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November 21, 2022
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LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study

Publicated to:Frontiers in Pharmacology. 13 959321- - 2022-10-20 13(), DOI: 10.3389/fphar.2022.959321

Authors: Bellón T, Lerma V, Guijarro J, Ramírez E, Martínez C, Escudero C, Fiandor AM, Barranco R, de Barrio M, de Abajo F, Cabañas R, PIELenRed Study Group

Affiliations

Autonomous Univ Madrid, Hosp Univ Paz Carlos III Cantoblanco, Sch Med, Clin Pharmacol Dept,IdiPAZ, Madrid, Spain - Author
Hosp Gregorio Maranon, Allergy Dept, Madrid, Spain - Author
Hosp Univ Doce Octubre, Allergy Dept, Madrid, Spain - Author
Hosp Univ Nino Jesus, Allergy Dept, Madrid, Spain - Author
Hosp Univ Paz Carlos III Cantoblanco, Allergy Dept, Madrid, Spain - Author
Hosp Univ Paz IdiPaz, Drug Hypersensit Lab, Inst Hlth Res, Madrid, Spain - Author
Hosp Univ Principe Asturias, Clin Pharmacol Unit, Madrid, Spain - Author
Hospital General Universitario Gregorio Marañón - Author
Hospital Infantil Universitario Niño Jesús de Madrid - Author
Hospital Universitario 12 de octubre - Author
Hospital Universitario La Paz - Author
Instituto de Investigación Sanitaria del Hospital Universitario La Paz - Author
Univ Alcala IRYCIS, Dept Biomed Sci, Madrid, Spain - Author
Universidad de Alcalá , Hospital Universitario Príncipe de Asturias - Author
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Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher’s exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364–130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28–252.6; p = 4.0 × 10−3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.

Keywords

allergydressdrug causality algorithmdrug hypersensitivitydrug reactioneosinophiliaepidemiologyfeatureshlahypersensitivitylttpatchsevere cutaneous adverse reactionssystemic symptomsvancomycinDressDrug causality algorithmDrug hypersensitivityHlaLttLymphocyte-transformation testSevere cutaneous adverse reactionsVancomycin

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers in Pharmacology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 44/278, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.05. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.84 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 5.03 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-18, the following number of citations:

  • WoS: 4
  • Scopus: 7

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-18:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 8.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 9 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.25.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.