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1.  B-Cell and Monocyte Contribution to Systemic Lupus Erythematosus Identified by Cell-Type-Specific Differential Expression Analysis in RNA-Seq Data 
Bioinformatics and Biology Insights  2015;9(Suppl 3):11-19.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by complex interplay among immune cell types. SLE activity is experimentally assessed by several blood tests, including gene expression profiling of heterogeneous populations of cells in peripheral blood. To better understand the contribution of different cell types in SLE pathogenesis, we applied the two methods in cell-type-specific differential expression analysis, csSAM and DSection, to identify cell-type-specific gene expression differences in heterogeneous gene expression measures obtained using RNA-seq technology. We identified B-cell-, monocyte-, and neutrophil-specific gene expression differences. Immunoglobulin-coding gene expression was altered in B-cells, while a ribosomal signature was prominent in monocytes. On the contrary, genes differentially expressed in the heterogeneous mixture of cells did not show any functional enrichment. Our results identify antigen binding and structural constituents of ribosomes as functions altered by B-cell- and monocyte-specific gene expression differences, respectively. Finally, these results position both csSAM and DSection methods as viable techniques for cell-type-specific differential expression analysis, which may help uncover pathogenic, cell-type-specific processes in SLE.
doi:10.4137/BBI.S29470
PMCID: PMC4599594  PMID: 26512198
cell-type-specific; deconvolution; RNA-seq; SLE; csSAM; DSection
2.  Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus 
Annals of the rheumatic diseases  2011;70(9):1569-1574.
Objectives
Vitamin D deficiency is widespread and has been associated with many chronic diseases, including autoimmune disorders. A study was undertaken to explore the impact of low vitamin D levels on autoantibody production in healthy individuals, as well as B cell hyperactivity and interferon α (IFNα) activity in patients with systemic lupus erythematosus (SLE).
Methods
Serum samples from 32 European American female patients with SLE and 32 matched controls were tested for 25-hydroxyvitamin D (25(OH)D) levels, lupus-associated autoantibodies and serum IFNα activity. Isolated peripheral blood mononuclear cells were tested for intracellular phospho-ERK 1/2 as a measure of B cell activation status.
Results
Vitamin D deficiency (25(OH)D <20 ng/ml) was significantly more frequent among patients with SLE (n=32, 69%) and antinuclear antibody (ANA)-positive controls (n=14, 71%) compared with ANA-negative controls (n=18, 22%) (OR 7.7, 95% CI 2.0 to 29.4, p=0.003 and OR 8.8, 95% CI 1.8 to 43.6, p=0.011, respectively). Patients with high B cell activation had lower mean (SD) 25(OH)D levels than patients with low B cell activation (17.2 (5.1) vs 24.2 (3.9) ng/ml; p=0.009). Patients with vitamin D deficiency also had higher mean (SD) serum IFNα activity than patients without vitamin D deficiency (3.5 (6.6) vs 0.3 (0.3); p=0.02).
Conclusions
The observation that ANA-positive healthy controls are significantly more likely to be deficient in vitamin D than ANA-negative healthy controls, together with the finding that vitamin D deficiency is associated with certain immune abnormalities in SLE, suggests that vitamin D plays an important role in autoantibody production and SLE pathogenesis.
doi:10.1136/ard.2010.148494
PMCID: PMC3149865  PMID: 21586442
3.  Genetic Associations of LYN with Systemic Lupus Erythematosus 
Genes and immunity  2009;10(5):397-403.
We targeted LYN, a src-tyosine kinase involved in B cell activation, in case-control association studies using populations of European American, African American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, demonstrates significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (p=1.1 × 10−4, OR=0.81 (95% CI: 0.73 – 0.90)). This SNP is located in the 5′ UTR within the first intron near the transcription initiation site of LYN. Additional SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for SLE susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European American female cases by ACR classification criteria reveals a reduction in the risk of hematologic disorder with rs6983130 compared to cases without hematologic disorders (p=1.5 × 10−3, OR=0.75 (95% C.I.=0.62-0.89)). None of the 90 SNPs tested demonstrate significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
doi:10.1038/gene.2009.19
PMCID: PMC2750001  PMID: 19369946
systemic lupus erythematosus; association; LYN; SNP

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