AB0142 Sjögren's Syndrome-Associated Transcripts Show Correlation with Objective Measures of Dryness
Authors: J.A. Ice, I. Adrianto, A. Rasmussen, D.U. Stone, B.M. Segal, N.L. Rhodus, L. Radfar, C.G. Montgomery, R.H. Scofield, K.L. Sivils, C.J. Lessard
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Sjögren9s syndrome (SS) is a chronic autoimmune disorder in which exocrine dysfunction can lead to chronic, debilitating dryness. Expression studies in SS have identified the dysregulated expression of coding and non-coding transcripts enriched in innate and adaptive immune response pathways. <h3>Objectives</h3> In our recent SS RNA-seq study, we identified 3748 transcripts showing differential expression (DE; FC&gt;2 or &lt;0.5, q&lt;0.05) in SS patients compared to healthy controls. Of these SS-associated transcripts,[CL1] we sought to identify transcripts whose expression is significantly correlated with objective measures of dryness employed by the 2002 American-European Consensus Group (AECG) classification criteria of SS, including whole unstimulated salivary flow (WUSF), lissamine green (LG) staining, and Schirmer9s (Sch) tear migration. <h3>Methods</h3> Normalized expression data from a whole blood SS RNA-seq study was obtained for 57 cases and 11 healthy controls who underwent multidisciplinary clinical evaluation for the 2002 AECG classification criteria. Objective dryness measures (WUSF, LG, &amp; Sch) were normalized by log<sub>2</sub> transformation and correlation analysis (Spearman for WUSF and LG; Pearson for Sch) was performed for each clinical measure against all of 3748 DE transcripts. Both <i>r</i> or σ and a FDR-corrected <i>p</i>-value, or <i>q</i>-value, were calculated. Significantly correlated transcripts were defined by <i>q</i>&lt;0.05. <h3>Results</h3> For WUSF, the significant positive correlation between WUSF rate and the expression of 2 non-coding transcripts was observed: the small Cajal body-specific RNA 5 (<i>SCARNA5</i>; σ=0.50, <i>q</i>=0.018) and the uncharacterized antisense lncRNA RP11–137H2.4 (σ=0.50, <i>q</i>=0.018). For LG, positive correlation was observed for 31 transcripts (0.42&lt;σ&lt;0.51, 0.017&lt;<i>q</i>&lt;0.05) mostly represented by interferon-inducible (IFI) protein-coding genes (e.g. <i>IFIT3</i>, <i>OAS3</i>, and <i>IRF7)</i>, although for the pseudogene, <i>ZDHHC4P1</i>, and its neighboring IFI gene <i>EPSTI1</i> both showed significant positive correlation. For LG, the only negatively correlated transcript was the sodium bicarbonate transporter <i>SCL4A10</i> (σ= -0.43, <i>q</i>=0.045). For Sch, 3 transcripts (<i>CARD16</i>, <i>HMGB2</i>, and <i>BLC2A1</i>) were negatively correlated (-0.51&lt;σ&lt;-0.49, 0.018&lt;<i>q</i>&lt;0.019), while the transcript <i>IQCH</i> was positively correlated (σ=0.49, <i>q</i>=0.019). <h3>Conclusions</h3> We identified SS-associated transcripts whose expression correlates with clinical measures of dryness. For WUSF, the ncRNA <i>SCARNA5</i> is situated within an intron of the Crohn9s disease-associated gene autophagy-related 16-like 1 (<i>ATG16L1</i>). Although IFI genes have previously shown correlation with WUSF, the ZDHHC4P1 pseudogene could regulate neighboring SS-associated IFI gene <i>EPSTI1</i>. For Sch, <i>CARD16</i> is a caspase inhibitor that influences apoptotic responses that induces NF-kB activation in inflammation, while <i>BLC2A1</i> has been shown to slow apoptoic responses. Further transcript characterization will allow us to assess their potentialas biomarkers or surrogates of objective clinical measures for SS. <h3>Disclosure of Interest</h3> None declared