AB0124 A novel c-type lectin receptor, clec16a, and systemic lupus erythematosus
Authors: R. C. Y. Tam, C. S. Lau, S. Yan, V. S. F. Chan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> C-type lectin receptors (CLR) are pattern recognition receptors that sense microbial pathogens and other forms of danger, leading to the induction of inflammatory responses in the host that link innate to adaptive immunity. Abnormalities in expression of CLRs can lead to various immune complications, such as autoimmune diseases. In several independent genome-wide association studies, polymorphisms of the C-type lectin domain family 16 member A (<i>CLEC16A</i>) gene were found to be associated with different autoimmune diseases, including systemic lupus erythematosus (SLE). Until now, two encoding isoforms of <i>CLEC16A</i> have been found in peripheral blood mononuclear cells (PBMC) in Caucasians, while none have been reported in Chinese. <h3>Methods</h3> <i>CLEC16A</i> expressed in Chinese PBMC is cloned and sequenced. To compare the expression levels of <i>CLEC16A</i> in normal versus SLE individuals, PBMC is collected from normal and SLE individuals for quantitative polymerase chain reaction analysis. <h3>Results</h3> Sequence differences have been found in both <i>CLEC16A</i> isoforms expressed in Chinese PBMC compared to Caucasians’: the entire exon 5 is consistently absent in isoforms 1 and 2, and an additional 54-bp deletion has been detected in isoform 2. It has also been observed that expressions of both isoforms 1 and 2 are significantly lower in SLE than in normal individuals (p=0.014 and p&lt;0.001 respectively; n=51 normal VS 129 SLE). Yet, their expression levels do not correlate with disease activity as measured by SLE disease activity index (SLEDAI), as patients grouped according to their SLEDAI have similar expressions of isoforms 1 and 2. <h3>Conclusions</h3> Additional isoforms of <i>CLEC16A</i> are expressed in Chinese PBMC, which differ from the ones reported. Further experiments will be performed to clone any other possible isoforms expressed in Chinese. From expression comparison study, results suggest SLE patients express lower levels of both isoforms 1 and 2 of CLEC16A in PBMC, but their expressions do not correlate with clinical disease activity. The molecular and cellular functions of CLEC16A are under investigation, which would shed light on the importance of this receptor in SLE. <h3>References</h3> Márquez, A. <i>et al.</i> Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15(−) Crohn’s disease patients. <i>European Journal of Human Genetics</i><b>17</b>, 1304-1308 (2009). Mero, I.-L. <i>et al.</i> Exploring the CLEC16A gene reveals a MS-associated variant with correlation to the relative expression of CLEC16A isoforms in thymus. <i>Genes and immunity</i><b>12</b>, 191-8 (2011). Todd, J. a <i>et al.</i> Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. <i>Nature genetics</i><b>39</b>, 857-64 (2007). Zhang, Z. <i>et al.</i> Polymorphisms at 16p13 are associated with systemic lupus erythematosus in the Chinese population. <i>Journal of medical genetics</i><b>48</b>, 69-72 (2010). <h3>Disclosure of Interest</h3> None Declared