About this Journal Submit a Manuscript Table of Contents
Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 582352, 15 pages
http://dx.doi.org/10.1155/2012/582352
Review Article

Genetics of SLE: Functional Relevance for Monocytes/Macrophages in Disease

Molecular and Cellular Therapeutics and RCSI Research Institute, Royal College of Surgeons in Ireland, Dublin 2, Ireland

Received 23 June 2012; Revised 24 August 2012; Accepted 25 September 2012

Academic Editor: Timothy B. Niewold

Copyright © 2012 Jennifer C. Byrne et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. G. Helmick, D. T. Felson, R. C. Lawrence et al., “Estimates of the prevalence of arthritis and other rheumatic conditions in the United States—part I,” Arthritis & Rheumatism, vol. 58, no. 1, pp. 15–25, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. S. L. Peng, “Altered T and B lymphocyte signaling pathways in lupus,” Autoimmunity Reviews, vol. 8, no. 3, pp. 179–183, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Kavai and G. Szegedi, “Immune complex clearance by monocytes and macrophages in systemic Lupus erythematosus,” Autoimmunity Reviews, vol. 6, no. 7, pp. 497–502, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Rönnblom, M. L. Eloranta, and G. V. Alm, “The type I interferon system in systemic Lupus erythematosus,” Arthritis & Rheumatism, vol. 54, no. 2, pp. 408–420, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. A. L. Sestak, B. G. Fürnrohr, J. B. Harley, J. T. Merrill, and B. Namjou, “The genetics of systemic Lupus erythematosus and implications for targeted therapy,” Annals of the Rheumatic Diseases, vol. 70, no. 1, supplement, pp. i37–i43, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. K. A. Davies, J. A. Schifferli, and M. J. Walport, “Complement deficiency and immune complex disease,” Springer Seminars in Immunopathology, vol. 15, no. 4, pp. 397–416, 1994. View at Scopus
  7. L. C. Korb and J. M. Ahearn, “C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic Lupus erythematosus revisited,” Journal of Immunology, vol. 158, no. 10, pp. 4525–4528, 1997. View at Scopus
  8. M. C. Pickering and M. J. Walport, “Links between complement abnormalities and systemic Lupus erythematosus,” Rheumatology, vol. 39, no. 2, pp. 133–141, 2000. View at Scopus
  9. P. S. Patole, H. J. Gröne, S. Segerer et al., “Viral double-stranded RNA aggravates lupus nephritis through toll-like receptor 3 on glomerular mesangial cells and antigen-presenting cells,” Journal of the American Society of Nephrology, vol. 16, no. 5, pp. 1326–1338, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. P. Y. Lee, Y. Kumagai, Y. Li et al., “TLR7-dependent and FcγR-independent production of type I interferon in experimental mouse lupus,” Journal of Experimental Medicine, vol. 205, no. 13, pp. 2995–3006, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. S. R. Christensen, M. Kashgarian, L. Alexopoulou, R. A. Flavell, S. Akira, and M. J. Shlomchik, “Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus,” Journal of Experimental Medicine, vol. 202, no. 2, pp. 321–331, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. B. Namjou, C. B. Choi, I. T. Harley, et al., “Evaluation of TRAF6 in a large multiancestral lupus cohort,” Arthritis & Rheumatism, vol. 64, no. 6, pp. 1960–1969, 2012.
  13. S. Sigurdsson, G. Nordmark, H. H. H. Göring et al., “Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic Lupus erythematosus,” American Journal of Human Genetics, vol. 76, no. 3, pp. 528–537, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. M. C. Dall'Era, P. M. Cardarelli, B. T. Preston, A. Witte, and J. C. Davis, “Type I interferon correlates with serological and clinical manifestations of SLE,” Annals of the Rheumatic Diseases, vol. 64, no. 12, pp. 1692–1697, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Hashimoto, K. Hirota, H. Yoshitomi et al., “Complement drives Th17 cell differentiation and triggers autoimmune arthritis,” Journal of Experimental Medicine, vol. 207, no. 6, pp. 1135–1143, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Zhang, S. Liu, Y. Yu et al., “Immune complex enhances tolerogenecity of immature dendritic cells via FcγRIIb and promotes FcγRIIb-overexpressing dendritic cells to attenuate lupus,” European Journal of Immunology, vol. 41, no. 4, pp. 1154–1164, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Topaloglu, A. Bakkaloglu, J. H. Slingsby et al., “Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family,” Kidney International, vol. 50, no. 2, pp. 635–642, 1996. View at Scopus
  18. F. Petry, “Molecular basis of hereditary C1q deficiency,” Immunobiology, vol. 199, no. 2, pp. 286–294, 1998. View at Scopus
  19. M. Loos and H. P. Heinz, “Component deficiencies—1. The first component: C1q, C1r, C1s,” Progress in Allergy, vol. 39, pp. 212–231, 1986. View at Scopus
  20. A. Chevailler, C. Drouet, D. Ponard et al., “Non-coordinated biosynthesis of early complement components in a deficiency of complement proteins C1r and C1s,” Scandinavian Journal of Immunology, vol. 40, no. 4, pp. 383–388, 1994. View at Publisher · View at Google Scholar · View at Scopus
  21. M. I. Zervou, V. M. Vazgiourakis, N. Yilmaz, et al., “TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey,” Human Immunology, vol. 72, no. 12, pp. 1210–1213, 2011.
  22. B. P. Morgan and M. J. Walport, “Complement deficiency and disease,” Immunology Today, vol. 12, no. 9, pp. 301–306, 1991. View at Scopus
  23. Y. L. Wu, G. Hauptmann, M. Viguier, and C. Y. Yu, “Molecular basis of complete complement C4 deficiency in two North-African families with systemic Lupus erythematosus,” Genes and Immunity, vol. 10, no. 5, pp. 433–445, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Yang, E. K. Chung, B. Zhou et al., “The intricate role of complement component C4 in human systemic Lupus erythematosus,” Current Directions in Autoimmunity, vol. 7, pp. 98–132, 2004. View at Scopus
  25. N. Shen, Q. Fu, Y. Deng, et al., “Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic Lupus erythematosus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 36, pp. 15838–15843, 2010.
  26. A. Kawasaki, H. Furukawa, Y. Kondo et al., “TLR7 single-nucleotide polymorphisms in the 3' untranslated region and intron 2 independently contribute to systemic Lupus erythematosus in Japanese women: a case-control association study,” Arthritis Research and Therapy, vol. 13, no. 2, article R41, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. B. P. dos Santos, J. V. Valverde, P. Rohr, et al., “TLR7/8/9 polymorphisms and their associations in systemic Lupus erythematosus patients from southern Brazil,” Lupus, vol. 21, no. 3, pp. 302–309, 2012.
  28. K. Tao, M. Fujii, S. I. Tsukumo et al., “Genetic variations of Toll-like receptor 9 predispose to systemic Lupus erythematosus in Japanese population,” Annals of the Rheumatic Diseases, vol. 66, no. 7, pp. 905–909, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. C. J. Xu, W. H. Zhang, H. F. Pan, X. P. Li, J. H. Xu, and D. Q. Ye, “Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic Lupus erythematosus among Chinese,” Molecular Biology Reports, vol. 36, no. 8, pp. 2245–2248, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. Q. Fu, J. Zhao, X. Qian et al., “Association of a functional IRF7 variant with systemic Lupus erythematosus,” Arthritis & Rheumatism, vol. 63, no. 3, pp. 749–754, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. S. L. Musone, K. E. Taylor, T. T. Lu et al., “Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic Lupus erythematosus,” Nature Genetics, vol. 40, no. 9, pp. 1062–1064, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Fan, J. H. Tao, L. P. Zhang, L. H. Li, and D. Q. Ye, “The association between BANK1 and TNFAIP3 gene polymorphisms and systemic Lupus erythematosus: a meta-analysis,” International Journal of Immunogenetics, vol. 38, no. 2, pp. 151–159, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Q. Cai, Z. X. Wang, W. S. Lu et al., “A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic Lupus erythematosus in Chinese Han population,” Molecular Biology Reports, vol. 37, no. 1, pp. 389–394, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. J. S. Bates, C. J. Lessard, J. M. Leon et al., “Meta-analysis and imputation identifies a 109kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations,” Genes and Immunity, vol. 10, no. 5, pp. 470–477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. J. W. Han, H. F. Zheng, Y. Cui, et al., “Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic Lupus erythematosus,” Nature Genetics, vol. 41, no. 11, pp. 1234–1237, 2009.
  36. V. Gateva, J. K. Sandling, G. Hom et al., “A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic Lupus erythematosus,” Nature Genetics, vol. 41, no. 11, pp. 1228–1233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Hellquist, J. K. Sandling, M. Zucchelli et al., “Variation in STAT4 is associated with systemic Lupus erythematosus in a Finnish family cohort,” Annals of the Rheumatic Diseases, vol. 69, no. 5, pp. 883–886, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. H. Yuan, F. Jin-Bao, P. Hai-Feng, et al., “A meta-analysis of the association of STAT4 polymorphism with systemic Lupus erythematosus,” Modern Rheumatology, vol. 20, no. 3, pp. 257–262, 2010.
  39. P. Li, C. Cao, H. Luan et al., “Association of genetic variations in the STAT4 and IRF7/KIAA1542 regions with systemic Lupus erythematosus in a Northern Han Chinese population,” Human Immunology, vol. 72, no. 3, pp. 249–255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Sigurdsson, G. Nordmark, S. Garnier et al., “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,” Human Molecular Genetics, vol. 17, no. 18, pp. 2868–2876, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. D. S. Cunninghame Graham, D. L. Morris, T. R. Bhangale, et al., “Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic Lupus erythematosus,” PLoS Genet, vol. 7, no. 10, Article ID e1002341, 2011.
  42. D. S. C. Graham, M. Akil, and T. J. Vyse, “Association of polymorphisms across the tyrosine kinase gene, TYK2 in UK SLE families,” Rheumatology, vol. 46, no. 6, pp. 927–930, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. I. Ferreiro-Neira, M. Calaza, E. Alonso-Perez et al., “Opposed independent effects and epistasis in the complex association of IRF5 to SLE,” Genes and Immunity, vol. 8, no. 5, pp. 429–438, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. P. R. Taylor, A. Carugati, V. A. Fadok et al., “A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo,” Journal of Experimental Medicine, vol. 192, no. 3, pp. 359–366, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. D. M. Santer, A. E. Wiedeman, T. H. Teal, P. Ghosh, and K. B. Elkon, “Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes,” Journal of Immunology, vol. 188, no. 2, pp. 902–915, 2012.
  46. D. M. Santer, B. E. Hall, T. C. George et al., “C1q deficiency leads to the defective suppression of IFN-α in response to nucleoprotein containing immune complexes,” Journal of Immunology, vol. 185, no. 8, pp. 4738–4749, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. M. C. Pickering, M. Botto, P. R. Taylor, P. J. Lachmann, and M. J. Walport, “Systemic Lupus erythematosus, complement deficiency, and apoptosis,” Advances in Immunology, vol. 76, pp. 227–324, 2000. View at Scopus
  48. M. J. Walport, K. A. Davies, and M. Botto, “C1q and systemic Lupus erythematosus,” Immunobiology, vol. 199, no. 2, pp. 265–285, 1998. View at Scopus
  49. C. H. Chew, K. H. Chua, L. H. Lian, S. M. Puah, and S. Y. Tan, “PCR-RFLP genotyping of C1q mutations and single nucleotide polymorphisms in Malaysian patients with systemic Lupus erythematosus,” Human Biology, vol. 80, no. 1, pp. 83–93, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. C. Yung Yu, E. K. Chung, Y. Yang et al., “Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex,” Progress in Nucleic Acid Research and Molecular Biology, vol. 75, pp. 217–292, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. J. A. Schifferli, G. Hauptmann, and J. P. Paccaud, “Complement-mediated adherence of immune complexes to human erythrocytes. Difference in the requirements for C4A and C4B,” FEBS Letters, vol. 213, no. 2, pp. 415–418, 1987. View at Scopus
  52. L. Boteva, D. L. Morris, J. Cortés-Hernández, J. Martin, T. J. Vyse, and M. M. Fernando, “Genetically determined partial complement C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations,” The American Journal of Human Genetics, vol. 90, no. 3, pp. 445–456, 2012.
  53. Y. Yang, E. K. Chung, L. W. Yee et al., “Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic Lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans,” American Journal of Human Genetics, vol. 80, no. 6, pp. 1037–1054, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. T. Takai, “Roles of Fc receptors in autoimmunity,” Nat Rev Immunol, vol. 2, no. 8, pp. 580–592, 2002.
  55. F. Nimmerjahn, “Activating and inhibitory FcγRs in autoimmune disorders,” Springer Seminars in Immunopathology, vol. 28, no. 4, pp. 305–319, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Sondermann, J. Kaiser, and U. Jacob, “Molecular basis for immune complex recognition: a comparison of Fc-receptor structures,” Journal of Molecular Biology, vol. 309, no. 3, pp. 737–749, 2001. View at Publisher · View at Google Scholar · View at Scopus
  57. J. L. Ceuppens, M. L. Baroja, F. Van Vaeck, and C. L. Anderson, “Defect in the membrane expression of high affinity 72-kD Fc γ receptors on phagocytic cells in four healthy subjects,” Journal of Clinical Investigation, vol. 82, no. 2, pp. 571–578, 1988. View at Scopus
  58. H. M. Dijstelbloem, C. G. M. Kallenberg, and J. G. J. Van De Winkel, “Inflammation in autoimmunity: receptors for IgG revisited,” Trends in Immunology, vol. 22, no. 9, pp. 510–516, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. P. A. M. Warmerdam, J. G. J. Van de Winkel, A. Vlug, N. A. C. Westerdaal, and P. J. A. Capel, “A single amino acid in the second Ig-like domain of the human Fcγ receptor II is critical for human IgG2 binding,” Journal of Immunology, vol. 147, no. 4, pp. 1338–1343, 1991. View at Scopus
  60. A. P. Bazilio, V. S. T. Viana, R. Toledo, V. Woronik, E. Bonfá, and R. C. Monteiro, “FcγRIIa polymorphismml: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients,” Nephrology Dialysis Transplantation, vol. 19, no. 6, pp. 1427–1431, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. F. B. Karassa, T. A. Trikalinos, and J. P. A. Ioannidis, “Role of the Fcγ receptor IIa polymorphism in susceptibility to systemic Lupus erythematosus and lupus nephritis: a meta-analysis,” Arthritis & Rheumatism, vol. 46, no. 6, pp. 1563–1571, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. S. N. Yap, M. E. Phipps, M. Manivasagar, S. Y. Tan, and J. J. Bosco, “Human Fc gamma receptor IIA (FcγRIIA) genotyping and association with systemic Lupus erythematosus (SLE) in Chinese and Malays in Malaysia,” Lupus, vol. 8, no. 4, pp. 305–310, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. F. B. Karassa, T. A. Trikalinos, J. P. A. Ioannidis et al., “The FcγRIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis,” Kidney International, vol. 63, no. 4, pp. 1475–1482, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Kyogoku, H. M. Dijstelbloem, N. Tsuchiya et al., “Fcγ receptor gene polymorphisms in Japanese patients with systemic Lupus erythematosus: contribution of FCGR2B to genetic susceptibility,” Arthritis & Rheumatism, vol. 46, no. 5, pp. 1242–1254, 2002. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. T. Chu, N. Tsuchiya, C. Kyogoku et al., “Association of Fcγ receptor IIb polymorphism with susceptibility to systemic Lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations,” Tissue Antigens, vol. 63, no. 1, pp. 21–27, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. H. R. Koene, M. Kleijer, D. Roos, M. De Haas, and A. E. G. K. Von Dem Borne, “FcγRIIIB gene duplication: evidence for presence and expression of three distinct FcγRIIIB genes in NA(1+,2+)SH(+) individuals,” Blood, vol. 91, no. 2, pp. 673–679, 1998. View at Scopus
  67. R. G. M. Bredius, C. A. P. Fijen, M. De Haas et al., “Role of neutrophil FcγRIIa (CD32) and FcγRIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes,” Immunology, vol. 83, no. 4, pp. 624–630, 1994. View at Scopus
  68. H. M. Dijstelbloem, M. Bijl, R. Fijnheer, et al., “Fcgamma receptor polymorphisms in systemic Lupus erythematosus: association with disease and in vivo clearance of immune complexes,” Arthritis & Rheumatism, vol. 43, no. 12, pp. 2793–2800, 2000.
  69. Y. Hatta, N. Tsuchiya, J. Ohashi et al., “Association of Fcγ receptor IIIB, but not of Fcγ receptor IIA and IIIA, polymorphisms with systemic Lupus erythematosus in Japanese,” Genes and Immunity, vol. 1, no. 1, pp. 53–60, 1999. View at Scopus
  70. U. Siriboonrit, N. Tsuchiya, M. Sirikong et al., “Association of Fcγ receptor IIb and IIIb polymorphisms with susceptibility to systemic Lupus erythematosus in Thais,” Tissue Antigens, vol. 61, no. 5, pp. 374–383, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. C. H. Hong, “The association between fcgammaRIIIB polymorphisms and systemic Lupus erythematosus in Korea,” Lupus, vol. 14, no. 5, pp. 346–350, 2005.
  72. S. Bolland and J. V. Ravetch, “Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis,” Immunity, vol. 13, no. 2, pp. 277–285, 2000. View at Scopus
  73. T. L. McGaha, B. Sorrentino, and J. V. Ravetch, “Restoration of tolerance in lupus by targeted inhibitory receptor expression,” Science, vol. 307, no. 5709, pp. 590–593, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Mackay, A. Stanevsky, and T. Wang, “Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE,” Journal of Experimental Medicine, vol. 203, no. 9, pp. 2157–2164, 2006.
  75. R. A. Floto, “Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts,” Nature Medicine, vol. 11, no. 10, pp. 1056–1058, 2005.
  76. J. Bernet, J. Mullick, A. K. Singh, and A. Sahu, “Viral mimicry of the complement system,” Journal of Biosciences, vol. 28, no. 3, pp. 249–264, 2003. View at Scopus
  77. G. Hom, R. R. Graham, B. Modrek et al., “Association of systemic Lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX,” New England Journal of Medicine, vol. 358, no. 9, pp. 900–909, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. J. B. Harley, M. E. Alarcón-Riquelme, L. A. Criswell et al., “Genome-wide association scan in women with systemic Lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci,” Nature Genetics, vol. 40, no. 2, pp. 204–210, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. S. K. Nath, S. Han, X. Kim-Howard et al., “A nonsynonymous functional variant in integrin-αM (encoded by ITGAM) is associated with systemic Lupus erythematosus,” Nature Genetics, vol. 40, no. 2, pp. 152–154, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. B. Rhodes, et al., “The rs1143679 (R77H) lupus associated variant of ITGAM (CD11b) impairs complement receptor 3 mediated functions in human monocytes,” Annals of the Rheumatic Diseases, 2012. In press.
  81. T. Kawai and S. Akira, “The role of pattern-recognition receptors in innate immunity: update on toll-like receptors,” Nature Immunology, vol. 11, no. 5, pp. 373–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. D. H. Kono, M. K. Haraldsson, B. R. Lawson et al., “Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 29, pp. 12061–12066, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. D. C. Kang, R. V. Gopalkrishnan, Q. Wu, E. Jankowsky, A. M. Pyle, and P. B. Fisher, “mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 2, pp. 637–642, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. I. Kimkong, Y. Avihingsanon, and N. Hirankarn, “Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR,” Lupus, vol. 18, no. 12, pp. 1066–1072, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. K. Yasuda, C. Richez, J. W. Maciaszek et al., “Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes Is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production,” Journal of Immunology, vol. 178, no. 11, pp. 6876–6885, 2007. View at Scopus
  86. I. R. Rifkin, E. A. Leadbetter, L. Busconi, G. Viglianti, and A. Marshak-Rothstein, “Toll-like receptors, endogenous ligands, and systemic autoimmune disease,” Immunological Reviews, vol. 204, pp. 27–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. T. Lövgren, M. L. Eloranta, B. Kastner, M. Wahren-Herlenius, G. V. Alm, and L. Rönnblom, “Induction of interferon-α by immune complexes or liposomes containing systemic Lupus erythematosus autoantigen-and Sjögren's syndrome auto antigen-associated RNA,” Arthritis & Rheumatism, vol. 54, no. 6, pp. 1917–1927, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. P. Y. Lee, J. S. Weinstein, D. C. Nacionales et al., “A novel type i IFN-producing cell subset in murine lupus,” Journal of Immunology, vol. 180, no. 7, pp. 5101–5108, 2008. View at Scopus
  89. D. Feng, R. C. Stone, M. L. Eloranta et al., “Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic Lupus erythematosus,” Arthritis & Rheumatism, vol. 62, no. 2, pp. 562–573, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. G. Obermoser, “Lupus erythematosus and the skin: a journey at times perplexing, usually complex, often challenging, and evermore exhilarating,” Lupus, vol. 19, no. 9, pp. 1009–1011, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. L. Rönnblom, G. V. Alm, and M. L. Eloranta, “The type I interferon system in the development of lupus,” Seminars in Immunology, vol. 23, no. 2, pp. 113–121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. M. K. Crow, “Type I interferon in organ-targeted autoimmune and inflammatory diseases,” Arthritis Research & Therapy, vol. 12, p. S5, 2010. View at Scopus
  93. E. C. Baechler, F. M. Batliwalla, G. Karypis et al., “Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 5, pp. 2610–2615, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. S. V. Kozyrev and M. E. Alarcon-Riquelme, “The genetics and biology of Irf5-mediated signaling in lupus,” Autoimmunity, vol. 40, no. 8, pp. 591–601, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Smith, J. N. Gabhann, R. Higgs, et al., “Enhanced interferon regulatory factor 3 binding to the interleukin-23p19 promoter correlates with enhanced interleukin-23 expression in systemic Lupus erythematosus,” Arthritis & Rheumatism, vol. 64, no. 5, pp. 1601–1609, 2012.
  96. R. C. Stone, “Interferon regulatory factor 5 activation in monocytes of systemic Lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons,” Arthritis & Rheumatism, vol. 64, no. 3, pp. 788–798, 2012.
  97. R. R. Graham, C. Kyogoku, S. Sigurdsson et al., “Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 16, pp. 6758–6763, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. S. R. Christensen, J. Shupe, K. Nickerson, M. Kashgarian, R. Flavell, and M. J. Shlomchik, “Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of Lupus,” Immunity, vol. 25, no. 3, pp. 417–428, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Pisitkun, J. A. Deane, M. J. Difilippantonio, T. Tarasenko, A. B. Satterthwaite, and S. Bolland, “Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication,” Science, vol. 312, no. 5780, pp. 1669–1672, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. S. Subramanian, K. Tus, Q. Z. Li et al., “A Tlr7 translocation accelerates systemic autoimmunity in murine lupus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 26, pp. 9970–9975, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. J. A. Deane, P. Pisitkun, R. S. Barrett et al., “Control of Toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation,” Immunity, vol. 27, no. 5, pp. 801–810, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Deng, J. Zhao, W. Tan, et al., “Association of variants in the TLR7-TLR8 region with systemic Lupus erythematosus in non-asian populations,” Arthritis & Rheumatism, vol. 62, supplement 10, p. 1584, 2010.
  103. E. Sánchez, J. L. Callejas-Rubio, J. M. Sabio, et al., “Investigation of TLR5 and TLR7 as candidate genes for susceptibility to systemic Lupus erythematosus,” Clinical and Experimental Rheumatology, vol. 27, no. 2, pp. 267–271, 2009.
  104. H. García-Ortiz, R. Velázquez-Cruz, F. Espinosa-Rosales, S. Jiménez-Morales, V. Baca, and L. Orozco, “Association of TLR7 copy number variation with susceptibility to childhood-onset systemic Lupus erythematosus in Mexican population,” Annals of the Rheumatic Diseases, vol. 69, no. 10, pp. 1861–1865, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. E. D. Papadimitraki, C. Choulaki, E. Koutala et al., “Expansion of toll-like receptor 9-expressing B cells in active systemic Lupus erythematosus: implications for the induction and maintenance of the autoimmune process,” Arthritis & Rheumatism, vol. 54, no. 11, pp. 3601–3611, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. X. Wu and S. L. Peng, “Toll-like receptor 9 signaling protects against murine lupus,” Arthritis & Rheumatism, vol. 54, no. 1, pp. 336–342, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. M. W. Ng, C. S. Lau, T. M. Chan, W. H. S. Wong, and Y. L. Lau, “Polymorphisms of the toll-like receptor 9 (TLR9) gene with systemic Lupus erythematosus in Chinese [1],” Rheumatology, vol. 44, no. 11, pp. 1456–1457, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. F. Y. K. Demirci, S. Manzi, R. Ramsey-Goldman et al., “Association study of Toll-like Receptor 5 (TLR5) and Toll-like Receptor 9 (TLR9) polymorphisms in systemic Lupus erythematosus,” Journal of Rheumatology, vol. 34, no. 8, pp. 1708–1711, 2007. View at Scopus
  109. D. Ganguly, G. Chamilos, R. Lande et al., “Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8,” Journal of Experimental Medicine, vol. 206, no. 9, pp. 1983–1994, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. M. S. Lamphier, C. M. Sirois, A. Verma, D. T. Golenbock, and E. Latz, “TLR9 and the recognition of self and non-self nucleic acids,” Annals of the New York Academy of Sciences, vol. 1082, pp. 31–43, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. P. M. Gaffney, G. M. Kearns, K. B. Shark et al., “A genome-wide search for susceptibility genes in human systemic Lupus erythematosus sib-pair families,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 25, pp. 14875–14879, 1998. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Shai, F. P. Quismorio, L. Li et al., “Genome-wide screen for systemic Lupus erythematosus susceptibility genes in multiplex families,” Human Molecular Genetics, vol. 8, no. 4, pp. 639–644, 1999. View at Scopus
  113. C. Kyogoku and N. Tsuchiya, “A compass that points to lupus: genetic studies on type I interferon pathway,” Genes and Immunity, vol. 8, no. 6, pp. 445–455, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Kawasaki, I. Ito, S. Ito et al., “Association of TNFAIP3 polymorphism with susceptibility to systemic Lupus erythematosus in a Japanese population,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 207578, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. Z. Cao, J. Xiong, M. Takeuchi, T. Kurama, and D. V. Goeddel, “TRAF6 is a signal transducer for interleukin-1,” Nature, vol. 383, no. 6599, pp. 443–446, 1996. View at Publisher · View at Google Scholar · View at Scopus
  116. J. K. Sandling, S. Garnier, S. Sigurdsson et al., “A candidate gene study of the type i interferon pathway implicates IKBKE and IL8 as risk loci for SLE,” European Journal of Human Genetics, vol. 19, no. 4, pp. 479–484, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. D. B. Stetson, J. S. Ko, T. Heidmann, and R. Medzhitov, “Trex1 prevents cell-intrinsic initiation of autoimmunity,” Cell, vol. 134, no. 4, pp. 587–598, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. Y. J. Crow and J. Rehwinkel, “Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity,” Human Molecular Genetics, vol. 18, no. 2, pp. R130–136, 2009. View at Scopus
  119. J. Aicardi and F. Goutieres, “Systemic Lupus erythematosus or Aicardi-Goutieres syndrome?” Neuropediatrics, vol. 31, no. 3, p. 113, 2000. View at Publisher · View at Google Scholar · View at Scopus
  120. G. Rice, W. G. Newman, J. Dean et al., “Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutières syndrome,” American Journal of Human Genetics, vol. 80, no. 4, pp. 811–815, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. M. A. Lee-Kirsch, M. Gong, D. Chowdhury et al., “Mutations in the gene encoding the 35 DNA exonuclease TREX1 are associated with systemic Lupus erythematosus,” Nature Genetics, vol. 39, no. 9, pp. 1065–1067, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. Y. J. Crow, B. E. Hayward, R. Parmar et al., “Mutations in the gene encoding the 35 DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus,” Nature Genetics, vol. 38, no. 8, pp. 917–920, 2006. View at Publisher · View at Google Scholar · View at Scopus
  123. D. A. Lehtinen, S. Harvey, M. J. Mulcahy, T. Hollis, and F. W. Perrino, “The TREX1 double-stranded DNA degradation activity is defective in dominant mutations associated with autoimmune disease,” Journal of Biological Chemistry, vol. 283, no. 46, pp. 31649–31656, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. J. M. Fye, C. D. Orebaugh, S. R. Coffin, et al., “Dominant mutation of the TREX1 exonuclease gene in lupus and Aicardi-Goutieres syndrome,” Journal of Biological Chemistry, vol. 286, no. 37, pp. 32373–32382, 2011.
  125. F. Y. K. Demirci, S. Manzi, R. Ramsey-Goldman et al., “Association of a Common Interferon Regulatory Factor 5 (IRF5) variant with increased risk of Systemic Lupus erythematosus (SLE),” Annals of Human Genetics, vol. 71, no. 3, pp. 308–311, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. D. S. C. Graham, H. Manku, S. Wagner et al., “Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation,” Human Molecular Genetics, vol. 16, no. 6, pp. 579–591, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. A. Kawasaki, C. Kyogoku, J. Ohashi et al., “Association of IRF5 polymorphisms with systemic Lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms,” Arthritis & Rheumatism, vol. 58, no. 3, pp. 826–834, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. H. O. Siu, W. Yang, C. S. Lau et al., “Association of a haplotype of IRF5 gene with systemic Lupus erythematosus in Chinese,” Journal of Rheumatology, vol. 35, no. 2, pp. 360–362, 2008. View at Scopus
  129. R. R. Graham, G. Hom, W. Ortmann, and T. W. Behrens, “Review of recent genome-wide association scans in lupus,” Journal of Internal Medicine, vol. 265, no. 6, pp. 680–688, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. S. Sigurdsson, H. H. H. Göring, G. Kristjansdottir et al., “Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic Lupus erythematosus,” Human Molecular Genetics, vol. 17, no. 6, pp. 872–881, 2008. View at Publisher · View at Google Scholar · View at Scopus
  131. C. Miceli-Richard, N. Gestermann, M. Ittah et al., “The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome,” Arthritis & Rheumatism, vol. 60, no. 7, pp. 1991–1997, 2009. View at Publisher · View at Google Scholar · View at Scopus
  132. G. Kristjansdottir, J. K. Sandling, A. Bonetti et al., “Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations,” Journal of Medical Genetics, vol. 45, no. 6, pp. 362–369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. V. Dideberg, G. Kristjansdottir, L. Milani et al., “An insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases,” Human Molecular Genetics, vol. 16, no. 24, pp. 3008–3016, 2007. View at Publisher · View at Google Scholar · View at Scopus
  134. M. Hedl and C. Abraham, “IRF5 risk polymorphisms contribute to interindividual variance in pattern recognition receptor-mediated cytokine secretion in human monocyte-derived cells,” The Journal of Immunology, vol. 188, no. 11, pp. 5348–5356, 2012.
  135. T. B. Niewold, J. A. Kelly, M. H. Flesch, L. R. Espinoza, J. B. Harley, and M. K. Crow, “Association of the IRF5 risk haplotype with high serum interferon-α activity in systemic Lupus erythematosus patients,” Arthritis & Rheumatism, vol. 58, no. 8, pp. 2481–2487, 2008. View at Publisher · View at Google Scholar · View at Scopus
  136. T. Lövgren, M. L. Eloranta, U. Båve, G. V. Alm, and L. Rönnblom, “Induction of interferon-α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG,” Arthritis & Rheumatism, vol. 50, no. 6, pp. 1861–1872, 2004. View at Publisher · View at Google Scholar · View at Scopus
  137. T. B. Niewold, J. A. Kelly, S. N. Kariuki, et al., “IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic Lupus erythematosus,” Annals of the Rheumatic Diseases, vol. 71, no. 3, pp. 463–469, 2012.
  138. K. Honda, H. Yanai, H. Negishi et al., “IRF-7 is the master regulator of type-I interferon-dependent immune responses,” Nature, vol. 434, no. 7034, pp. 772–777, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. R. Salloum, B. S. Franek, S. N. Kariuki et al., “Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-α activity in lupus patients,” Arthritis & Rheumatism, vol. 62, no. 2, pp. 553–561, 2010. View at Publisher · View at Google Scholar · View at Scopus
  140. E. G. Lee, D. L. Boone, S. Chai et al., “Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice,” Science, vol. 289, no. 5488, pp. 2350–2354, 2000. View at Publisher · View at Google Scholar · View at Scopus
  141. V. M. Dixit, S. Green, V. Sarma et al., “Tumor necrosis factor-α induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin,” Journal of Biological Chemistry, vol. 265, no. 5, pp. 2973–2978, 1990. View at Scopus
  142. A. W. Opipari, M. S. Boguski, and V. M. Dixit, “The A20 cDNA induced by tumor necrosis factor α encodes a novel type of zinc finger protein,” Journal of Biological Chemistry, vol. 265, no. 25, pp. 14705–14708, 1990. View at Scopus
  143. S. Ning and J. S. Pagano, “The A20 deubiquitinase activity negatively regulates LMP1 activation of IRF7,” Journal of Virology, vol. 84, no. 12, pp. 6130–6138, 2010. View at Publisher · View at Google Scholar · View at Scopus
  144. R. R. Graham, C. Cotsapas, L. Davies et al., “Genetic variants near TNFAIP3 on 6q23 are associated with systemic Lupus erythematosus,” Nature Genetics, vol. 40, no. 9, pp. 1059–1061, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. K. Shimane, Y. Kochi, T. Horita et al., “The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic Lupus erythematosus and rheumatoid arthritis in the japanese population,” Arthritis & Rheumatism, vol. 62, no. 2, pp. 574–579, 2010. View at Publisher · View at Google Scholar · View at Scopus
  146. I. Adrianto, F. Wen, A. Templeton et al., “Association of a functional variant downstream of TNFAIP3 with systemic Lupus erythematosus,” Nature Genetics, vol. 43, no. 3, pp. 253–258, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. C. Mauro, F. Pacifico, A. Lavorgna, et al., “ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB,” Journal of Biological Chemistry, vol. 281, no. 27, pp. 18482–18488, 2006.
  148. A. Kawasaki, S. Ito, H. Furukawa et al., “Association of TNFAIP3 interacting protein 1, TNIP1 with systemic Lupus erythematosus in a Japanese population: a case-control association study,” Arthritis research & therapy, vol. 12, no. 5, p. R174, 2010. View at Scopus
  149. L. E. Ronnblom, G. V. Alm, and K. E. Oberg, “Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors,” Annals of Internal Medicine, vol. 115, no. 3, pp. 178–183, 1991. View at Scopus
  150. L. E. Ronnblom, G. V. Alm, and K. Oberg, “Autoimmune phenomena in patients with malignant carcinoid tumors during interferon-α treatment,” Acta Oncologica, vol. 30, no. 4, pp. 537–540, 1991. View at Scopus
  151. J.J. O'Shea and R. Plenge, “JAK and STAT signaling molecules in immunoregulation and immune-mediated disease,” Immunity, vol. 36, no. 4, pp. 542–550, 2012.
  152. S. Hervas-Stubbs, J. L. Perez-Gracia, A. Rouzaut, M. F. Sanmamed, A. Le Bon, and I. Melero, “Direct effects of type I interferons on cells of the immune system,” Clinical Cancer Research, vol. 17, no. 9, pp. 2619–2627, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. B. D. Korman, D. L. Kastner, P. K. Gregersen, and E. F. Remmers, “STAT4: genetics, mechanisms, and implications for autoimmunity,” Current allergy and asthma reports, vol. 8, no. 5, pp. 398–403, 2008. View at Publisher · View at Google Scholar · View at Scopus
  154. C. O. Jacob, S. Zang, L. Li et al., “Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice,” Journal of Immunology, vol. 171, no. 3, pp. 1564–1571, 2003. View at Scopus
  155. S. Sigurdsson, G. Nordmark, S. Garnier et al., “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,” Human Molecular Genetics, vol. 17, no. 18, pp. 2868–2876, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. K. Honda, H. Yanai, A. Takaoka, and T. Taniguchi, “Regulation of the type I IFN induction: a current view,” International Immunology, vol. 17, no. 11, pp. 1367–1378, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. Y. H. Lee, S. J. Choi, J. D. Ji, and G. G. Song, “Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis,” Inflammation Research, vol. 61, no. 9, pp. 949–954, 2012.
  158. M. F. Richter, G. Duménil, G. Uzé, M. Fellous, and S. Pellegrini, “Specific contribution of Tyk2 JH regions to the binding and the expression of the interferon α/β receptor component IFNAR1,” Journal of Biological Chemistry, vol. 273, no. 38, pp. 24723–24729, 1998. View at Publisher · View at Google Scholar · View at Scopus
  159. J. Ragimbeau, E. Dondi, A. Alcover, P. Eid, G. Uzé, and S. Pellegrini, “The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression,” EMBO Journal, vol. 22, no. 3, pp. 537–547, 2003. View at Publisher · View at Google Scholar · View at Scopus
  160. B. K. Teh, J. G. Yeo, L. M. Chern, and J. Lu, “C1q regulation of dendritic cell development from monocytes with distinct cytokine production and T cell stimulation,” Molecular Immunology, vol. 48, no. 9-10, pp. 1128–1138, 2011. View at Publisher · View at Google Scholar · View at Scopus
  161. S. N. Kariuki, B. S. Franek, A. A. Kumar et al., “Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic Lupus erythematosus,” Arthritis Research and Therapy, vol. 12, no. 4, article R151, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. Y. Koldobskaya, K. Ko, A. A. Kumar, et al., “Gene-expression-guided selection of candidate Loci and molecular phenotype analyses enhance genetic discovery in systemic lupus erythematosus,” Clinical and Developmental Immunology, vol. 2012, Article ID 682018, 9 pages, 2012. View at Publisher · View at Google Scholar