Wanted to share my research on PsA ... If anyone is interested
The research study Reduction of Synovial Sublining Layer Inflammation and Proinflammatory Cytokine Expression in Psoriatic Arthritis Treated with Methotrexate attempted to determine the impact of methotrexate on inflammation and cytokine expression in patients with psoriatic arthritis (Kane et al., 2004). Researchers are working to better understand Psoriatic Arthritis (PsA) was discovered officially in the 1970’s by John Moll and Verna Wright which a variant of rheumatoid arthritis (RA) spicifically associated with psoriasis and generally negative of rheumatoid factor (Moll & Wright, 1973). Psoriatic arthritis is associated with proinflammatory cytokines that cause skin lesions and affects the joints of the hands, feet, knees, and ankles (McCance & Huether, 2010). Five specified patterns were identified by Moll and Wright (1973), including distal joint disease, spondylitis, oligoarthritis, arthritis mutilans and symmetric polyarthritis. Originally thought to be less destructive than RA, the severity of PsA includes, “significant progression of joint damage and a mortality risk” (Gladman, 2012, p. 106)
Kane et al. (2004) found that using methotrexate reduced synovial inflammatory infiltrates and proinflammatory cytokines, specifically IL-8. However, methotrexate did not “reduce hypervascularity, which is a prominent differentiating feature of PsA synovium” (Kane et al., 2004, p. 3286) Cytokines found in PsA synovium include IL-15, IFNy, IL-1B, and TNFa and anti-inflammatory cytokine IL-10. The study showed some reduction in IL-1a, IL-1B, IL-8, IL-10, IL-15, IFNy, and TNFa however the only significant reduction was in IL-8 (Kane et al., 2004). Study participants included 10 patients with PsA in an active state affecting a knee joint. Each participant underwent synovial knee biopsy including synovial lining (Kane et al., 2004). Samples of three joint locations were also taken from each patient. Kane et al. (2004) used Monocolonal antibodies primarily mouse IgG1 isotype and immunohistochemical staining. They also included the use of synovial sections with an identifiable lining layer (Kane et al., 2004). Total RNA was extracted from synovial tissue and complimentary DNA was reverse transcribed from RNA samples and used for reaction results.
The study showed significant improvement in the Ritchie Articular Index, swollen joint count and Disease Activity Score (DAS) following the use of methotrexate over 11.5 months (Kane et al., 2004). Erythrocyte sedimentation rate and C-reactive protein levels were also lower however not significant. Synovial lining thickening showed reduction as well as the percentage on inflammatory infiltrates decreased with the use of methotrexate (Kane et al., 2004). Specifically Kane et al. (2004) found the “frequency of IL-1a was reduced from 70% of patients to 30% of patients following treatment” (p. 3292). Kane et al. (2004) found methotrexate to reduce lymphocyte and monocyte infiltration, IL-1a, IL-1B, IL-8, IL-10, IL-15, IFNy, and TNFa mRNA expression, and adhesion marker expression in PsA. Whereas in RA the decrease is in IL-1B (12,13) and TNFa (17,21), and cytokine-induced expression of adhesion molecules (20,21). Kane et al. (2004) concluded that methotrexate reduces synovial membrane T-cell and macrophage infiltrates and proinflammatory cytokine gene expression; however a reduction in hypervascularity did not occur. Kane et al. (2004) concurred that further research into the role of IL-8, IL-15 and IFNy, and T-cell studies will provide specific knowledge on PsA and what inflammatory factors need to be controlled to decrease symptoms and stop joint deterioration.
Due to the complexity of the inflammatory role of autoimmune responses in patients with PsA it is important for clinicians to be prepared to used medications such as methotrexate along with NSAIDS, other DMARDS, and Biologic drugs to ultimately find what works best for each patient uniquely. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was formed in 2003 to increase knowledge and recognition for PsA (Gladman, 2012). Research in genetic markers, comorbidities, and patient-reported outcome measures are to be aspects of future studies (Gladman, 2012). Currently anti-TNF agents or biologic such as Humira, Embrel, Simponi, and Remicade have been affective in diminishing inflammatory response 40% of patients on these therapies still show active inflammation occurring (Gladman, 2012). New and more effective treatments need to be discovered in the fight against PsA and other autoimmune diseases affecting patients today.
I feel I have not completely grasped all that is involved in the immune process and I will continue to read and study these concepts as part of a lifelong effort to understand PsA.
References
Gladman, D. (2012). Future trends in research in psoriatic arthritis. The Journal of Rheumatology, Suppl 89, 106-110. http://dx.doi.org/10.3899/jrheum.120259
Kane, D., Gogarty, M., O’Leary, J., Sila, I., Bermingham, N., Bresnihan, B., & FitzGerald, O. (2004). Reduction of sunovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Arthritis & Rheumatism, 50, 3286-3295. http://dx.doi.org/10.1002/art.20518
McCance, K., & Huether, S. (2010). The integumentry system. In V. Brashers, & N. Rote (Eds.), Pathophysiology the biologic basis for disease in adults and children (6th ed., Ch. 44). Maryland Heights, MO: Mosby Elsevier.
Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78.