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Int J Clin Exp Pathol 2013;6(6):1103-1111

Original Article
Expression analysis of leukocytes attracting cytokines in chronic histiocytic
intervillositis of the placenta

Lukas Freitag, Constantin von Kaisenberg, Hans Kreipe, Kais Hussein

Institute of Pathology, Hannover Medical School, Hannover, Germany; Department of Gynaecology and Obstetrics, Hannover Medical School,
Hannover, Germany

Received March 18, 2013; Accepted April 23, 2013; Epub May 15, 2013; Published June 1, 2013

Abstract: Chronic histiocytic intervillositis of the placenta (CHI) is a rare and potentially recurrent disease. Characteristically it shows
accumulation of CD68+ cells in the intervillous space but no destructive tissue infiltration. An immunopathological background is likely but it is
unknown what attracts circulating monocytes to the placenta. Methods: We analysed the expression profile of 102 inflammation- and
angiogenesis-associated genes with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 16 placentas: CHI (n = 5) and, as
controls, villitis of unknown aetiology (VUE, n = 4) and normal placenta (n = 7). Results: Compared to controls, CHI had significantly higher
levels of matrix metallopeptidase 9 (MMP9) and transforming growth factor, beta receptor 1 (TGFBR1). MMP14 was lower in VUE than CHI (p <
0.05) and controls (not significant). Chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL12, chemokine (C-C motif) ligand 5 (CCL5) and TIMP
metallopeptidase inhibitor 1 (TIMP1) were significantly higher in VUE versus controls but not deregulated in CHI. The expression profile could
not clearly discriminate CHI from VUE or controls but a tendency for grouping of massive CHI was found. Angiogenesis-associated factors
were not deregulated in CHI. Conclusion: The discrepancy of massive histiocytic accumulation and the lack of striking up-regulation of
cytokines might be the basis of the non-destructive behaviour of the histiocytes in CHI. (IJCEP1303042).

Keywords: Cytokine, chemokine, histiocyte, monocyte, placenta pathology, chronic histiocytic intervillositis, massive perivillous histiocytosis

Address correspondence to: Dr. Kais Hussein, Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover,
Germany.Tel: 0049-511-532-4501; Fax: 0049-511-532-5799; E-mail: Hussein.Kais@MH-Hannover.de