Pediatric Diabetes 2012: 13: 147 – 154 doi: 10.1111/j.1399-5448.2011.00794.x All rights reserved 2011 John Wiley & Sons A/S Pediatric Diabetes Original Article Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria Ururahy MAG, Loureiro MB, Freire-Neto FP, Souza KSC, Zuhl I, Brand˜ ao-Neto J, Hirata RDC, Doi SQ, Arrais RF, Hirata MH, Almeida MG, Rezende AA. Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria. Pediatric Diabetes 2012: 13: 147 – 154. Objective: To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes. Design and methods: Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin -1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated. Results: DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1β, IL-6, and TNF-α were higher in DM1 and TLR2, IL-1β, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria. Conclusions: Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria. Marcela Abbott Galv ˜ ao Ururahy a , Melina Bezerra Loureiro a , Francisco Paulo Freire-Neto a , Karla Simone Costa de Souza a , Irina Zuhl b , Jos ´ e Brand ˜ ao-Neto c , Rosario Dominguez Crespo Hirata d , Sonia de Quateli Doi e , Ricardo Fernando Arrais f , Mario Hiroyuki Hirata d , Maria das Grac ¸ as Almeida a and Adriana Augusto de Rezende a a Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, RN 59012570, Brazil; b Center for Biologics Research and Evaluation, Food and Drug Administration, Rockville, MD 20852-1448, USA; c Department of Clinical Medicine, Federal University of Rio Grande do Norte, Natal, RN 59012570, Brazil; d Department of Clinical and Toxicological Analyses, University of S˜ ao Paulo, S ˜ ao Paulo, SP 05508900, Brazil; e Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; and f Department of Pediatrics, Federal University of Rio Grande do Norte, Natal, RN 59012570, Brazil Key words: inflammation – microalbuminuria – toll-like receptors – type 1 diabetes Corresponding author: Adriana A. de Rezende, Rua Pastor Gabino Brelaz, 1401, Bl:A, Apto: 101, Capim Macio, Natal, RN, CEP 59082-010, Brazil. Tel: +55 84 3207-2704; fax: +55 84 3342-9833; e-mail: adrirezende@ufrnet.br Submitted 25 February 2011. Accepted for publication 2 June 2011 147