P181 KIR2DL3 protects the development of type 1 diabetes in children under 10 years old in South Indian population

Abstract

Aim Type 1 diabetes (T1D) is a multifactorial autoimmune disease that leads to the destruction of insulin producing β -cells of pancreas. Natural killer (NK) cells not only exert cytotoxic activity against tumor cells or infected cells but also act to regulate the function of other immune cells through cell contact-dependent mechanisms or secretion of cytokines and chemokines. Killer cell Ig-liker receptors (KIR) are key receptors of human NK cells. The aim of the present study is to identify if any association between KIR genes T1D. Methods Blood samples were collected from T1D patients (n = 112) with varied age of onset (0–10 yrs, n = 30; 10–20 yrs, n = 56; >20 years, n = 26) enrolled in Govt. Rajaji Hospital, Madurai, India along with their healthy siblings (n = 51) with due ethical clearance and consent. Genomic DNA was extracted and KIR genes were typed by duplex SSP method. Unusual KIR genotypes were further confirmed by One Lambda rSSO method. Comparisons were made by two-tailed Fisher’s exact probabilities (p), with p Results No difference was observed in the frequencies of any KIR genes between T1D and sibling controls (see figure). However, a significant decrease in the frequency of KIR2DL3 was observed in early onset patients of 0–10 years old compared to sibling controls (66.7% vs. 86.3%; P Conclusions The KIR2DL3 seems to be protective from developing T1D in young children. The protective NK cell activity may be mediated through weak inhibitory KIR2DL3 interactions (i.e., the lack of strong NK cell inhibition), perhaps in combination with one of the many conserved NK cell activating receptors. Further analyses of HLA ligands are necessary to substantiate this novel genetic association. Download high-res image (418KB) Download full-size image