PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Poster Allergologie und Immunologie
P 6
IL-22 and Th2 cytokines predominate in acute cutaneous graft-versus-host
disease.
Marie-Charlotte Brueggen 1
Irene Klein 1
Hildegard Greinix 2
Wolfgang Bauer 1
Zoya Kuzmina 2
Werner Rabitsch 2
Robert Knobler 3
Georg Stingl 1
Georg Stary 1
1 Department of Dermatology, DIAID, Medical University of Vienna
2 Department of Internal Medicine I, Bone Marrow Transplantation, Medical University
of Vienna
3 Department of Dermatology, Division of General Dermatology, Medical University of
Vienna, Währinger Gürtel 18-20, A-1090 Vienna
Introduction: Graft-versus-host disease (GvHD) is the major clinical complication of
allogeneic hematopoietic stem cell transplantation (HCT) occurring in an acute and
chronic form. We still do not understand the pathomechanisms leading to the distinct
clinical presentations of GvHD.
Methods: To address this issue, we collected lesional skin biopsies of patients suffering
from acute (aGvHD) (n=22) and chronic inflammatory (cGvHD) (n=15) GvHD as well as
serial biopsies of non-lesional skin from HCT recipients at different time points prior
and after HCT (n=14). The cellular infiltrate was analyzed by immunofluorescence
stainings; interleukins and chemokines were assessed by real-time RT-PCR.
Results: While CD4+ and CD8+ T-cells dominated the inflammatory infiltrate in both
acute and chronic GVHD, analysis of the quality of the T cell-mediated immune response
revealed striking differences between the two forms. In aGvHD lesions, there was a
predominance of Th2 cytokines (IL-4, IL-13) and Th2 chemokines (CCL17, CCL22). To our
great surprise, levels of IL-22 but not IL-17 were also highly increased in aGvHD but not
in cGvHD skin lesions, suggesting that IL-22 single-producing are major effector cells
in aGvHD. In accordance with these findings, levels of TSLP, a keratinocyte-derived
cytokine skewing the immune response towards a Th2 direction, were increased at day
20 after HCT in non-lesional skin of patients who would later develop aGvHD. The
immune response occurring in cGvHD skin lesions was characterized by a Th1 pattern,
as evidenced by a relative increase of Th1 chemokines (CCL5, CCR5, CXCL9, CXCL10) as
well as Th1 (IFN-gamma, IL-12/IL-23p40) and Th17 (IL23p19) cytokines. Our findings
shed new light on the pathomechanisms operative in the different manifestations of
cutaneous GvHD and, furthermore, identify molecular signatures to more accurately
predict and verify the occurrence of this disease.
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