IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Advances in Systems Biology Approaches for Autoimmune Diseases

  • Kim, Ho-Youn (Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center) ;
  • Kim, Hae-Rim (Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Lee, Sang-Heon (Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine)
  • Received : 2013.12.22
  • Accepted : 2014.04.10
  • Published : 2014.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.

Keywords

References

  1. Whitacre, C. C. 2001. Sex differences in autoimmune disease. Nat. Immunol. 2: 777-780. https://doi.org/10.1038/ni0901-777
  2. Blumberg, R. S., B. Dittel, D. Hafler, M. von Herrath, and F. O. Nestle. 2012. Unraveling the autoimmune translational research process layer by layer. Nat. Med. 18: 35-41. https://doi.org/10.1038/nm.2632
  3. Goldblatt, F. and S. G. O'Neill. 2013. Clinical aspects of autoimmune rheumatic diseases. Lancet 382: 797-808. https://doi.org/10.1016/S0140-6736(13)61499-3
  4. Trowsdale, J. 2011. The MHC, disease and selection. Immunol. Lett. 137: 1-8. https://doi.org/10.1016/j.imlet.2011.01.002
  5. Nocturne, G.. and X. Mariette. 2013. Advances in understanding the pathogenesis of primary Sjogren's syndrome. Nat. Rev. Rheumatol. 9: 544-556. https://doi.org/10.1038/nrrheum.2013.110
  6. Harley, J. B., A. L. Sestak, L. G. Willis, S. M. Fu, J. A. Hansen, and M. Reichlin. 1989. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 32: 826-836.
  7. Lessard, C. J., H. Li, I. Adrianto, J. A. Ice, A. Rasmussen, K. M. Grundahl, J. A. Kelly, M. G. Dozmorov, C. Miceli- Richard, S. Bowman, S. Lester, P. Eriksson, M. L. Eloranta, J. G. Brun, L. G. Gøransson, E. Harboe, J. M. Guthridge, K. M. Kaufman, M. Kvarnström, H. Jazebi, D. S. Cunninghame Graham, M. E. Grandits, A. N. Nazmul- Hossain, K. Patel, A. J. Adler, J. S. Maier-Moore, A. D. Farris, M. T. Brennan, J. A. Lessard, J. Chodosh, R. Gopalakrishnan, K. S. Hefner, G. D. Houston, A. J. Huang, P. J. Hughes, D. M. Lewis, L. Radfar, M. D. Rohrer, D. U. Stone, J. D. Wren, T. J. Vyse, P. M. Gaffney, J. A. James, R. Omdal, M. Wahren-Herlenius, G. G. Illei, T. Witte, R. Jonsson, M. Rischmueller, L. Rönnblom, G. Nordmark, W. F. Ng; UK Primary Sjögren's Syndrome Registry, X. Mariette, J. M. Anaya, N. L. Rhodus, B. M. Segal, R. H. Scofield, C. G. Montgomery, J. B. Harley, and K. L. Sivils. 2013. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome. Nat. Genet. 45: 1284-1292. https://doi.org/10.1038/ng.2792
  8. Viatte, S., D. Plant, and S. Raychaudhuri. 2013. Genetics and epigenetics of rheumatoid arthritis. Nat. Rev. Rheumatol. 9: 141-153. https://doi.org/10.1038/nrrheum.2012.237
  9. Zhebrun, D., Y. Kudryashova, A. Babenko, A. Maslyansky, N. Kunitskaya, D. Popcova, A. Klushina, E. Grineva, A. Kostareva, and E. Shlyakhto. 2011. Association of PTPN22 1858T/T genotype with type 1 diabetes, Graves' disease but not with rheumatoid arthritis in Russian population. Aging 3: 368-373. https://doi.org/10.18632/aging.100305
  10. Hewagama, A. and B. Richardson. 2009. The genetics and epigenetics of autoimmune diseases. J. Autoimmun. 33: 3-11. https://doi.org/10.1016/j.jaut.2009.03.007
  11. Franke, A., D. P. McGovern, J. C. Barrett, K. Wang, G. L. Radford-Smith, T. Ahmad, C. W. Lees, T. Balschun, J. Lee, R. Roberts, C. A. Anderson, J. C. Bis, S. Bumpstead, D. Ellinghaus, E. M. Festen, M. Georges, T. Green, T. Haritunians, L. Jostins, A. Latiano, C. G. Mathew, G. W. Montgomery, N. J. Prescott, S. Raychaudhuri, J. I. Rotter, P. Schumm, Y. Sharma, L. A. Simms, K. D. Taylor, D. Whiteman, C. Wijmenga, R. N. Baldassano, M. Barclay, T. M. Bayless, S. Brand, C. Büning, A. Cohen, J. F. Colombel, M. Cottone, L. Stronati, T. Denson, M. De Vos, R. D'Inca, M. Dubinsky, C. Edwards, T. Florin, D. Franchimont, R. Gearry, J. Glas, A. Van Gossum, S. L. Guthery, J. Halfvarson, H. W. Verspaget, J. P. Hugot, A. Karban, D. Laukens, I. Lawrance, M. Lemann, A. Levine, C. Libioulle, E. Louis, C. Mowat, W. Newman, J. Panés, A. Phillips, D. D. Proctor, M. Regueiro, R. Russell, P. Rutgeerts, J. Sanderson, M. Sans, F. Seibold, A. H. Steinhart, P. C. Stokkers, L. Torkvist, G. Kullak-Ublick, D. Wilson, T. Walters, S. R. Targan, S. R. Brant, J. D. Rioux, M. D'Amato, R. K. Weersma, S.Kugathasan, A. M. Griffiths, J. C. Mansfield, S. Vermeire, R. H. Duerr, M. S. Silverberg, J. Satsangi, S. Schreiber, J. H. Cho, V. Annese, H. Hakonarson, M. J. Daly, and M. Parkes. 2010. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42: 1118-1125. https://doi.org/10.1038/ng.717
  12. Oksenberg, J. R., S. E. Baranzini, S. Sawcer, and S. L. Hauser. 2008. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat. Rev. Genet. 9: 516-526. https://doi.org/10.1038/nrg2395
  13. Duffin, K. C., V. Chandran, D. D. Gladman, G. G. Krueger, J. T. Elder, and P. Rahman. 2008. Genetics of psoriasis and psoriatic arthritis: update and future direction. J. Rheumatol. 35: 1449-1453.
  14. Stahl, E. A., S. Raychaudhuri, E. F. Remmers, G. Xie, S. Eyre, B. P. Thomson, Y. Li, F. A. Kurreeman, A. Zhernakova, A. Hinks, C. Guiducci, R. Chen, L. Alfredsson, C. I. Amos, K. G. Ardlie; BIRAC Consortium, A. Barton, J. Bowes, E. Brouwer, N. P. Burtt, J. J. Catanese, J. Coblyn, M. J. Coenen, K. H. Costenbader, L. A. Criswell, J. B. Crusius, J. Cui, P. I. de Bakker, P. L. De Jager, B. Ding, P. Emery, E. Flynn, P. Harrison, L. J. Hocking, T. W. Huizinga, D. L. Kastner, X. Ke, A. T. Lee, X. Liu, P. Martin, A. W. Morgan, L. Padyukov, M. D. Posthumus, T. R. Radstake, D. M. Reid, M. Seielstad, M. F. Seldin, N. A. Shadick, S. Steer, P. P. Tak, W. Thomson, A. H. van der Helm-van Mil, I. E. van der Horst-Bruinsma, C. E. van der Schoot, P. L. van Riel, M. E. Weinblatt, A. G. Wilson, G. J. Wolbink, B. P. Wordsworth; YEAR Consortium, C. Wijmenga, E. W. Karlson, R. E. Toes, N. de Vries, A. B. Begovich, J. Worthington, K. A. Siminovitch, P. K. Gregersen, L. Klareskog, and Plenge. 2010. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat. Genet. 42: 508-514. https://doi.org/10.1038/ng.582
  15. Zhernakova, A., E. A. Stahl, G. Trynka, S. Raychaudhuri, E. A. Festen, L. Franke, H. J. Westra, R. S. Fehrmann, F. A. Kurreeman, B. Thomson, N. Gupta, J. Romanos, R. McManus, A. W. Ryan, G. Turner, E. Brouwer, M. D. Posthumus, E. F. Remmers, F. Tucci, R. Toes, E. Grandone, M. C. Mazzilli, A. Rybak, B. Cukrowska, M. J. Coenen, T. R. Radstake, P. L. van Riel, Y. Li, P. I. de Bakker, P. K. Gregersen, J. Worthington, K. A. Siminovitch, L. Klareskog, T. W. Huizinga, C. Wijmenga, and R. M. Plenge. 2011. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 7: e1002004. https://doi.org/10.1371/journal.pgen.1002004
  16. Han, J. W., H. F. Zheng, Y. Cui, L. D. Sun, D. Q. Ye, Z. Hu, J. H. Xu, Z. M. Cai, W. Huang, G. P. Zhao, H. F. Xie, H. Fang, Q. J. Lu, J. H. Xu, X. P. Li, Y. F. Pan, D. Q. Deng, F. Q. Zeng, Z. Z. Ye, X. Y. Zhang, Q. W. Wang, F. Hao, L. Ma, X. B. Zuo, F. S. Zhou, W. H. Du, Y. L. Cheng, J. Q. Yang, S. K. Shen, J. Li, Y. J. Sheng, X. X. Zuo, W. F. Zhu, F. Gao, P. L. Zhang, Q. Guo, B. Li, M. Gao, F. L. Xiao, C. Quan, C. Zhang, Z. Zhang, K. J. Zhu, Y. Li, D. Y. Hu, W. S. Lu, J. L. Huang, S. X. Liu, H. Li, Y. Q. Ren, Z. X. Wang, C. J. Yang, P. G. Wang, W. M. Zhou, Y. M. Lv, A. P. Zhang, S. Q. Zhang, D. Lin, Y. Li, H. Q. Low, M. Shen, Z. F. Zhai, Y. Wang, F. Y. Zhang, S. Yang, J. J. Liu, and X. J. Zhang. 2009. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat. Genet. 41: 1234-1237. https://doi.org/10.1038/ng.472
  17. Barrett, J. C., D. G. Clayton, P. Concannon, B. Akolkar, J. D. Cooper, H. A. Erlich, C. Julier, G. Morahan, J. Nerup, C. Nierras, V. Plagnol, F. Pociot, H. Schuilenburg, D. J. Smyth, H. Stevens, J. A. Todd, N. M. Walker, S. S. Rich, and Type 1 Diabetes Genetics Consortium. 2009. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41: 703-707. https://doi.org/10.1038/ng.381
  18. Hu, X., H. Kim, E. Stahl, R. Plenge, M. Daly, and S. Raychaudhuri. 2011. Integrating autoimmune risk loci with gene-expression data identifies specific pathogenic immune cell subsets. Am. J. Hum. Genet. 89: 496-506. https://doi.org/10.1016/j.ajhg.2011.09.002
  19. Ermann, J. and C. G. Fathman. 2001. Autoimmune diseases: genes, bugs and failed regulation. Nat. Immunol. 2: 759-761. https://doi.org/10.1038/ni0901-759
  20. Jaenisch, R. and A. Bird. 2003. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33 Suppl: 245-254. https://doi.org/10.1038/ng1089
  21. Jirtle, R. L. and M. K. Skinner. 2007. Environmental epigenomics and disease susceptibility. Nat. Rev. Genet. 8: 253-262. https://doi.org/10.1038/nrg2045
  22. Portela, A. and M. Esteller. 2010. Epigenetic modifications and human disease. Nat. Biotechnol. 28: 1057-1068. https://doi.org/10.1038/nbt.1685
  23. Sekigawa, I., M. Kawasaki, H. Ogasawara, K. Kaneda, H. Kaneko, Y. Takasaki, and H. Ogawa. 2006. DNA methylation: its contribution to systemic lupus erythematosus. Clin. Exp. Med. 6: 99-106. https://doi.org/10.1007/s10238-006-0103-x
  24. Quintero-Ronderos, P. and G. Montoya-Ortiz. 2012. Epigenetics and autoimmune diseases. Autoimmune Dis. 2012: 593720.
  25. Pauley, K. M., S. Cha, and E. K. Chan. 2009. MicroRNA in autoimmunity and autoimmune diseases. J. Autoimmun. 32: 189-194. https://doi.org/10.1016/j.jaut.2009.02.012
  26. Pascual, V., D. Chaussabel, and J. Banchereau. 2010. A genomic approach to human autoimmune diseases. Annu. Rev. Immunol. 28: 535-571. https://doi.org/10.1146/annurev-immunol-030409-101221
  27. Blanco, P., A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294: 1540-1543. https://doi.org/10.1126/science.1064890
  28. Shodell, M., K. Shah, and F. P. Siegal. 2003. Circulating human plasmacytoid dendritic cells are highly sensitive to corticosteroid administration. Lupus 12: 222-230. https://doi.org/10.1191/0961203303lu362xx
  29. Bennett, L., A. K. Palucka, E. Arce, V. Cantrell, J. Borvak, J. Banchereau, and V. Pascual. 2003. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 197: 711-723. https://doi.org/10.1084/jem.20021553
  30. Vincent, F. B., M. Northcott, A. Hoi, F. Mackay, and E. F. Morand EF. 2013. Clinical associations of serum interleukin- 17 in systemic lupus erythematosus. Arthritis Res. Ther. 15: R97. https://doi.org/10.1186/ar4277
  31. Krausgruber, T., K. Blazek, T. Smallie, S. Alzabin, H. Lockstone, N. Sahgal, T. Hussell, M. Feldmann, and I. A. Udalova. 2011. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Iimmunol. 12: 231-238. https://doi.org/10.1038/ni.1990
  32. Banchereau, J. and V. Pascual. 2006. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25: 383-392. https://doi.org/10.1016/j.immuni.2006.08.010
  33. Nikula, T., J. Mykkanen, O. Simell, and R. Lahesmaa. 2013. Genome-wide comparison of two RNA-stabilizing reagents for transcriptional profiling of peripheral blood. Transl. Res. 161: 181-188. https://doi.org/10.1016/j.trsl.2012.10.003
  34. Chiche, L., N. Jourde-Chiche, V. Pascual, and D. Chaussabel. 2013. Current perspectives on systems immunology approaches to rheumatic diseases. Arthritis Rheum. 65: 1407- 1417. https://doi.org/10.1002/art.37909
  35. Croze, E. 2010. Differential gene expression and translational approaches to identify biomarkers of interferon beta activity in multiple sclerosis. J. Interferon Cytokine Res. 30: 743-749. https://doi.org/10.1089/jir.2010.0022
  36. Mohr, S. and C. C. Liew. 2007. The peripheral-blood transcriptome: new insights into disease and risk assessment. Trends Mol. Med. 13: 422-432. https://doi.org/10.1016/j.molmed.2007.08.003
  37. Robinson, W. H., L. Steinman, and P. J. Utz. 2002. Proteomics technologies for the study of autoimmune disease. Arthritis Rheum. 46: 885-893. https://doi.org/10.1002/art.10129
  38. Baechler, E. C., F. M. Batliwalla, G. Karypis, P. M. Gaffney, W. A. Ortmann, K. J. Espe, K. B. Shark, W. J. Grande, K. M. Hughes, V. Kapur, P. K. Gregersen, and T. W. Behrens. 2003. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. USA 100: 2610-2615. https://doi.org/10.1073/pnas.0337679100
  39. Pascual, V., J. Banchereau, and A. K. Palucka. 2003. The central role of dendritic cells and interferon-alpha in SLE. Curr. Opin. Rheumatol. 15: 548-556. https://doi.org/10.1097/00002281-200309000-00005
  40. Sigurdsson, S., G. Nordmark, S. Garnier, E. Grundberg, T. Kwan, O. Nilsson, M. L. Eloranta, I. Gunnarsson, E. Svenungsson, G. Sturfelt, A. A. Bengtsson, A. Jonsen, L. Truedsson, S. Rantapaa-Dahlqvist, C. Eriksson, G. Alm, H. H. Goring, T. Pastinen, A. C. Syvanen, and L. Ronnblom. 2008. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum. Mol. Genet. 17: 2868-2876. https://doi.org/10.1093/hmg/ddn184
  41. Remmers, E. F., R. M. Plenge, A. T. Lee, R. R. Graham, G. Hom, T. W. Behrens, P. I. de Bakker, J. M. Le, H. S. Lee, F. Batliwalla, W. Li, S. L. Masters, M. G. Booty, J. P. Carulli, L. Padyukov, L. Alfredsson, L. Klareskog, W. V. Chen, C. I. Amos, L. A. Criswell, M. F. Seldin, D. L. Kastner, and P. K. Gregersen. 2007. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N. Engl. J. Med. 357: 977-986. https://doi.org/10.1056/NEJMoa073003
  42. Elkon, K. B. and V. V. Stone. 2011. Type I interferon and systemic lupus erythematosus. J. Interferon Cytokine Res. 31: 803-812. https://doi.org/10.1089/jir.2011.0045
  43. Stetson, D. B., J. S. Ko, T. Heidmann, and R. Medzhitov. 2008. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134: 587-598. https://doi.org/10.1016/j.cell.2008.06.032
  44. Bauer, J. W., M. Petri, F. M. Batliwalla, T. Koeuth, J. Wilson, C. Slattery, A. Panoskaltsis-Mortari, P. K. Gregersen, T. W. Behrens, and E. C. Baechler. 2009. Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum. 60: 3098- 3107. https://doi.org/10.1002/art.24803
  45. Tektonidou, M. G., M. M. Ward. 2010. Validity of clinical associations of biomarkers in translational research studies: the case of systemic autoimmune diseases. Arthritis Res. Ther. 12: R179. https://doi.org/10.1186/ar3143
  46. Kussmann, M., F. Raymond, M. Affolter. 2006. OMICS-driven biomarker discovery in nutrition and health. J. Biotechnol. 124: 758-787. https://doi.org/10.1016/j.jbiotec.2006.02.014
  47. Plebani, M., M. Pittoni, M. Celadin, D. Bernardi, and M. M. Mion. 2009. Recent advances in diagnostic technologies for autoimmune diseases. Autoimmun. Rev. 8: 238-243. https://doi.org/10.1016/j.autrev.2008.07.032
  48. Kussmann, M. and S. Blum. 2007. OMICS-derived targets for inflammatory gut disorders: opportunities for the development of nutrition related biomarkers. Endocr. Metab. Immune Disord. Drug Targets. 7: 271-287. https://doi.org/10.2174/187153007782794317
  49. Delaleu, N., H. Immervoll, J. Cornelius, and R. Jonsson. 2008. Biomarker profiles in serum and saliva of experimental Sjogren's syndrome: associations with specific autoimmune manifestations. Arthritis Res. Ther. 10: R22. https://doi.org/10.1186/ar2375
  50. Schweitzer, B., P. Predki, and M. Snyder. 2003. Microarrays to characterize protein interactions on a whole-proteome scale. Proteomics. 3: 2190-2199. https://doi.org/10.1002/pmic.200300610
  51. Ciofani, M., A. Madar, C. Galan, M. Sellars, K. Mace, F. Pauli, A. Agarwal, W. Huang, C. N. Parkurst, M. Muratet, K. M. Newberry, S. Meadows, A. Greenfield, Y. Yang, P. Jain, F. K. Kirigin, C. Birchmeier, E. F. Wagner, K. M. Murphy, R. M. Myers, R. Bonneau, and D. R. Littman. 2012. A validated regulatory network for Th17 cell specification. Cell 151: 289-303. https://doi.org/10.1016/j.cell.2012.09.016
  52. Ivanov, I. I., L. Zhou, and D. R. Littman. 2007. Transcriptional regulation of Th17 cell differentiation. Semin. Immunol. 19: 409-417. https://doi.org/10.1016/j.smim.2007.10.011
  53. Yosef, N., A. K. Shalek, J. T. Gaublomme, H. Jin, Y. Lee, A. Awasthi, C. Wu, K. Karwacz, S. Xiao, M. Jorgolli, D. Gennert, R. Satija, A. Shakya, D. Y. Lu, J. J. Trombetta, M. R. Pillai, P. J. Ratcliffe, M. L. Coleman, M. Bix, D. Tantin, H. Park, V. K. Kuchroo, and A. Regev. 2013. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496: 461-468. https://doi.org/10.1038/nature11981
  54. Solt, L. A., N. Kumar, P. Nuhant, Y. Wang, J. L. Lauer, J. Liu, M. A. Istrate, T. M. Kamenecka, W. R. Roush, D. Vidović, S. C. Schürer, J. Xu, G. Wagoner, P. D. Drew, P. R. Griffin, and T. P. Burris. 2011. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472: 491-494.
  55. Kitteringham, N. R., R. E. Jenkins, C. S. Lane, V. L. Elliott, and B. K. Park. 2009. Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 877: 1229- 1239. https://doi.org/10.1016/j.jchromb.2008.11.013
  56. Ghosh, D. and L. M. Poisson. 2009. "Omics" data and levels of evidence for biomarker discovery. Genomics 93: 13-16. https://doi.org/10.1016/j.ygeno.2008.07.006

Cited by

  1. Network-Based Approach for Analyzing Intra- and Interfluid Metabolite Associations in Human Blood, Urine, and Saliva vol.14, pp.2, 2014, https://doi.org/10.1021/pr501130a
  2. Candidate SNP Markers of Gender-Biased Autoimmune Complications of Monogenic Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters vol.7, pp.None, 2014, https://doi.org/10.3389/fimmu.2016.00130
  3. Plasmacytoid pre-dendritic cells (pDC): from molecular pathways to function and disease association vol.86, pp.None, 2019, https://doi.org/10.1016/j.semcdb.2018.02.014
  4. Nutrition and Rheumatoid Arthritis in the ‘Omics’ Era vol.13, pp.3, 2021, https://doi.org/10.3390/nu13030763
  5. A comprehensive database for integrated analysis of omics data in autoimmune diseases vol.22, pp.1, 2014, https://doi.org/10.1186/s12859-021-04268-4