BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities. OBJECTIVES: To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE. METHODS: The relationship between the age at disease onset and SLE manifestations were explored in a multi-racial cohort of 1317 patients. Patients with SLE were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset. RESULTS: Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values <0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in adult-onset SLE (p=0.0027). With age of onset ≥50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody and seizures were reduced. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specific manner: by an average of 48% in Gullah and 25% in African-Americans, but this was not significant in Hispanic and European-American lupus patients. CONCLUSIONS: The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.
BACKGROUND:Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities. OBJECTIVES: To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE. METHODS: The relationship between the age at disease onset and SLE manifestations were explored in a multi-racial cohort of 1317 patients. Patients with SLE were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset. RESULTS: Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values <0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in adult-onset SLE (p=0.0027). With age of onset ≥50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody and seizures were reduced. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specific manner: by an average of 48% in Gullah and 25% in African-Americans, but this was not significant in Hispanic and European-American lupuspatients. CONCLUSIONS: The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.
Authors: P S Ramos; J A Kelly; C Gray-McGuire; G R Bruner; A N Leiran; C M Meyer; B Namjou; K J Espe; W A Ortmann; M Reichlin; C D Langefeld; J A James; P M Gaffney; T W Behrens; J B Harley; K L Moser Journal: Genes Immun Date: 2006-06-15 Impact factor: 2.676
Authors: J Wang; S Yang; J J Chen; S M Zhou; S M He; Y H Liang; W Meng; X F Yan; J J Liu; D Q Ye; X J Zhang Journal: Arch Dermatol Res Date: 2007-03 Impact factor: 3.017
Authors: R Hal Scofield; Gail R Bruner; Bahram Namjou; Robert P Kimberly; Rosalind Ramsey-Goldman; Michelle Petri; John D Reveille; Graciela S Alarcón; Luis M Vilá; Jeff Reid; Bryan Harris; Shibo Li; Jennifer A Kelly; John B Harley Journal: Arthritis Rheum Date: 2008-08
Authors: John B Harley; Marta E Alarcón-Riquelme; Lindsey A Criswell; Chaim O Jacob; Robert P Kimberly; Kathy L Moser; Betty P Tsao; Timothy J Vyse; Carl D Langefeld; Swapan K Nath; Joel M Guthridge; Beth L Cobb; Daniel B Mirel; Miranda C Marion; Adrienne H Williams; Jasmin Divers; Wei Wang; Summer G Frank; Bahram Namjou; Stacey B Gabriel; Annette T Lee; Peter K Gregersen; Timothy W Behrens; Kimberly E Taylor; Michelle Fernando; Raphael Zidovetzki; Patrick M Gaffney; Jeffrey C Edberg; John D Rioux; Joshua O Ojwang; Judith A James; Joan T Merrill; Gary S Gilkeson; Michael F Seldin; Hong Yin; Emily C Baechler; Quan-Zhen Li; Edward K Wakeland; Gail R Bruner; Kenneth M Kaufman; Jennifer A Kelly Journal: Nat Genet Date: 2008-01-20 Impact factor: 38.330
Authors: L B Tucker; A G Uribe; M Fernández; L M Vilá; G McGwin; M Apte; B J Fessler; H M Bastian; J D Reveille; G S Alarcón Journal: Lupus Date: 2008-04 Impact factor: 2.911
Authors: I E A Hoffman; B R Lauwerys; F De Keyser; T W J Huizinga; D Isenberg; L Cebecauer; J Dehoorne; R Joos; G Hendrickx; F Houssiau; D Elewaut Journal: Ann Rheum Dis Date: 2008-10-17 Impact factor: 19.103
Authors: Aimee O Hersh; Emily von Scheven; Jinoos Yazdany; Pantelis Panopalis; Laura Trupin; Laura Julian; Patricia Katz; Lindsey A Criswell; Edward Yelin Journal: Arthritis Rheum Date: 2009-01-15
Authors: Robert R Graham; Chieko Kyogoku; Snaevar Sigurdsson; Irina A Vlasova; Leela R L Davies; Emily C Baechler; Robert M Plenge; Thearith Koeuth; Ward A Ortmann; Geoffrey Hom; Jason W Bauer; Clarence Gillett; Noel Burtt; Deborah S Cunninghame Graham; Robert Onofrio; Michelle Petri; Iva Gunnarsson; Elisabet Svenungsson; Lars Rönnblom; Gunnel Nordmark; Peter K Gregersen; Kathy Moser; Patrick M Gaffney; Lindsey A Criswell; Timothy J Vyse; Ann-Christine Syvänen; Paul R Bohjanen; Mark J Daly; Timothy W Behrens; David Altshuler Journal: Proc Natl Acad Sci U S A Date: 2007-04-05 Impact factor: 11.205
Authors: Amr H Sawalha; Lu Wang; Ajay Nadig; Emily C Somers; W Joseph McCune; Travis Hughes; Joan T Merrill; R Hal Scofield; Faith M Strickland; Bruce Richardson Journal: J Autoimmun Date: 2012-02-03 Impact factor: 7.094
Authors: Emily C Somers; Wendy Marder; Patricia Cagnoli; Emily E Lewis; Peter DeGuire; Caroline Gordon; Charles G Helmick; Lu Wang; Jeffrey J Wing; J Patricia Dhar; James Leisen; Diane Shaltis; W Joseph McCune Journal: Arthritis Rheumatol Date: 2014-02 Impact factor: 10.995
Authors: Sarah E Bergen; Colm T O'Dushlaine; Phil H Lee; Ayman H Fanous; Douglas M Ruderfer; Stephan Ripke; Patrick F Sullivan; Jordan W Smoller; Shaun M Purcell; Aiden Corvin Journal: Schizophr Res Date: 2014-02-26 Impact factor: 4.939