Cytokine patterns <i>in vitro</i>, in particular IL‐5/IL‐8 ratio, to detect patients with nickel contact allergy

Summer, Burkhard; Ständer, Sascha; Thomas, Peter A.

doi:10.1111/jdv.14931

Cited by 14 publications

(38 citation statements)

References 42 publications

(62 reference statements)

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“…However, no significant differences between allogenic or autologous serum were reported in a MELISA test study 27 . Despite the discrepancies among these reports, which might be due to a high level of variability between human serum lots, the use of autologous serum seems to be on the rise, 28‐30 which is strongly supported by our results.…”

Section: Discussionsupporting

confidence: 91%

Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel

Graaf

Bontkes

Roffel

et al. 2020

Clin Experimental Allergy

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Background: Skin patch testing is still seen as the gold standard for the diagnosis of allergic hypersensitivity. For several metals and for patients with a suspected adverse reaction to their medical device implant material, patch testing can be unreliable. The current alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LPT) using tritiated thymidine. This method is well-established but requires handling of radioactive material, often uses heat-inactivated allogenic human pooled serum and cannot determine T cell subsets. Objective: To develop a radioactive free LPT by using carboxyfluorescein succinimidyl ester (CFSE) and to evaluate the influence of serum source (heat-inactivated human pooled serum [HI HPS] vs autologous serum) on the sensitivity and specificity of the nickel-specific LPT. Methods: Peripheral blood mononuclear cells derived from nickel-allergic patients and healthy controls were collected, labelled with CFSE and cultured in medium containing 10% HI HPS or 10% autologous serum with or without additional T cell skewing cytokine cocktails (Th1: IL-7/IL-12, Th2: IL-7/IL-4 or Th17: IL-7/IL-23/IL-1β) in the absence or presence of NiSO 4 . The stimulation index (SI) was calculated as the ratio of divided cells, that is the percentage of CFSE low/neg CD3 + CD4 + T-lymphocytes upon nickel stimulation compared to the percentage of CFSE low/neg CD3 + CD4 + T-lymphocytes without antigen. These results were compared with the history of Ni allergy, patch test results and the MELISA test.Results: Autologous serum positively influenced Ni-specific proliferation while HI HPS negatively influenced Ni-specific proliferation. The test protocol analysing CD4 + cells and autologous serum without skewing cytokines scored the best diagnostic values (sensitivity 95%; specificity 93%; and overall accuracy 94%) compared to the parallel test using HI HPS (accuracy 60%). Cytokine supplements did not further improve the test protocol which used autologous serum. The protocol using HI HPS could be further improved by addition of the cytokine skewing cocktails. | 723 de GRAAF et Al.

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Section: Discussionsupporting

confidence: 91%

Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel

Graaf

Bontkes

Roffel

et al. 2020

Clin Experimental Allergy

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“…Given the level of sensitivity, the number of false negatives, and interlaboratory variation, the lymphocyte transformation test seems very unlikely to be a replacement for patch testing, but does have the advantages that additional endpoints such as the identity of the proliferating cells (CD4 or CD8) or the nature of cytokine production can be incorporated to improve mechanistic understanding. 7,47,48 In addition to sensitization being associated with changes in the profile of naïve and effector/central memory and EMRA cells, we also observed that, particularly for extremely allergic individuals, the Treg frequency was decreased, as was the CD4 + /CD8 hi ratio, whereas CLA expression was increased. These findings appeared to be a feature of sensitization to each of the three different allergens, despite the fact that they have very different chemistries.…”

Section: Discussionmentioning

confidence: 58%

“…45 The reasons for this lower share of positivity in our study are not clear, although it is noted that minor technical differences in the lymphocyte transformation test protocol can have marked effects, such as the use of autologous serum, 46 or the length of time in culture (5 days vs 6 or 7 days). 39,40,47 The lowest number of responders (5/12) was recorded for the extremely (+++) sensitized group, although mean proliferation was similar between the ++ and + ++ groups. This inverse dose-response relationship may indicate that the culture conditions were not optimal, rather than a true negative correlation of proliferation with patch test sensitivity.…”

Section: Discussionmentioning

confidence: 93%

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

et al. 2019

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Background: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds.Objectives: To examine the relationship between patch test score for three different contact allergens and the characteristics of T cell responses.Methods: A total of 192 patients with confirmed nickel, p-phenylenediamine (PPD) or methylisothiazolinone (MI) allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by the use of patch testing, peripheral blood lymphocytes were characterized for T cell phenotype by flow cytometry, and proliferative activity was characterized by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers.Results: Patch test positivity for nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T cells: increases in naïve cells, decreases in regulatory T cell frequency and the CD4 + /CD8 hi ratio, and increased expression of the skin-homing marker cutaneous lymphocyte antigen (CLA), particularly for those patients with a +++ patch test score.Conclusions: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters with which to better measure health risks associated with skin sensitization. K E Y W O R D SCD4, CD8, inverted CD4/CD8, skin-homing CLA, lymphocyte transformation test, T cell phenotype, RRID:SCR_001905

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“…IL‐8, which is usually upregulated in in vitro evaluation of the sensitizing potential of chemicals in dendritic and THP‐1 cells, was inhibited by nickel in this test. Therefore, Summers et al . calculated the IL‐5/IL‐8 ratio, a measure which slightly increased the sensitivity of the in vitro test, but at the expense of a reduced specificity.…”

mentioning

confidence: 99%

“…IL-8, which is usually upregulated in in vitro evaluation of the sensitizing potential of chemicals in dendritic and THP-1 cells, was inhibited by nickel in this test. Therefore, Summers et al 4 calculated the IL-5/IL-8 ratio, a measure which slightly increased the sensitivity of the in vitro test, but at the expense of a reduced specificity. This is not yet the definite answer to resolve the limitations of in vitro testing in the diagnosis of contact allergy, but the combination of different in vitro techniques with inclusion of measurement of T-cell cytokines may be an important aspect to explore, as observed in non-immediate drug eruptions.…”

mentioning

confidence: 99%

New attempts to improve in vitro diagnosis of contact allergy are still far from regular clinical practice

Gonçalo

2018

Acad Dermatol Venereol

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Cytokine patterns in vitro, in particular IL‐5/IL‐8 ratio, to detect patients with nickel contact allergy

Abstract: Assessment of the ratio of Ni-induced IL-5 and reduced IL-8 production in vitro is a helpful tool for a better characterization of Ni-allergic patients.

Cited by 14 publications

References 42 publications

Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel

Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

New attempts to improve in vitro diagnosis of contact allergy are still far from regular clinical practice

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