Background/Purpose: Sjögren’s syndrome (SS) is an autoimmune disease characterized by autoantibodies to Ro and/or La proteins and lymphocytic infiltration into exocrine glands. Multiple sclerosis (MS) is an inflammatory and degenerative disorder of the central nervous system characterized by damage to the myelin sheath. Even though SS and MS have different clinical manifestations, genetic studies have suggested that the underlying etiology is common in both diseases. We used RNA-seq to compare the expression of (DE) protein-coding and non-coding transcripts in 15 MS patients to SS anti-Ro positive (n=27) and SS anti-Ro negative (n=30) patients as well as 27 healthy controls.

Methods: Whole blood RNA samples were isolated using the NuGEN Encore kit. Sequencing was performed using the Illumina HiSeq 2000. Raw FASTQ files were aligned to the human genome using Tophat. The read counts per transcript were generated using easyRNASeq in R. DE transcripts were determined using DESeq with a false discovery rate q-value of 0.05 and a fold change (FC) of >2 or <0.5.

Results: We observed 1638, 3324, and 4052 DE transcripts when comparing each group of SS anti-Ro positive, SS anti-Ro negative, and MS patients versus healthy controls, respectively. Relevant pathways from MS DE transcripts included synaptic transmission, nervous system development, and cell differentiation among others (P<0.0001) similar to those of SS anti-Ro negative patients. Using DE transcripts relevant to distinguish two groups of SS patients, we also found MS patients clustered together with SS anti-Ro negative patients in the principal components analysis plot. In addition, we observed the expression of interferon-inducible genes and the B-cell cytokine, APRIL, were significantly higher in SS anti-Ro positive patients compared to MS patients and to healthy controls (P<0.01).

Conclusion: Our analysis shows that RNA profiles of MS patients are more similar to SS anti-Ro negative patients than the SS anti-Ro positive patients. This suggests that MS treatments may be beneficial for SS anti-Ro negative patients. Furthermore, these data have identified several putative DE in both coding and lncRNA regions in SS and MS. Further comparisons of different SS and MS subtypes are needed to confirm and expand these findings.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rna-sequencing-reveals-sjogrens-syndrome-anti-ro-negative-patients-share-similar-pathways-to-multiple-sclerosis-patients/