MCRC Project 2, Some of Our Advances...
Advances at Northwestern University from the bone component of the MCRC study, SOLVABLE
• Established increased risk of fractures in SLE even in setting of normal BMD (Lee C et al, J Rheumatol, 2007)
• Demonstrated young African-American women with SLE have same risk of bone loss as Caucasian women with SLE (Lee C et al, Arthritis Rheum (Arthritis Care Res), 2007)
• Documented higher homocysteine levels, lower spine BMD, & more fractures in SLE compared with controls providing additional evidence that there may be common risk factors or pathophysiology for bone and CV outcomes (Rhew E et al, J Rheumatol, 2008)
• Showed significant bone geometry differences between SLE subjects and control at all hip sub-regions and that these bone geometry profiles among SLE subjects were suggestive of increased fracture risk (Alele, J Bone Min Res, epub, 2011)
Advances at Northwestern University from the cardiovascular component of the MCRC study, SOLVABLE
• Demonstrated African-American & Caucasian women with SLE have same frequency of subclinical CVD markers (Rhew E et al, Translational Res 153:51-59, 2009)
• First to show that low vitamin D is associated with CVD risk factors in SLE (Wu P et al. Arthritis Care Res 61: 1387-1395, 2009)
• Examined telomere length in patients with Systemic Lupus Erythematosus and its associations with Carotid Plaque (Skamra C et al. A pilot study: telomere length as a biomarker for cardiovascular disease in women with SLE. Poster presentation at 9th International Congress on SLE, Vancouver, BC Canada, June 25, 2010. Lupus 19 (supp): 47, 2010) (manuscript under review)
• In microarray studies, there were gene signatures which were more pronounced amongst patients relative to controls in monocytes (see Figure 2). The most striking expression difference was genes which are interferon-inducible which was present in 9/20 cases and 2/16 controls and there was another small subset of lupus patients (3/20 patients) who did not have the interferon-inducible signature but instead had up-regulation of gene expression levels in a group of genes which encode largely for chemokines and other soluble pro-inflammatory molecules (including TNF and IL-1), while the remaining 5 patients did not have any gene signature that differentiated them from controls (data not shown). A similar analyses employing in-vitro differentiated macrophages, did not demonstrate the signatures observed in monocytes. (Korman B et al. Gene Expression Profiles in Monocytes and Macrophages from Systemic Lupus Erythematosus Patients and Healthy Controls with and without An Atherosclerosis Phenotype. Arthritis Rheum, 63 (Suppl): S565, 2011.
Figure 2. Gene signature patterns in monocytes from patients with SLE relative to controls. The patients with SLE and the controls (Con) are indicated at the top of the figure. The gene symbols are indicated on the right of the figure. Red indicates that the genes were more strongly expressed, while green indicates less expression.
• Soluble E-selectin may predict progression of subclinical atherosclerosis, as measured by coronary artery calcium score and aorta calcium score, in women with systemic lupus erythematosus. Lertratanakul A et al. Arthritis Research & Therapy 2012, 14(Suppl 3):A21
Table 1. Adhesion Molecules Regressed Against Progression in Aorta Calcium Score.
(*Basis for calculation of OR is 1 SD difference)
Publications for Project #2 (2011-2012)
Alele JD, Kamen DL, Hunt KJ, Gilkeson GS, Ramsey-Goldman R. Bone Geometry Profiles in Women with and without Systemic Lupus Erythematosus (SLE). J Bone Min Res 26:2719-26,2011. PMID: 21755534.
Eimer MJ, Brickman WJ, Seshadri R, Smulevitz B, Morgan GA, *Rhew E, Cowen S, Ramsey-Goldman R, Gulati M, McPherson DD, Stone NJ, Pachman LM. Clinical Status and Cardiovascular Risk Profile of Adults with History of Juvenile Dermatomyositis– A Pilot Study. J Pediatr 159:795-801, 2011 PMID: 21784434.
Publications with MCRC Core for other lupus projects (2011-2012)
Zhao J, Wu H, Khosravi M, Cui H, Qian X, Kelly JA, Kaufman KM, Langefeld CD, Williams AH, Comeau ME, Ziegler JT, Marion MC, Adler A, Glenn SB, Alarcón-Riquelme ME on behalf of the BIOLUPUS and GENLES networks, Harley JB, Bae S-C, Lee JH, Lee J-S, Jacob CO, Vyse TV, Niewold TB, Gaffney PM, Moser KL, Kimberly RP, Edberg JC, Brown EE, Petri MA, Ramsey-Goldman R, Vila LM, Reveille JD, James JA, Gilkeson GS, Kamen DL, Freedman BI, Anaya J-M, Merrill JT, Criswell LA, Scofield RH, Stevens AM, Boackle SA, Guthridge JM, Chang D-M, Song YW, Grossman JM, Hahn BH, Goodship THJ, Cantor RM, Yung Yu C-Y, Shen N, Tsao BP. ¬Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility. PLoS Genet 2011 May;7(5):e1002079. PMID: 21637784.
Sanchez E, Comeau ME, Freedman BI, Kelly JA, Kaufman KM, Langefeld CD, Brown EE, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri M, Reveille JD, Vilá LM, Merrill JT, Tsao BP, Kamen DL, Gilkeson GS, James JA, Vyse T on behalf of SLEGEN, Gaffney PM, Jacob CO, Niewold TB, Richardson BC, Harley JB, Alarcón-Riquelme ME, Sawalha AH. Identification of novel genetic lupus susceptibility loci in African-American lupus patients using a candidate gene approach. Arthritis Rheum 63: 3493-501, 2011. PMID: 21792837.
Hughes T, Adler A, Kelly JA, Kaufman KM, Williams A, Langefeld CD, Brown EE, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri M, Reveille JD, Sanchez E, Martin J, Vilá LM, Gilkeson GS, Gaffney PM, Moser KL, Merrill JT, James JA, Vyse TJ, Alarcón-Riquelme ME on behalf of the BIOLUPUS network, Harley JB, Richardson BC, Sawalha AH. Evidence for epistatic gene-gene and sex-gene interactions in systemic lupus erythematosus. Arthritis Rheum 64:485-92, 2012. PMID: 21952918.
Sanchez E, Nadig A, Richardson BC, Freedman BI, Kaufman KM, Kelly JA, Niewold TB, Kamen DL, Gilkeson GS, Ziegler JT, Langefeld CD, Alarcón GS, Edberg JC, Ramsey-Goldman R, Petri M, Brown EE, Kimberly RP, Reveille JD, Vilá LM, Merrill JT, Anaya JM, James JA, Pons-Estel BA, Martin J, Park SY, Bang SY, Bae SC, Moser KL, Vyse TJ, Criswell LA, Gaffney PM, Tsao BP, Jacob CO, Harley JB, Alarcón-Riquelme ME; on behalf of BIOLUPUS and GENLES, Sawalha AH. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis 70: 1752-7, 2011 PMID: 21719445.
Niewold TB, Kelly JA, Kariuki SN, Franek BS1, Kumar AA, Kaufman KM, Thomas K, Walker D, Kamp S, Frost JM, Wong AK, Merrill JT, Alarcón-Riquelme ME, Tikly M, Ramsey-Goldman R, Reveille JD, Petri MA, Edberg JC, Kimberly RP, Alarcón GS, Kamen DL, Gilkeson GS, Vyse TJ, James JA, Gaffney PM, Moser KL, Crow MK, Harley JB. IRF5 Haplotypes Demonstrate Diverse Serologic Associations which Predict Serum Interferon Alpha Activity and Explain the Majority of the Genetic Association with Systemic Lupus Erythematosus. Ann Rheum Dis 71:463-8, 2012. PMID: 22088620.
Santiago-Casas Y, Vilá LM, McGwin Jr G, Petri M, Ramsey-Goldman R, Reveille JD, Kimberly RP, Alarcón GS, Elizabeth E. Brown EE. Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort. Arthritis Care Res 64:704-12, 2012. PMID: 22190480.
Hughes T, Adler A, Merrill JT, Kelly JA, Kaufman KM, Williams A, Langefeld CD, Gilkeson GS, Martin J, Alarcón GS, Brown EE, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri M, Reveille JD, Vilá, LM, Gaffney PM, Moser KL, Vyse TJ, Alarcón-Riquelme MD on behalf of the BIOLUPUS network , James JA, Scofield RH, Harley JB, Richardson BC, Sawalha AH. Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus. Ann Rheum Dis. 71:694-9, 2012. PMID: 22110124.
Namjou B, Choi C-B, Harley OTW, Kim K, Kelly JA, Glenn SB, Ojwang JO, Adler A, Alarcón-Riquelme ME, Gallant CJ, Boackle SA, Criswell LA, Kimberly RP, Brown E, Edberg J, Stevens AM, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya J-M, Kim E-M, Guthridge J, Merrill JT, Petri M, Ramsey Goldman R, Vila L, Niewold TB, Martin J, Bernardo A. Pons-Estel BA, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams A, Comeau M, Reveille JD, Kang C, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Bae S-C. Evaluation of TRAF6 in a large multi-ancestral lupus cohort. Arthritis Rheum 64:1960-9, 2012 PMID: 22231568.
Lin CP, Adrianto I, Lessard CJ, Kelly JA, Kaufman KM, Guthridge JM, Freedman BI, Anaya J-M, Alarcón-Riquelme ME on behalf of the BIOLUPUS and GENLES Networks, Martin J, Glenn S, Adler A, Bae S-C, Park S-Y, Boackle SA, Brown EE, Edberg JC, Alarcón GS, Petri MA, Criswell LA, Ramsey-Goldman R, Reveille JD, Vila LM, Gilkeson GS, Kamen DL, Ziegler J, Jacob JO, Rasmussen A, James JA3, Kimberly RP, Merrill JT, Niewold TB, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Moser KL, Harley JB, Gaffney PM, Montgomery CG. Role of MYH9 and APOL1 in African and non-African populations with Lupus Nephritis. Genes Immun 13:232-8, 2012. PMID: 22189356.
Lessard CJ, Adrianto I, Ice JA, Wiley GB, Kelly JA, Glenn SB, Adler AJ, Li H, Rasmussen A, Williams AH, Ramos PS, Grundahl KM, Gallant CJ, Alarcón-Riquelm ME for the BIOLUPUS and GENLES Networks1,5, Alarcon GS, Anaya J-M, Bae S-C, Boackle SA, h E Brown EB, ChangD-M, Criswell LA, Edberg JC, Freedman BI, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Park S-Y, Petri MA, Pons-Estel BA, Ramsey-Goldman R, Reveille JD, Scofield RH, Song YW, Stevens AM, Tsao BP, Vila LM, Vyse TJ, Yu C-Y, Guthridge JM, Kaufman KM, Harley JB, Wakeland EK, Langefeld CD, Gaffney PM, Montgomery CG, Moser KL. Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale, multi-racial replication study. Am J Hum Genet 90:648-60, 2012. PMID:22464253
Kim K, Brown EE, Choi C-B, Alarcón-Riquelme MEon behalf of BIOLUPUS, Kelly JA, Glenn SB, Ojwang JO,, Adler A, Bang S-Y, Lee H-S, Boackle SA, Criswell LA, Kim T, Alarcon GS, Edberg JC, Stevens MA, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya J-M, Guthridge JM, Nath SK, Richardson B, Sawalha AH, Kang YM, Shim SC, Suh C-H, Lee S-K, Kim C-S, Merrill JT, Petri M, Ramsey-Goldman R, Vilá LM, Niewold TB, Martin J, Pons-Estel BA on behalf of GENLES, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams A, Comeau M, Reveille JD, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Kang C, Kimberly RP,Bae S-C. Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestry populations. Ann Rheum Dis 2012 Apr 20. [Epub ahead of print] PMID: 22523428.
Kaiser R, Li Y, Chang M, Catanese J, Begovich AB, Brown EE, Edberg JC, McGwin G, Alarcón GS, Ramsey-Goldman R, Reveille JD, Vilá LM, Petri MA, Kimberly RP, Taylor K, Criswell LA. Genetic Risk Factors for Thrombosis in Systemic Lupus Erythematosus. J Rheumatol 39(8):1603-10, 2012. PMID:22707612.
Wang S, Adrianto I, Wiley GB, Lessard CJ; Kelly JA; Adler AJ, Glenn SB, Williams AH, Ziegler JT, Comeau ME, Marion MC, Wakeland BE; Liang C, Kaufman KM, Guthridge JM, Alarcón-Riquelme ME, Alarcón GS, Anaya J-M; Bae S-C, Kim J-H, Joo Y-B, Boackle SA, Brown EE, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, Criswell LA, Edberg JC, Freedman BI, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Pons-Estel BA, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Harley JB, Wakeland EK, Moser KL, Montgomery CG, Gaffney PM. A Functional Haplotype of UBE2L3 Confers Risk for Systemic Lupus Erythematosus. Genes Immun 13:380-7, 2012. PMID: 22476155
Sánchez E, Rassmusen A, Riba L, Acevedo E, Kelly JA, Langefeld CD, García de la Torre I, Maradiaga-Ceceña MA, Cardiel-Ríos MH, Esquivel J, Rodriguez J, Moctezuma JF, Miranda P, Espada G, Perandones C, Castel C, Laborde HA, Alba P, Musuruana J, Goecke A, Foster C, Anaya J-M, Kaufman KM, Adler A, Brown EE, Alarcón G, Kimberly RP, Edberg JC, Criswell L, Gilkeson GS, Niewold TB, MD, Martin J, Vyse TJ, Ramsey-Goldman R, Petri M, Merril JT, Reveille JD, Tsao BP, Orozco L, Baca V, James JA, Harley JB, Tusié-Luna T, Pons-Estel BA, Jacob CO, Alarcon-Riquelme ME. Impact of Amerindian Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Admixed Populations. Arthritis Rheum 2012 Aug 8. doi:10.1002/art.34650. [Epub ahead of print] PMID: 22886787.
Kaufman KM, Kelly JA, Hughes T, Adler A, Sanchez E, Ojwang JO, Langefeld CD, Ziegler JT, Williams AH, Comeau ME, Marion MC, Glenn SB, James JA, Guthridge J, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri M, Reveille JD, Brown EE, Vilá LM, Anaya J-M, Boackle SA,Stevens AM, Freedman BI, Criswell LA, Jacob CO, Scofield RH, Gilkeson GS, Moser KL, Gaffney PM, Merrill JT, Niewold TB, Vyse TJ, Bae S-C, Alarcón-Riquelme ME, on behalf of the BIOLUPUS network, Harley JB, Sawalha AH, Tsao BP. Fine Mapping of Xq28: Both MECP2 and IRAK1 Contribute to Risk for Systemic Lupus Erythematosus in Multiple Ancestral Groups. Ann Rheum Dis 2012 Aug 17. [Epub ahead of print] PMID: 22904263.
Adrianto I, Wang S, Wiley GB, Lessard CJ, Kelly JA, Adler A, Glenn SB, Williams A, Ziegler J, Comeau ME, Marion M, Wakeland BE, Liang C, Kaufman KM, Guthridge JM, Alarcon-Riquelme ME on behalf of the BIOLUPUS and GENLES Networks, Alarcon GS, Anaya JM, Bae SC, Boackle SA, Brown, EE, Petri MA, Ramsey-Goldman R, Reveille JD, Vila LM, Criswell LA, Edberg JC, Freedman BI, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Pons-Estel BA, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Harley JB, Wakeland EK, Moser KL, Montgomery CG, Gaffney PM. Two Independent Risk Haplotypes in TNIP1 are Associated with Systemic Lupus Erythematosus. Arthritis Rheum 2012 Jul 25. doi: 10.1002/art.34642. [Epub ahead of print] PMID: 22833143.
Kaiser R, Taylor KE, Deng Y, Li Y, Zhao J, Li Y, Nititham J, Chang M, Catanese J, Begovich AB, Brown, EE, Edberg JC, McGwin G, Alarcon GS, Ramsey-Goldman R, Reveille JD, Vila LM, Petri M, Kimberly RP, Feng X, Sun L, Shen N, Li W, Lu J-X, Wakeland EK, Li ZQ, Yang, W, Lau YL, Liu FL, Chang DM, Yu CY, Song YW, Howe H and the Tan Tock Seng Hospital (TTSH) Systemic Lupus Erythematosus Study Group, , Tsao BP, Criswell LA. SNPs in MTHRF and VKORC1 are Risk Factors for Systemic Lupus Erythematosus in Asians Arthritis Rheum in press.
Urowitz MB, Gladman DD, Ibañez D, Bae SC, Gordon C, Clarke A, Bernatsky S, Hanly J, Fortin PR, Isenberg D, Rahman A, Sanchez-Guerrero J, Wallace D, Ginzler E, Alarcón G, Merrill J, Bruce I, Sturfelt G, Nived O, Steinsson K, Khamashta M, Petri M, Manzi S, Ramsey-Goldman R, Dooley M, Van Vollenhoven R, Ramos M, Stoll T, Zoma A, Kalunian K, Aranow C, Maddison P. Evolution of Disease Burden Over 5 Years in a Multicentre Inception SLE Cohort. Arthritis Care Res 64: 132-7, 2012 PMID: 21954226.
Hanly JG, Urowitz MB, Su L, Gordon C, Bae S-C, Sanchez-Guerrero J, Romero-Diaz J, Wallace DJ, Clarke AE, Ginzler EM, Merrill JT, Isenberg DA, Rahman A, Petri M, Fortin PR, Gladman DD, Bruce1 IN, Steinsson K, Dooley MA, Khamashta MA, Alarcón GS, Fessler BJ, Ramsey-Goldman R, Manzi S, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals m, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Theriault C, Thompson K, Farewell V. Seizure disorders in Systemic Lupus Erythematosus. Results from an international, prospective, inception cohort study. Ann Rheum Dis 71:1502–1509, 2012. PMID: 22492779.
Parker B, Urowitz MB, Gladman DD, Lunt M, Donn R, Ibañez D, Gordon C, Bae SC, Clarke A, Bernatsky S, Fessler B, Hanly JG, Isenberg D, Rahman A, Sanchez-Guerrero J, Romero-Diaz J, Fortin PR, Wallace D, Vasudevan A, Merrill J, Alarcón GS, Sturfelt G, Nived O, Steinsson K, Khamashta M, Petri M, Manzi S, Dooley MA, Ramsey-Goldman R, Aranow C, Van Vollenhoven R, Ramos-Casals M, Stoll T, Kalunian K, Zoma A, Maddison P, Bruce IN; for the Systemic Lupus International Collaborating Clinics (SLICC). Predictors of the Metabolic Syndrome in Systemic Lupus Erythematosus: Data from an International Inception Cohort. Ann Rheum Dis 2012 Sep 3. [Epub ahead of print] PMID: 22945501.
