title: SOCS5 mRNA levels in peripheral blood mononuclear cells (PBMC): a potential bio-marker for monitoring response of uveitis patients to Daclizumab therapy.
abstract: Uveitis is an intraocular inflammatory disease mediated by Th1 lymphocytes. Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. Long-term humanized anti-interleukin-2 (IL-2) receptor alpha (Daclizumab) therapy has few side effects and is as effective as standard immunosuppression for treating severe uveitis. However, it is necessary to carefully monitor levels of activated T cells in the eye to allow prompt re-institution of standard immunosuppressive therapy to non-responders to Daclizumab therapy. Suppressors of cytokine signaling (SOCS) are feedback regulators of Th1/Th2 cytokines. SOCS5 and SOCS3 are preferentially expressed in Th1 and Th2 cells, respectively, and are thought to be lineage markers for T-helper cells. In this study, we have investigated whether SOCS3 or SOCS5 expression can serve as surrogate markers of T-cell levels in the eye. Compared to healthy volunteers, SOCS5 mRNA is significantly elevated in PBMC of uveitis patients while SOCS3 is decreased. However, after Daclizumab therapy SOCS5 mRNA level is significantly decreased, suggesting that SOCS5 mRNA can be used as diagnostic tool to monitor therapeutic response of uveitis patients. Our data also suggest that SOCS5 may serve as a new therapeutic target for uveitis and other autoimmune diseases.
authors.affiliation: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. egwuaguc@nei.nih.gov
authors.forename: Charles E
authors.initials: CE
authors.lastname: Egwuagu
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Yu
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Li
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000077561:Daclizumab; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000235:genetics; D014605:Uveitis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C106644:SOCS3 protein, human; C408990:SOCS5 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D000077561:Daclizumab