IP Library › Granted Patent US 12669512
Granted Patent B2
US 12669512 · App. 17/918,449 · Granted Jun 30, 2026

Protein diagnostic biomarker for severe cutaneous drug adverse reactions

Inventors: Yoshiro Saito (Kanagawa, JP); Ryosuke Nakamura (Kanagawa, JP); Noriaki Arakawa (Kanagawa, JP); Yasuo Ohno (Kanagawa, JP); Takashi Izumi (Kanagawa, JP); Motonobu Sato (Ibaraki, JP); Takayoshi Nishiya (Tokyo, JP); Michiko Aihara (Kanagawa, JP)
Assignees: JAPAN AS REPRESENTED BY DIRECTOR GENERAL OF NATIONAL INSTITUTE OF HEALTH SCIENCES; TOSOH CORPORATION
G01N33/6893G01N33/94G01N2800/50G01N2800/56
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Quick Facts
Patent No.
US 12669512
App. No.
17/918,449
Granted
Jun 30, 2026
Kind
B2
Abstract

Biomarkers for diagnosing the disease activity, disease severity or disease type of severe cutaneous adverse drug reactions (SCARs) such as drug-induced hypersensitivity syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis are provided. Also provided is a method of testing SCARs, comprising measuring the expression of at least one protein selected from the group consisting of stratifin, TNF receptor superfamily member 8 (CD30/TNFRSF8), interleukin-1 receptor antagonist (IL-1Ra), and TNF receptor superfamily member 6B (DcR3/TNFRSF6B) in a sample derived from a subject.

Claims (37)

1 . A method of diagnosing and treating severe cutaneous adverse drug reactions, comprising:

a. obtaining a sample from a subject;

b. measuring an expression value of at least one protein selected from the group consisting of stratifin, TNF receptor superfamily member 8 (CD30/TNFRSF8), interleukin-1 receptor antagonist (IL-1Ra), and TNF receptor superfamily member 6B (DcR3/TNFRSF6B) in the sample from the subject;

c. assessing a severity of drug eruption based on the measured expression value of the at least one protein from b; and

d. in the case it is determined from c that the subject is highly likely to develop or has developed severe cutaneous adverse drug reactions, stopping an administration of a suspect drug which was being administered to the subject, and starting an appropriate treatment according to the severity of the drug eruption assessed in c, and

wherein the appropriate treatment is at least one selected from the group consisting of systemic corticosteroid treatment, intravenous immunoglobulin (IVIG) treatment, cyclosporine treatment, plasma exchange treatment, and anti-tumor necrosis factor (TNF) monoclonal antibody treatment.

2 . The method of claim 1 , further comprising measuring an expression value of at least one protein selected from the group consisting of granulysin (GNLY) and C-C motif chemokine 17 (TARC/CCL17) in the sample from the subject.

3 . A method of diagnosing and treating severe cutaneous adverse drug reactions, comprising:

a. obtaining a sample from a subject;

b. measuring an expression value of at least one protein selected from the group consisting of stratifin, TNF receptor superfamily member 8 (CD30/TNFRSF8), interleukin-1 receptor antagonist (IL-1Ra), and TNF receptor superfamily member 6B (DcR3/TNFRSF6B) in the sample from the subject;

c. determining a disease activity of severe cutaneous adverse drug reactions based on the measured expression value of the at least one protein from b; and

d. if it is determined in c that the subject is highly likely to be in an acute phase, stopping an administration of a suspect drug which was being administered to the subject, and starting an appropriate treatment, and

wherein the appropriate treatment is at least one selected from the group consisting of systemic corticosteroid treatment, intravenous immunoglobulin (IVIG) treatment, cyclosporine treatment, plasma exchange treatment, and anti-tumor necrosis factor (TNF) monoclonal antibody treatment.

4 . The method of claim 3 , further comprising measuring an expression value of at least one protein selected from the group consisting of granulysin (GNLY) and C-C motif chemokine 17 (TARC/CCL17) in the sample from the subject.

5 . A method of diagnosing and treating severe cutaneous adverse drug reactions, comprising:

a. obtaining a sample from a subject;

b. measuring an expression value of at least one protein selected from the group consisting of stratifin, TNF receptor superfamily member 8 (CD30/TNFRSF8), interleukin-1 receptor antagonist (IL-1Ra), and TNF receptor superfamily member 6B (DcR3/TNFRSF6B) in the sample from the subject;

c. determining a disease type of severe cutaneous adverse drug reactions based on the measured expression value of the at least one protein from b; and

d. stopping an administration of a suspect drug which was being administered to the subject, and starting an appropriate treatment according to the disease type of severe cutaneous adverse drug reactions determined in c, and

wherein the appropriate treatment is at least one selected from the group consisting of systemic corticosteroid treatment, intravenous immunoglobulin (IVIG) treatment, cyclosporine treatment, plasma exchange treatment, and anti-tumor necrosis factor (TNF) monoclonal antibody treatment.

6 . The method of claim 5 , further comprising measuring an expression value of at least one protein selected from the group consisting of granulysin (GNLY) and C-C motif chemokine 17 (TARC/CCL17) in the sample from the subject.

7 . The method of claim 5 , wherein the protein whose expression value is to be measured is at least one combination of proteins selected from the group consisting of a combination of stratifin and C-C motif chemokine 17 (TARC/CCL17) and a combination of stratifin and TNF receptor superfamily member 8 (CD30/TNFRSF8).

8 . The method according to claim 1 , wherein the appropriate treatment is systemic corticosteroid treatment.

9 . The method according to claim 1 , wherein the appropriate treatment is intravenous immunoglobulin (IVIG) treatment.

10 . The method according to claim 1 , wherein the appropriate treatment is cyclosporine treatment.

11 . The method according to claim 1 , wherein the appropriate treatment is plasma exchange treatment.

12 . The method according to claim 1 , wherein the appropriate treatment is anti-tumor necrosis factor (TNF) monoclonal antibody treatment.

13 . The method according to claim 3 , wherein the appropriate treatment is systemic corticosteroid treatment.

14 . The method according to claim 3 , wherein the appropriate treatment is intravenous immunoglobulin (IVIG) treatment.

15 . The method according to claim 3 , wherein the appropriate treatment is cyclosporine treatment.

16 . The method according to claim 3 , wherein the appropriate treatment is plasma exchange treatment.

17 . The method according to claim 3 , wherein the appropriate treatment is anti-tumor necrosis factor (TNF) monoclonal antibody treatment.

18 . The method according to claim 5 , wherein the appropriate treatment is systemic corticosteroid treatment.

19 . The method according to claim 5 , wherein the appropriate treatment is intravenous immunoglobulin (IVIG) treatment.

20 . The method according to claim 5 , wherein the appropriate treatment is cyclosporine treatment.

21 . The method according to claim 5 , wherein the appropriate treatment is plasma exchange treatment.

22 . The method according to claim 5 , wherein the appropriate treatment is anti-tumor necrosis factor (TNF) monoclonal antibody treatment.