Both environmental as well as genetic factors have been documented to contribute to autoimmunity, as is evident from the accompanying articles in this journal. This raises an important question–which of these two elements plays a more important role in the genesis of autoimmunity? This report encapsulates a geneticist's perspective on this interesting question. Though lupus is used as an example in this essay, the proposed model is envisaged to operate in other autoimmune diseases as well.
Raman K , Mohan C . Genetic underpinnings of autoimmunity–lessons from studies in arthritis, diabetes, lupus and multiple sclerosis . Curr Opin Immunol2003; 15: 651–659 .
2.
Kono DH , Theofilopoulos AN . Genetics of systemic autoimmunity in mouse models of lupus . Int Rev Immunol2000; 19: 367–387 .
3.
Morel L , Rudofsky UH , Longmate JA , Schiffenbauer J , Wakeland EK . Polygenic control of susceptibility to murine systemic lupus erythematosus . Immunity1994; 1: 219-219 .
4.
Xie S , Mohan C . Divide and conquer–the power of congenic strains. Clin Immunol2003; YCLIM-05443.
5.
Henry T , Mohan C . Lesson in lupus from congenic strains . Archivum Immunologiae et Therapiae Experimentalis2005; 53: 207–212 .
6.
Mohan C , Alas E , Morel L , Yang P , Wakeland EK . Genetic dissection of SLE pathogenesis: Sle1 on murine chromosome 1 leads to selective loss of tolerance to chromatin components . J Clin Invest1998; 101: 1362–1372 .
7.
Mohan C , Morel L , Yang P , Deng A , Wakeland EK . Genetic dissection of SLE pathogenesis: Sle2 on murine chromosome 4 leads to B-cell hyperactivity . J Immunol1997; 159: 454–465 .
8.
Mohan C , Yu Y , Morel L , Yang P , Wakeland EK . Genetic dissection of SLE pathogenesis: Sle3 impacts T-cell activation, differentiation and cell death . J Immunol1999; 162: 6492–6502 .
9.
Mohan C , Morel L , Yang P et al. Genetic dissection of SLE pathogenesis: A recipe for nephrophilic autoantibodies . J Clin Invest1999; 103: 1685–1695 .
10.
Morel L , Croker BP , Blenman KR et al. Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains . Proc Natl Acad Sci USA2000; 97: 6670–6675 .
11.
Kumar KR , Li L , Yan M et al. Regulation of B-cell tolerance by the lupus susceptibility gene Ly108 . Science2006; 312: 1665–1669
12.
Zhu J , Liu X , Xie C et al. Genetic dissection of lupus: T-cell hyperactivity as a consequence of hyperstimulatory antigen presenting cells . J Clin Invest2005; 115: 1869–1878 .
