Aberrant Expression of Soluble Co-stimulatory Molecules and Adhesion Molecules in Type 2 Diabetic Patients with Nephropathy C. K. Wong & Amy W. Y. Ho & Peter C. Y. Tong & C. Y. Yeung & Juliana C. N. Chan & Alice P. S. Kong & Christopher W. K. Lam Received: 21 August 2007 / Accepted: 17 September 2007 / Published online: 17 November 2007 # Springer Science + Business Media, LLC 2007 Abstract Co-stimulatory molecules together with leuko- cyte adhesion molecules are important for T lymphocyte and leukocyte-mediated inflammatory responses. We inves- tigated the soluble costimulatory molecules CD80, CD86, CD28, and CTLA-4 and soluble adhesion molecules in plasma of 94 type 2 diabetic patients with or without nephropathy (DN and NDN) and 20 healthy controls. Plasma concentration of sCTLA-4 was significantly lower, whereas sCD28 was significantly higher in DN patients than that in control subjects (all P <0.05). sCD28 and sCD80 were found to be positively correlated with fasting urine albumin: creatinine ratio in DN patients but not in NDN patients. Elevated soluble adhesion molecule vascular cell adhesion molecule-1 and P-selectin could be related with the disease severity of DN (all P <0.05). Therefore, the aberrant expression of soluble co-stimulatory molecules and adhesion molecules can be related to the activation of T cells and leukocytes in the progression of inflammation in diabetic nephropathy. Keywords Adhesion molecules . Co-stimulatory molecules . Diabetic nephropathy Introduction Type 2 diabetes mellitus (DM) is an increasingly prevalent metabolic disease in which the amount of insulin produced by the pancreas is inadequate to meet body needs. Type 2 DM has also been postulated as a disease of the innate immune system [1]. There is increasing evidence that an ongoing T-lymphocyte activation and cytokine-induced inflammatory response are closely related to the pathogenesis of type 2 DM and the associated complications such as cardiovascular disease and renal failure [1–3]. Inflammation and fibrosis are common disease mechanisms involved in many forms of progressive renal injury [1]. Diabetic nephropathy (DN) is a chronic kidney disease that develops as a result of the progression of DM. Our recent study have indicated that the enhanced inflammation in type 2 DM patients with DN is associated with the elevated plasma concentrations of inflammatory cytokines and chemokines, such as TNF-α, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10, and adiponectin, and differential activation of intracellular mitogen-activated protein kinases (MAPK) in different leukocytes such as T helper (Th) lymphocytes [3]. The inflammatory reaction is dependent on T cell help through cytokines and co-stimulatory molecules. The initi- ation of T cell activation requires a primary signal delivered by the antigenic peptide presented by major histocompati- bility complex (MHC) molecules and a non-specific signal generated by the interaction of co-stimulatory molecules [4, 5]. The co-stimulatory signal results from the interaction of CD28 on T cells with the B7 family B7–1 (CD80) and B7–2 (CD86) on antigen-presenting cells [6]. Resting antigen presenting cells are negative for CD80 and CD86 expression, but monocytes and dendritic cells constitutively express CD86 [7]. Expression of CD80 is mainly activation- induced [7]. Cytotoxic T-lymphocyte-associated antigen-4 J Clin Immunol (2008) 28:36–43 DOI 10.1007/s10875-007-9137-4 C. K. Wong : A. W. Y. Ho : C. W. K. Lam (*) Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong e-mail: waikeilam@cuhk.edu.hk P. C. Y. Tong : C. Y. Yeung : J. C. N. Chan : A. P. S. Kong Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong C. W. K. Lam Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology Foundation, Taipa, Macau