Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A
Alexander A. Merleev, Alina I. Marusina, Chelsea Ma, James T. Elder, Lam C. Tsoi, Siba P. Raychaudhuri, Stephan Weidinger, Elizabeth A. Wang, Iannis E. Adamopoulos, Guillaume Luxardi, Johann E. Gudjonsson, Michiko Shimoda, Emanual Maverakis
Alexander A. Merleev, Alina I. Marusina, Chelsea Ma, James T. Elder, Lam C. Tsoi, Siba P. Raychaudhuri, Stephan Weidinger, Elizabeth A. Wang, Iannis E. Adamopoulos, Guillaume Luxardi, Johann E. Gudjonsson, Michiko Shimoda, Emanual Maverakis
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Research Article Dermatology Genetics

Meta-analysis of RNA sequencing datasets reveals an association between TRAJ23, psoriasis, and IL-17A

Abstract

Numerous studies of relatively few patients have linked T cell receptor (TCR) genes to psoriasis but have yielded dramatically conflicting results. To resolve these discrepancies, we have chosen to mine RNA-Seq datasets for patterns of TCR gene segment usage in psoriasis. A meta-analysis of 3 existing and 1 unpublished datasets revealed a statistically significant link between the relative expression of TRAJ23 and psoriasis and the psoriasis-associated cytokine IL-17A. TRGV5, a TCR-γ segment, was also associated with psoriasis but correlated instead with IL-36A, other IL-36 family members, and IL-17C (not IL-17A). In contrast, TRAJ39 was strongly associated with healthy skin. T cell diversity measurements and analysis of CDR3 sequences were also conducted, revealing no psoriasis-associated public CDR3 sequences. Finally, in comparison with the expression of TCR-αβ genes, the expression of TCR-γδ genes was relatively low but mildly elevated in psoriatic skin. These results have implications for the development of targeted therapies for psoriasis and other autoimmune diseases. Also, the techniques employed in this study have applications in other fields, such as cancer immunology and infectious disease.

Authors

Alexander A. Merleev, Alina I. Marusina, Chelsea Ma, James T. Elder, Lam C. Tsoi, Siba P. Raychaudhuri, Stephan Weidinger, Elizabeth A. Wang, Iannis E. Adamopoulos, Guillaume Luxardi, Johann E. Gudjonsson, Michiko Shimoda, Emanual Maverakis

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Figure 5

Lack of HLA-C*06–specific TCR gene expression signature.

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Lack of HLA-C*06–specific TCR gene expression signature. (A) For psoriat...
(A) For psoriatic samples (Tsoi et al. dataset details [32] listed in Table 6), all the reads mapping to each TCR gene segment across HLA-C*06–positive versus all other HLA types in psoriatic individuals were pooled. The proportions for each TCR gene segment were calculated as described above. Fisher’s Exact test for count data was used to estimate statistically significant differences in the TCR segment usage. Gene segments with FDR < 0.05 and an odds ratio <0.5 or >2, are designated with an asterisk on the graph. Gene segments with statistically significant changes in their proportionate gene expression are listed in Supplemental Table 7. (B) For healthy individuals (Tsoi et al. dataset details [32] listed in Table 6), all reads mapping to each TCR gene segment across HLA-C*06–positive and all other HLA types were pooled separately. Fisher’s exact test for count data was used to estimate statistically significant differences in the TCR segment usage. Gene segments with FDR < 0.05 and an odds ratio <0.5 or >2 are designated with an asterisk on the graph. Gene segments with statistically significant changes in their proportionate gene expression are listed in Supplemental Table 8. (C and D) Analysis was repeated using the validation (Weidinger dataset details listed in Table 6) dataset for psoriasis HLA-C*06 versus all other HLA in C and for healthy control HLA-C*06 versus all other HLA in D.