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Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold
Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Dermatology and Venerology UHL.
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2006 (English)In: Contact Dermatitis, ISSN 0105-1873, Vol. 55, no 2, 101-112 p.Article in journal (Refereed) Published
Abstract [en]

10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

Place, publisher, year, edition, pages
2006. Vol. 55, no 2, 101-112 p.
Keyword [en]
Allergic contact dermatitis, cytokines, gold, interferon-γ, lymphocyte transformation test, multibead assay
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-20564DOI: 10.1111/j.1600-0536.2006.00908.xPubMedID: 16930235OAI: diva2:235124
Available from: 2009-09-14 Created: 2009-09-14 Last updated: 2009-09-14Bibliographically approved
In thesis
1. Gold allergy: In vitro studies using peripheralblood mononuclear cells
Open this publication in new window or tab >>Gold allergy: In vitro studies using peripheralblood mononuclear cells
2009 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.

In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.

We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.

In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.

In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 67 p.
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 102
National Category
Dermatology and Venereal Diseases
urn:nbn:se:liu:diva-20565 (URN)978-91-7393-591-3 (ISBN)
2009-09-11, Seminarierummet AIR, Campus US, Linköpings Universitet, Linköping, 10:00 (Swedish)
Available from: 2009-09-14 Created: 2009-09-14 Last updated: 2009-09-15Bibliographically approved

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Christiansen Clifford, JennyAnderson, ChrisCederbrant, KarinHultman, Per
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Molecular and Immunological PathologyFaculty of Health SciencesDermatology and Venerology Department of Dermatology and Venerology UHLMolecular and Immunological Pathology Department of Clinical Pathology and Cytology
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