Following the discovery that suppressor of cytokine signaling 3 (SOCS3) is predominantly expressed in Th2 but not Th1 cells (J Immunol. 168:3181-7, 2002), it was revealed that expression of SOCS3 by peripheral blood mononuclear cells (PBMC) of patients with asthma or atopic dermatitis is elevated compared with healthy people. In addition, it was also shown that the severity of these Th2-mediated diseases correlated with the level of SOCS3 mRNA in PBMC (Nat Med 9, 1047-54, 2003). This has led to the suggestion that SOCS3 is a potential new target for anti-allergy drugs. Thereafter, it was established that SOCS5 is preferentially expressed in Th1 but not Th2 cells, leading to the notion that whereas SOCS3 is a molecular marker of Th2 cells, SOCS5 is a Th1 cell marker. Uveitis is a Th1-mediated disease and therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents. However, adverse side effects make long-term therapy difficult. Long-term humanized anti-IL-2 receptor alpha (Daclizumab) therapy has recently been shown to have few side effects and be as effective as standard immunosuppression for treating severe uveitis. An essential component of Daclizumab therapy is careful monitoring of the levels of activated T-cells in the eye in order to allow prompt re-institution of standard immunosuppressive therapy to non-responders. Although the presence of infiltrating cells can easily be diagnosed by fundoscopy, monitoring response to anti-uveitis therapy often relies on fluorescene angiography and some patients are allergic to the dye. In this study we explored the potential use of SOCS5 mRNA as a surrogate marker to monitor the intensity of uveitis and the response of patients to anti-uveitis therapy. We analyzed peripheral blood mononuclear cells (PBMC) of uveitis patients before and after Dacluzimab therapy and our preliminary studies indicate a correlation between the levels of SOCS3 and SOCS5 mRNA levels in PBMC and disease activity. Compared to healthy volunteers, SOCS5 mRNA is elevated in uveitis patients while SOCS3 level is decreased, suggesting that SOCS5 mRNA level in PBMC may reflect the disease intensity and this is consistent with well documented bias towards a Th1 repertoire in uveitis. In addition, we found that Daclizumab therapy induces significant diminution in SOCS5 mRNA level. Reciprocal changes in SOCS5 and SOCS3 expression in PBMC of these patients thus suggest that changes in SOCS mRNA levels may be a potential pathological marker of uveitis. As blood collection is a relatively non-invasive procedure, SOCS5 and SOCS3 mRNA levels in PBMC can therefore be used as diagnostic tools to monitor response of uveitis patients to therapy. This preliminary study also suggests that SOCS5 may serve as a new therapeutic target for uveitis and other autoimmune diseases
| Egwuagu, C E; Li, W; Yu, C-R et al. (2006) Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors. Oncogene 25:3670-9 |
| Takase, H; Yu, C-R; Liu, X et al. (2005) Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins. J Neuroimmunol 168:118-27 |
| Egwuagu, Charles E; Yu, Cheng-Rong; Li, Zhuqing et al. (2005) SOCS5 mRNA levels in peripheral blood mononuclear cells (PBMC): a potential bio-marker for monitoring response of uveitis patients to Daclizumab therapy. J Autoimmun 24:39-46 |
| Li, W; Nagineni, C N; Ge, H et al. (1999) Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens. J Biol Chem 274:9686-91 |
