Pathogenese der Psoriasis-Arthritis

Zusammenfassung

Psoriasis und Psoriasis-Arthritis sind eng miteinander verknüpfte Syndrome, deren Symptomatik und Krankheitsverlauf auf verschiedene genetische und nichtgenetische Faktoren zurückzuführen sind. Die Pathogenese beider Syndrome wird über immunologische Prozesse vermittelt. Neben dem adaptiven Immunsystem spielen auch Mechanismen angeborener Immunität eine entscheidende Rolle. Unterschiede der Pathogenese beider Manifestationen finden sich in den Lymphozytenpopulationen, die beide Syndrome vermitteln. Diese interagieren intensiv mit den ortsständigen Zellen. Das monozytäre Phagozytensystem spielt als Effektor vor allem in der terminalen Differenzierung zu Osteoklasten und im Rahmen der Vaskulogenese eine wichtige Rolle. Therapeutische Ansätze bestehen im Bereich der angeborenen (u. a. TNF-Blockade) und adaptiven Immunität (u. a. über IL-12, IL-23). Im Vergleich zur Klinik der rheumatoiden Arthritis finden sich Verläufe sehr unterschiedlicher Ausprägung, die oft asymmetrisch verlaufen. Gemeinsamkeiten bestehen zur Klinik der Spondylitis ankylosans im Auftreten von Enthesiopathien und Daktylitiden.

Summary

The pathogenesis of both, psoriasis and psoriatic arthritis are linked based on different genetic and non-genetic origins. Immunological processes including adaptive immune system and mechanism of innate immunity are important properties. The pathogenesis varies in the disease-connected populations of lymphocytes and the interaction with the local cells. Main effector-cells are monocytes which lead to differentiation of osteoclasts and effects in the vasculogenesis. Therapeutic strategies besides innate immunity (e. g. TNF-blockade) involve adaptive immunitiy (e. g. IL-12, IL-23) as well. Compared to the clinical manifestations of rheumatoid arthritis, the disease pattern of psoriatic arthritis is different and the joint involvement is often asymmetric. Similarities are enthesiopathies and dactylitis compared to other manifestations of spondylarthritis.

Schlüsselwörter

Psoriasis - Psoriasis-Arthritis - TNF-alpha - Lymphozyten

Keywords

Psoriasis - psoriatic arthritis - TNF-alpha - lymphocytes

• Literatur

• 1 Balding J, Kane D, Livingstone W. et al. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 2003; 48 (05) 1408-1413.
• 2 Cook PW, Piepkorn M, Clegg CH. et al. Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype. J Clin Invest 1997; 100 (09) 2286-2294.
• 3 Diluvio L, Vollmer S, Besgen P. et al. Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris. J. Immunol 2006; 176 (11) 7104-7111.
• 4 Gonzalez S, Martinez-Borra J, Torre-Alonso JC. et al. The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis. Arthritis Rheum 1999; 42 (05) 1010-1016.
• 5 Höhler T, Kruger A, Schneider PM. et al. A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis. J Invest Dermatol 1997; 109 (04) 562-565.
• 6 Johnston A, Gudjonsson JE, Sigmundsdottir H. et al. Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. Clin. Exp. Immunol 2004; 138 (01) 83-93.
• 7 Kämpfer H, Kalina U, Mühl H. et al. Counterregulation of interleukin-18 mRNA and protein expression during cutaneous wound repair in mice. J. Invest. Dermatol 1999; 113 (03) 369-374.
• 8 Kane D, Lockhart JC, Balint PV. et al. Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint). Ann Rheum Dis 2005; 64 (02) 325-327.
• 9 Lande R, Gregorio J, Facchinetti V. et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007; 449 (7162): 564-569.
• 10 McGonagle D, Lories R, Tan A, Benjamin M. The Concept of a “Synovio-Entheseal Complex” and Its Implications for Understanding Joint Inflammation and Damage in Psoriatic Arthritis and Beyond. Arthritis Rheum 2007; 56 (08) 2482-2491.
• 11 McGonagle D, Marzo-Ortega H, Benjamin M, Emery P. Report on the Second international Enthesitis Workshop. Arthritis Rheum 2003; 48 (04) 896-905.
• 12 Moll JM, Wright V. Familial occurrence of psoriatic arthritis. Ann Rheum Dis 1973; 32 (03) 181-201.
• 13 Myers A, Kay LJ, Lynch SA, Walker DJ. Recurrence risk for psoriasis and psoriatic arthritis within sibships. Rheumatology (Oxford) 2005; 44 (06) 773-776.
• 14 Nair RP, Stuart P, Henseler T. et al. Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C. Am J Hum Genet 2000; 66 (06) 1833-1844.
• 15 Nestle FO, Conrad C, Tun-Kyi A. et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 2005; 202 (01) 135-143.
• 16 Ohta Y, Hamada Y, Katsuoka K. Expression of IL-18 in psoriasis. Arch Dermatol Res 2001; 293 (07) 334-342.
• 17 Pietrzak A, Lecewicz-Torun B, Chodorowska G, Rolinski J. Interleukin-18 levels in the plasma of psoriatic patients correlate with the extent of skin lesions and the PASI score. Acta Derm Venereol 2003; 83 (04) 262-265.
• 18 Pitzalis C, Cauli A, Pipitone N. et al. Cutaneous lymphocyte antigen-positive T lymphocytes preferentially migrate to the skin but not to the joint in psoriatic arthritis. Arthritis Rheum 1996; 39 (01) 137-145.
• 19 Rahman P, Gladman DD, Schentag CT, Petronis A. Excessive paternal transmission in psoriatic arthritis. Arthritis Rheum 1999; 42 (06) 1228-1231.
• 20 Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003; 111 (06) 821-831.
• 21 Romphruk AV, Romphruk A, Choonhakarn C. et al. Major histocompatibility complex class I chain-related gene A in Thai psoriasis patients: MICA association as a part of human leukocyte antigen-B-Cw haplotypes. Tissue Antigens 2004; 63 (06) 547-554.
• 22 Sano S, Chan KS, Carbajal S. et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005; 11 (01) 43-49.
• 23 Sugiyama H, Gyulai R, Toichi E. et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 2005; 174 (01) 164-173.
• 24 Tsunemi Y, Nishibu A, Saeki H. et al. Lack of association between the promoter polymorphisms at positions –308 and –238 of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese patients. Dermatology (Basel) 2003; 207 (04) 371-374.
• 25 Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL. et al. Psoriasis- as an autoimmune disease caused by molecular mimicry. Trends Immunol 2009; 30 (10) 494-501.
• 26 Zenz R, Eferl R, Kenner L. et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 2005; 437 (7057): 369-375.
• 27 Zhou X, Krueger JG, Kao MJ. et al. Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiol Genomics 2003; 13 (01) 69-78.
• 28 Xia Y, Li B, Hylton D. et al. Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 2003; 102 (01) 161-168.