DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation 
      and functions as a cellular receptor for HHV-6 entry. We previously reported that 
      the membrane-bound form of OX40 in CD4(+) T cells was upregulated in DIHS/DRESS. 
      OBJECTIVE: We sought to investigate the clinical significance of serum soluble 
      OX40 (sOX40) in DIHS/DRESS. METHODS: Serum sOX40 levels in patients with 
      DIHS/DRESS (n = 39), maculopapular exanthema/erythema multiforme (n = 17), 
      Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 13), or autoimmune 
      bullous diseases (n = 5), and levels in healthy volunteers (n = 5) were examined 
      by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and 
      cytomegalovirus in peripheral blood mononuclear cells were quantified using 
      real-time PCR. RESULTS: Serum sOX40 levels in patients with DIHS/DRESS in the 
      acute stage were elevated in parallel with high OX40 expression on CD4(+) T 
      cells. Serum sOX40 levels were significantly positively correlated with disease 
      severity and serum levels of thymus and activation-regulated chemokine, IL-5, and 
      IL-10. Human herpesvirus 6-positive patients had higher sOX40 levels than did 
      HHV-6-negative patients, and serum sOX40 levels were correlated with HHV-6 DNA 
      loads. CONCLUSIONS: Serum sOX40 levels can be a useful diagnostic marker for 
      DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also 
      predict HHV-6 reactivation in patients with DIHS/DRESS.
CI  - Copyright (c) 2021 American Academy of Allergy, Asthma & Immunology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Mitsui, Yasuhiro
AU  - Mitsui Y
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Shinkuma, Satoru
AU  - Shinkuma S
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Nakamura-Nishimura, Yuki
AU  - Nakamura-Nishimura Y
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Ommori, Rie
AU  - Ommori R
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Ogawa, Kohei
AU  - Ogawa K
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Miyagawa, Fumi
AU  - Miyagawa F
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan.
FAU - Mori, Yasuko
AU  - Mori Y
AD  - Division of Clinical Virology, Center for Infectious Diseases, Kobe University 
      Graduate School of Medicine, Kobe, Japan.
FAU - Tohyama, Mikiko
AU  - Tohyama M
AD  - Department of Dermatology, National Hospital Organization Shikoku Cancer Center, 
      Matsuyama, Japan.
FAU - Asada, Hideo
AU  - Asada H
AD  - Department of Dermatology, Nara Medical University School of Medicine, Kashihara, 
      Japan. Electronic address: asadah@naramed-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211028
PL  - United States
TA  - J Allergy Clin Immunol Pract
JT  - The journal of allergy and clinical immunology. In practice
JID - 101597220
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - *Drug Hypersensitivity Syndrome/diagnosis
MH  - *Eosinophilia
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - *Pharmaceutical Preparations
MH  - Prognosis
OTO - NOTNLM
OT  - CD134
OT  - DIHS
OT  - DRESS
OT  - HHV-6
OT  - OX40
OT  - Thymus and activation-regulated chemokine
EDAT- 2021/11/11 06:00
MHDA- 2022/02/19 06:00
CRDT- 2021/11/10 14:38
PHST- 2021/05/09 00:00 [received]
PHST- 2021/09/07 00:00 [revised]
PHST- 2021/10/15 00:00 [accepted]
PHST- 2021/11/11 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/11/10 14:38 [entrez]
AID - S2213-2198(21)01195-8 [pii]
AID - 10.1016/j.jaip.2021.10.042 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol Pract. 2022 Feb;10(2):558-565.e4. doi: 
      10.1016/j.jaip.2021.10.042. Epub 2021 Oct 28.