IP Library Granted Patent US 12,276,663
Granted Patent B2
US 12,276,663 · App. 17/427,887 · Granted Apr 15, 2025

Detection of human leukocyte antigen-A*32:01 in connection with determining drug reaction with eosinophilia and systemic symptoms (DRESS) and methods of treating bacterial infection in a subject with vancomycin-induced DRESS

Inventors: Elizabeth Phillips (Nashville, TN); Simon Mallal (Nashville, TN); Katherine Konvinse (Nashville, TN); Abha Chopra (Nashville, TN)
Assignee: Vanderbilt University
G01N33/56977G01N2333/70539G01N2800/24
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,276,663
App. No.
17/427,887
Granted
Apr 15, 2025
Kind
B2
Abstract

Methods of detecting a human leukocyte antigen (HLA)-A*32:01 allele in a subject as disclosed are useful, for example, to determine whether the subject is at risk for developing or has vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Methods of treating bacterial infection in a subject with vancomycin-induced DRESS are also disclosed.

Claims (27)

1. A method of detecting a human leukocyte antigen (HLA)-A*32:01 allele in a subject, comprising:

(a) obtaining a biological sample from the subject;

(b) detecting whether HLA-A*32:01 is present in the sample using a primer specific for a HLA-A*32 allele to determine whether the subject is at risk for developing or has vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS) when HLA-A*32:01 is present in the sample, wherein the primer specific for HLA-A*32 is HLA 32-88F (SEQ ID NO: 1).

2. The method of claim 1 , wherein the subject has a bacterial infection.

3. The method of claim 2 , wherein the bacteria is an antibiotic-resistant gram-positive bacteria.

4. The method of claim 1 , wherein the biological sample is from a subject suspected of having DRESS.

5. The method of claim 4 , wherein the subject is receiving combination antibiotic treatment that includes vancomycin.

6. The method of claim 5 , wherein the subject is diagnosed as having vancomycin-induced DRESS when the presence of HLA-A*32:01 in the sample is detected.

7. The method of claim 6 , further comprising administering to the diagnosed subject an antibiotic treatment that excludes vancomycin.

8. The method of claim 1 , wherein the biological sample is from a subject in need of treatment with an antibiotic.

9. The method of claim 8 , and further comprising identifying the subject as being at risk for developing vancomycin DRESS when the presence of HLA-A*32:01 in the sample is detected.

10. The method of claim 9 , further comprising administering an antibiotic that is not vancomycin, teicoplanin, telavancin, or a glycopeptide antibiotic to the identified subject.

11. The method of claim 9 , further comprising administering dalbavancin to the identified subject.

12. The method of claim 1 , wherein sequenced-based typing is conducted to determine whether HLA-A*32:01 is present in the sample.

13. The method of claim 1 , wherein SNP2HLA is used to determine whether HLA-A*32:01 is present in the sample.

14. The method of claim 1 , and further comprising using an IFN-γ Enzyme-Linked ImmuneSpot assay.

15. The method of claim 1 , wherein a polymerase chain reaction assay is used to determine whether HLA-A*32:01 is present in the sample.

16. The method of claim 1 , and further using a second primer specific for HLA-A*32 that is HLA032R2 (SEQ ID NO: 2).

17. A kit comprising a primer specific for HLA-A*32, including HLA-A*32 is HLA 32-88F (SEQ ID NO: 1) and HLA-A*32 that is HLA032R2 (SEQ ID NO: 2).

18. A method of identifying risk of developing vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in a subject, comprising:

(a) obtaining a biological sample from the subject; and

(b) detecting whether HLA-A*32:01 is present in the sample using a primer mix containing one or both of HLA 32-88F (SEQ ID NO: 1) and HLA032R2 (SEQ ID NO: 2).

19. A method of diagnosing vancomycin DRESS in a subject and treating the subject for a bacterial infection, comprising:

(a) obtaining a biological sample from the subject;

(b) detecting whether HLA-A*32:01 is present in the sample using a primer mix containing one or both of HLA 32-88F (SEQ ID NO: 1) and HLA032R2 (SEQ ID NO: 2);

(c) diagnosing the subject with, or being at risk of developing, vancomycin DRESS when the presence of HLA-A*32:01 in the sample is detected; and

(d) administering an antibiotic that is not vancomycin to the diagnosed subject.

Assignments (2)
CONFIRMATORY LICENSE Recorded Aug 12, 2022
From: VANDERBILT UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061163/0976 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 2, 2021
From: PHILLIPS, ELIZABETH; MALLAL, SIMON; KONVINSE, KATHERINE; CHOPRA, ABHA
To: VANDERBILT UNIVERSITY
Reel/Frame 057058/0635 →
Continuity (2)
Provisional Application 62805717 · Feb 14, 2019
Related Publication 20220107316A1 · Apr 7, 2022
References Cited (15)
US 7858319B2 · Hetherington et al. · 2010 [cited by applicant]
US 20120135418A1 · Kim et al. · 2012 [cited by applicant]
WO WO2012083240A2 · 2012 [cited by applicant]
WO WO2018232316A1 · 2018 [cited by applicant]
Littlehales, Emma et al. “Vancomycin-Induced DRESS Syndrome: An Important Concern in Orthopedic Surgery.” Case reports in orthopedics vol. 2018 1439073. Jun. 24, 2018, doi: 10.1155/2018/1439073 (Year: 2018). [cited by examiner]
Wolfson, Anna R et al. “Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Identified in the Electronic Health Record Allergy Module.” The journal of allergy and clinical immunology. In practice vol.… [cited by examiner]
Cheng, Changming et al. “Detection of rare point mutation via allele-specific amplification in emulsion PCR.” BMB reports vol. 46,5 (2013): 270-5. doi:10.5483/bmbrep.2013.46.5.155 (Year: 2013). [cited by examiner]
Konvinse et al. “HLA-A*32:01 Is strongly associated with vancomycin-induced drug reaction with eosinophllia and systemic symptoms,” The Journal of Allergy and Clinical Immunology, Feb. 16, 2019 (Feb. 16, 2019), vol. 144… [cited by applicant]
Park et al. “HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs,” Yonsei Medical Journal, Nov. 30, 2015 (Nov. 30, 2019), vol. 57, Iss. 1, pp. 118-126. [cited by applicant]
Roy et al. “Vancomycin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Masquerading as Elusive Sepsis,” Case Reports in Immunology, Apr. 10, 2019 (Apr. 10, 2019), vol. 2019, pp. 1-5. [cited by applicant]
Alfirevic, et al., Drug Induced Hypersensitivity and the HLA Complex, Pharmaceuticals 2011, 4, 69-90. [cited by applicant]
Konvinse KC, Trubiano JA, Pavlos R, James I, Shaffer CM, Bejan CA, Pilkinton MA, Rosenbach M, Zwerner JP, Williams KB, Jack Bourke J, Martinez P, Rwandamuriye F, Chopra A, Watson M, Mallal SA, Redwood A, White KD, Phill… [cited by applicant]
Nakkam N, Trubiano J, Gibson A, Phillips EJ. Considerations for cross-reactivity between vancomycin and other glycopeptides. J Allergy Clin Immunol Pract. Aug. 2021;9(8):3233. [cited by applicant]
Nakkam N, Gibson A, Mouhtouris E, Konvinse KC, Holmes NE, Chua KY, Deshpande P, Li D, Ostrov DA, Trubiano J, Phillips EJ. Cross-reactivity between vancomycin, teicoplanin, and telavancin in patients with HLA-A?32:01-pos… [cited by applicant]
Rwandamuriye FX, Chopra A, Konvinse KC, Choo L, Trubiano JA, Shaffer CM, Watson M, Mallal SA, Phillips EJ. A Rapid Allele-Specific Assay for HLA-A*32:01 to Identify Patients at Risk for Vancomycin-Induced Drug Reaction … [cited by applicant]