Autoimmune Disease Genetics 2013View this Special Issue
Editorial | Open Access
Autoimmune Disease Genetics 2013
The familial predilection toward autoimmunity is in part due to genetic risk factors, and recent studies have greatly expanded our understanding of the complex genetic architecture underlying autoimmune disease. Technical advances and the assembly of large patient cohorts have resulted in rapid progress in the field, which does not appear to be slowing. Studies which have included multiple ancestral backgrounds have demonstrated differences in risk factors between ancestral backgrounds, as well as some similarities [1–3]. Also, genetic studies examining subphenotypes in autoimmune diseases have illustrated the idea of biological diversity within a complex condition, that different individuals with a given condition have different genetic risk factors, and some of the clinical differences between patients are likely related to this fact [4–6]. In these ways, understanding the genetic basis of disease provides us with some tools that could eventually be useful in developing more individualized diagnostic and therapeutic strategies, enabling personalized medicine.
In the current issue, a series of papers highlight some exciting topics within autoimmune disease genetics. M. G. Zavala-Cerna et al. explore genetic associations between PAD4 and rheumatoid arthritis in a Mexican cohort. The PAD4 enzyme is implicated in posttranslational protein modification characteristically targeted by rheumatoid arthritis-associated autoantibodies. B. N. Frederiksen et al. examine genetic polymorphisms underlying type I diabetes and islet cell autoimmunity, finding both age- and disease-stage relevant differences in association. This study illustrates the complex ways in which genetic factors can influence disease, and it is likely that this complexity occurs in many different autoimmune diseases. Genetic risk alleles may depend on other factors such as age, disease stage, and environment to influence risk of disease. Discovering these relationships will greatly improve our understanding of autoimmune disease pathogenesis. C. E. Weckerle et al. report a familial aggregation study looking at circulating levels of tumor necrosis factor alpha, a cytokine which is elevated in lupus patients , in unaffected members of lupus families. Previous work had demonstrated familial correlation in type I interferon levels , and the current study documents a familial relationship in tumor necrosis factor alpha levels. Interestingly, while type I interferon was only correlated within genetically related family members and not correlated between patients and spouses, tumor necrosis factor alpha was correlated between lupus patients and their spouses, suggesting a potential environmental influence on tumor necrosis factor alpha levels.
S. A. Zavaleta-Muñiz et al. study polymorphisms in the IL6 gene with regard to susceptibility to rheumatoid arthritis. A. Zóka et al. provide a comprehensive review of the alterations in the immune system which are related to type I diabetes. H. C. Chai et al. examine polymorphisms in genes within the Toll-like receptor and type I interferon pathways in systemic lupus erythematosus patients from a South Asian population, extending our knowledge of these susceptibility genes to an additional world population. While one issue cannot be comprehensive, the studies included in this issue provide an overview of some of the current frontiers in the genetics of autoimmune disease.
Timothy B. Niewold
George N. Goulielmos
- E. Sánchez, M. E. Comeau, B. I. Freedman et al., “Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study,” Arthritis and Rheumatism, vol. 63, no. 11, pp. 3493–3501, 2011.
- S. Agik, B. S. Franek, A. A. Kumar et al., “The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus: a recessive effect upon subphenotypes,” Journal of Rheumatology, vol. 39, no. 1, pp. 73–78, 2012.
- L. B. Hughes, R. J. Reynolds, E. E. Brown et al., “Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans,” Arthritis and Rheumatism, vol. 62, no. 12, pp. 3547–3553, 2010.
- 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. 463–468, 2012.
- K. Ko, Y. Koldobskaya, E. Rosenzweig, and T. B. Niewold, “Activation of the Interferon pathway is dependent upon autoantibodies in African-American SLE patients, but not in European-American SLE patients,” Frontiers in Immunology, vol. 4, article 309, 2013.
- L. Bossini-Castillo, C. de Kovel, H. Kallberg, R. van 't Slot, A. Italiaander, and M. Coenen, “A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides,” Annals of the Rheumatic Diseases, 2014.
- C. E. Weckerle, D. Mangale, B. S. Franek et al., “Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus,” Arthritis and Rheumatism, vol. 64, no. 9, pp. 2947–2952, 2012.
- T. B. Niewold, J. Hua, T. J. A. Lehman, J. B. Harley, and M. K. Crow, “High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus,” Genes & Immunity, vol. 8, no. 6, pp. 492–502, 2007.
Copyright © 2014 Timothy B. Niewold 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.