Clinical trial NCT00365625: Determination of Lymphocyte JAM-C Expression in Patients With Psoriasis Vulgaris
Official title: Patient Orientated Basic Science Investigation: Determination of Lymphocyte JAM-C Expression in Patients With Psoriasis Vulgaris
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Psoriasis
Psoriasis Vulgaris
Keywords: Psoriasis
JAM3 protein, human
Cell Adhesion Molecules
Skin
Inflammation
Lymphocytes
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2006-08-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: psoriasis patients

Brief summary: The stepwise process of leukocyte extravasation to inflamed tissues depends on the expression of a variety of cytokines and adhesion molecules. Recently much attention has focused on the Junctional Adhesion Molecules (JAM). The three members of this adhesion molecule family, namely, JAM-A, -B and -C, have been shown to govern the last step of leukocyte extravasation (transmigration) - the process of leukocytes passing between endothelial cells. In addition to transmigration, some members of this family seem to support additional steps in the leukocyte extravasation cascade. The investigators recently showed, that antibody-mediated inhibition of JAM-C significantly reduced hapten induced skin inflammation (J Invest Dermatol;125(5):969).

Recent unpublished work from our laboratory showed, that JAM-C expression of lymphocytes can be up-regulated through specific activators. Hence, the investigators hypothesize, that JAM-C expression is elevated in patients with psoriasis. As it is currently not know, which factors may influence the expression of JAM-C, the investigators intend to analyse JAM-C expression on CD3+CD41- cells at several time-points during the treatment of psoriatic patients. Expression of JAM-C will then be correlated to disease activity (PASI).

Detailed description: The stepwise process of leukocyte extravasation to inflamed tissues depends on the expression of a variety of cytokines and adhesion molecules. Recently much attention has focused on the Junctional Adhesion Molecules (JAM). The three members of this adhesion molecule family, namely, JAM-A, -B and -C, have been shown to govern the last step of leukocyte extravasation (transmigration) - the process of leukocytes passing between endothelial cells. In addition to transmigration, some members of this family seem to support additional steps in the leukocyte extravasation cascade. We recently showed, that antibody-mediated inhibition of JAM-C significantly reduced hapten induced skin inflammation (J Invest Dermatol;125(5):969).

Recent unpublished work from our laboratory showed, that JAM-C expression of lymphocytes can be up-regulated through specific activators. Hence, we hypothesize, that JAM-C expression is elevated in patients with psoriasis. As it is currently not know, which factors may influence the expression of JAM-C, we intend to analyse JAM-C expression on CD3+CD41- cells at several time-points during the treatment of psoriatic patients. Expression of JAM-C will then be correlated to disease activity (PASI).

Detailed in- and exclusion criteria are outlined below.

Eligibility criteria: Inclusion Criteria:

* Psoriasis vulgaris
* PASI \>/= 10 at inclusion

Exclusion Criteria:

* Psoriasis arthritis
* Psoriasis pustulosa
* Psoriasis palmoplantaris
* Pregnancy
* current infectious disease

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Frankfurt Am Main
country: Germany
facility: Department of Dermatology - Clinic of the Johann Wolfgang Goethe University
state: Hessen
Study officials:
affiliation: Department of Dermatology - Clinic of the Johann Wolfgang Goethe University
name: Ralf J Ludwig, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Dermatology - Clinic of the Johann Wolfgang Goethe University
name: Roland Kaufmann, Professor
role: STUDY_CHAIR
affiliation: Department of Dermatology - Clinic of the Johann Wolfgang Goethe University
name: Wolf-Henning Boehncke, Professor
role: STUDY_CHAIR
References:
citation: Ludwig RJ, Zollner TM, Santoso S, Hardt K, Gille J, Baatz H, Johann PS, Pfeffer J, Radeke HH, Schon MP, Kaufmann R, Boehncke WH, Podda M. Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation. J Invest Dermatol. 2005 Nov;125(5):969-76. doi: 10.1111/j.0022-202X.2005.23912.x.
citation: Santoso S, Sachs UJ, Kroll H, Linder M, Ruf A, Preissner KT, Chavakis T. The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. J Exp Med. 2002 Sep 2;196(5):679-91. doi: 10.1084/jem.20020267.
citation: Chavakis T, Keiper T, Matz-Westphal R, Hersemeyer K, Sachs UJ, Nawroth PP, Preissner KT, Santoso S. The junctional adhesion molecule-C promotes neutrophil transendothelial migration in vitro and in vivo. J Biol Chem. 2004 Dec 31;279(53):55602-8. doi: 10.1074/jbc.M404676200. Epub 2004 Oct 14.
citation: Muller WA. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003 Jun;24(6):327-34. doi: 10.1016/s1471-4906(03)00117-0.
citation: Vonlaufen A, Aurrand-Lions M, Pastor CM, Lamagna C, Hadengue A, Imhof BA, Frossard JL. The role of junctional adhesion molecule C (JAM-C) in acute pancreatitis. J Pathol. 2006 Aug;209(4):540-8. doi: 10.1002/path.2007.
citation: Santoso S, Orlova VV, Song K, Sachs UJ, Andrei-Selmer CL, Chavakis T. The homophilic binding of junctional adhesion molecule-C mediates tumor cell-endothelial cell interactions. J Biol Chem. 2005 Oct 28;280(43):36326-33. doi: 10.1074/jbc.M505059200. Epub 2005 Aug 23.
citation: Lamagna C, Hodivala-Dilke KM, Imhof BA, Aurrand-Lions M. Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth. Cancer Res. 2005 Jul 1;65(13):5703-10. doi: 10.1158/0008-5472.CAN-04-4012.
citation: Aurrand-Lions M, Lamagna C, Dangerfield JP, Wang S, Herrera P, Nourshargh S, Imhof BA. Junctional adhesion molecule-C regulates the early influx of leukocytes into tissues during inflammation. J Immunol. 2005 May 15;174(10):6406-15. doi: 10.4049/jimmunol.174.10.6406.