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3. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus

Author

Zhao, Jian, Wu, Hui, Langefeld, Carl D., Kaufman, Kenneth M., Kelly, Jennifer A., Bae, Sang-Cheol, Alarcón, Graciela S., Anaya, Juan-Manuel, Criswell, Lindsey A., Freedman, Barry I., Kamen, Diane L., Gilkeson, Gary S., Jacob, Chaim O., James, Judith A., Merrill, Joan T., Gaffney, Patrick M., Sivils, Kathy Moser, Niewold, Timothy B., Petri, Michelle A., Song, Seung Taek, Jeong, Hye-jin, Ramsey-Goldman, Rosalind, Reveille, John D., Hal Scofield, R., Stevens, Anne M., Boackle, Susan A., Vilá, Luis M., Chang, Deh-Ming, Song, Yeong Wook, Vyse, Timothy J., Harley, John B., Brown, Elizabeth E., Edberg, Jeffrey C., Kimberly, Robert P., Hahn, Bevra H., Grossman, Jennifer M., Tsao, Betty P., and La Cava, Antonio

Published
2015
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4. 1401 A Genome Wide Association Scan of SLE genetic risk in a cohort of African-American persons

Author

Harley, Isaac TW, primary, Sun, Celi, additional, Williams, Adrienne H, additional, Ziegler, Julie T, additional, Comeau, Mary E, additional, Marion, Miranda C, additional, Glenn, Stuart B, additional, Adler, Adam, additional, Frank-Pearce, Summer G, additional, Shen, Nan, additional, Kelly, Jennifer A, additional, Namjou-Khales, Bahram, additional, Petri, Michelle, additional, Alarcon-Riquelme, Marta, additional, Joseph McCune, W, additional, Gaffney, Patrick, additional, Sivils, Kathy, additional, Salmon, Jane E, additional, Weisman, Michael H, additional, Edberg, Jeffrey C, additional, Brown, Elizabeth E, additional, Utset, Tammy, additional, Criswell, Lindsey A, additional, Jacob, Chaim O, additional, Tsao, Betty, additional, Vyse, Timothy J, additional, James, Judith A, additional, Gilkeson, Gary S, additional, Kamen, Diane L, additional, Montgomery, Courtney, additional, Merrill, Joan T, additional, Nath, Swapan K, additional, Laurynenka, Viktoryia, additional, Chepelev, Iouri, additional, Harris-Lewis, Valerie, additional, Hal Scofield, R, additional, Kimberly, Robert P, additional, Langefeld, Carl D, additional, Harley, John B, additional, and Kaufman, Kenneth M, additional

Published
2022
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5. 902 Loss-of-function variants inSAT1cause X-linked Childhood-onset Systemic Lupus Erythematosus

Author

Xu, Lingxiao, primary, Zhao, Jian, additional, Sun, Qing, additional, Xu, Xue, additional, Wang, Lei, additional, Liu, Ting, additional, Wu, Yunjuan, additional, Zhu, Jingfeng, additional, Geng, Linyu, additional, Deng, Yun, additional, Awgulewitsch, Alexander, additional, Kamen, Diane L, additional, Oates, Jim C, additional, Raj, Prithvi, additional, Wakeland, Edward K, additional, Hal Scofield, R, additional, Guthridge, Joel M, additional, James, Judith A, additional, Hahn, Bevra H, additional, McCurdy, Deborah K, additional, Wang, Fang, additional, Zhang, Miaojia, additional, Tan, Wenfeng, additional, Gilkeson, Gary S, additional, and Tsao, Betty P, additional

Published
2022
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6. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Author

Kottyan, Leah C., Zoller, Erin E., Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A., Rupert, Andrew M., Lessard, Christopher J., Vaughn, Samuel E., Marion, Miranda, Weirauch, Matthew T., Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G., Hirschfield, Gideon M., Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A., Nath, Swapan K., Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G., Gøransson, Lasse G., Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S., Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T., Lessard, James A., Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G., Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L., Segal, Barbara M., Merrill, Joan T., James, Judith A., Guthridge, Joel M., Hal Scofield, R., Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A., Criswell, Lindsey A., Gilkeson, Gary, Kamen, Diane L., Jacob, Chaim O., Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S., Reveille, John D., Vilá, Luis M., Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I., Niewold, Timothy, Stevens, Anne M., Tsao, Betty P., Ying, Jun, Mayes, Maureen D., Gorlova, Olga Y., Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Moser Sivils, Kathy L., Gaffney, Patrick M., Langefeld, Carl D., Harley, John B., and Kaufman, Kenneth M.

Published
2015
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16. Identification of a Sjögrens syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons

Author

Li, He, Ragna Reksten, Tove, Ice, John A., Kelly, Jennifer A., Adrianto, Indra, Rasmussen, Astrid, Wang, Shaofeng, He, Bo, Grundahl, Kiely M., Glenn, Stuart B., Miceli-Richard, Corinne, Bowman, Simon, Lester, Sue, Eriksson, Per, Eloranta, Maija-Leena, Brun, Johan G., Goransson, Lasse G., Harboe, Erna, Guthridge, Joel M., Kaufman, Kenneth M., Kvarnstrom, Marika, Cunninghame Graham, Deborah S., Patel, Ketan, Adler, Adam J., Darise Farris, A., Brennan, Michael T., Chodosh, James, Gopalakrishnan, Rajaram, Weisman, Michael H., Venuturupalli, Swamy, Wallace, Daniel J., Hefner, Kimberly S., Houston, Glen D., Huang, Andrew J. W., Hughes, Pamela J., Lewis, David M., Radfar, Lida, Vista, Evan S., Edgar, Contessa E., Rohrer, Michael D., Stone, Donald U., Vyse, Timothy J., Harley, John B., Gaffney, Patrick M., James, Judith A., Turner, Sean, Alevizos, Ilias, Anaya, Juan-Manuel, Rhodus, Nelson L., Segal, Barbara M., Montgomery, Courtney G., Hal Scofield, R., Kovats, Susan, Mariette, Xavier, Ronnblom, Lars, Witte, Torsten, Rischmueller, Maureen, Wahren-Herlenius, Marie, Omdal, Roald, Jonsson, Roland, Ng, Wan-Fai, Nordmark, Gunnel, Lessard, Christopher J., Sivils, Kathy L., Li, He, Ragna Reksten, Tove, Ice, John A., Kelly, Jennifer A., Adrianto, Indra, Rasmussen, Astrid, Wang, Shaofeng, He, Bo, Grundahl, Kiely M., Glenn, Stuart B., Miceli-Richard, Corinne, Bowman, Simon, Lester, Sue, Eriksson, Per, Eloranta, Maija-Leena, Brun, Johan G., Goransson, Lasse G., Harboe, Erna, Guthridge, Joel M., Kaufman, Kenneth M., Kvarnstrom, Marika, Cunninghame Graham, Deborah S., Patel, Ketan, Adler, Adam J., Darise Farris, A., Brennan, Michael T., Chodosh, James, Gopalakrishnan, Rajaram, Weisman, Michael H., Venuturupalli, Swamy, Wallace, Daniel J., Hefner, Kimberly S., Houston, Glen D., Huang, Andrew J. W., Hughes, Pamela J., Lewis, David M., Radfar, Lida, Vista, Evan S., Edgar, Contessa E., Rohrer, Michael D., Stone, Donald U., Vyse, Timothy J., Harley, John B., Gaffney, Patrick M., James, Judith A., Turner, Sean, Alevizos, Ilias, Anaya, Juan-Manuel, Rhodus, Nelson L., Segal, Barbara M., Montgomery, Courtney G., Hal Scofield, R., Kovats, Susan, Mariette, Xavier, Ronnblom, Lars, Witte, Torsten, Rischmueller, Maureen, Wahren-Herlenius, Marie, Omdal, Roald, Jonsson, Roland, Ng, Wan-Fai, Nordmark, Gunnel, Lessard, Christopher J., and Sivils, Kathy L.

Abstract

Sjogrens syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2-5-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3 end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease., Funding Agencies|NIH [P50AR0608040, 1R01AR065953, 5R01DE015223, 5RC2AR058959, 5P01AR049084, 5P30AR053483, 5U19AI082714, U19AI056363, 1R01DE018209, 5R01DE018209, 8P20GM103456, 1P30GM110766, 1R03AR065786, 5R37AI024717, 5P01AI083194, 7S10RR027190-02, 1U01AI101934, U54GM104938, S10RR026735, 5P30GM103510]; National Institute of Dental and Craniofacial Research; US Department of Veterans Affairs IM MA 9; USA Department of Defense [PR094002]; American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award; Oklahoma Medical Research Foundation; Sjogrens Syndrome Foundation; Phileona Foundation; French ministry of health: PHRC [2006-AOM06133]; French ministry of research [ANR-2010-BLAN-1133]

Published
2017
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17. Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjogrens Syndrome

Author

Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Erick Kaufman, C., Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Magnusson Bucher, Sara, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Alarcon-Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan-Fai, Rasmussen, Astrid, Sivils, Kathy L., Hal Scofield, R., Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Erick Kaufman, C., Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Magnusson Bucher, Sara, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Alarcon-Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan-Fai, Rasmussen, Astrid, Sivils, Kathy L., and Hal Scofield, R.

Abstract

Objective. Sjogrens syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of similar to 10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods. We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results. Among similar to 2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among similar to 2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in similar to 1 in 25,000-50,000 live female births, while partial triplications are even rarer. Conclusion. Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative., Funding Agencies|NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [AR-053483, AR-053734]; NIH (National Institute of Allergy and Infectious Diseases) [AI-082714]; NIH (National Institute of General Medical Sciences) [GM-104938]; US Department of Veterans Affairs; Lupus Research Institute; UCB; Ionis; Ampel; Bristol-Myers Squibb; Pfizer; Regeneron; Sanofi/Genzyme; GlaxoSmithKline; Novartis; Abbott; Boston Pharmaceuticals

Published
2017
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18. X Chromosome Dose and Sex Bias in Autoimmune Diseases

Author

Liu, Ke, Kurien, Biji T., Zimmerman, Sarah L., Kaufman, Kenneth M., Taft, Diana H., Kottyan, Leah C., Lazaro, Sara, Weaver, Carrie A., Ice, John A., Adler, Adam J., Chodosh, James, Radfar, Lida, Rasmussen, Astrid, Stone, Donald U., Lewis, David M., Li, Shibo, Koelsch, Kristi A., Igoe, Ann, Talsania, Mitali, Kumar, Jay, Maier-Moore, Jacen S., Harris, Valerie M., Gopalakrishnan, Rajaram, Jonsson, Roland, Lessard, James A., Lu, Xianglan, Eric Gottenberg, Jacques, Manuel Anaya, Juan, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Mei, Gabor G., Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Eriksson, Per, Omda, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Sega, Barbara M., Vvse, Timothy J., Wahren-Herlenius, Marie, Witte, Torsten, Pons-Este, Bernardo, Alarcon-Riquelme, Marta E., Guthridge, Joel M., James, Judith A., Lessard, Christopher J., Kelly, Jennifer A., Thompson, Susan D., Gaffney, Patrick M., Montgomery, Courtney G., Edberg, Jeffrey C., Kimberly, Robert P., Alarcon, Gracicla S., Langefeld, Carl L., Gilkeson, Gary S., Kamen, Diane L., Tsao, Betty P., Joseph McCune, W., Salmon, Jane E., Merrill, Joan T., Weisman, Michael H., Wallace, Daniel J., Utset, Tammy, Bottinger, Erwin P., Amos, Christopher I., Siminovitch, Katherine A., Mariette, Xavier, Sivils, Kathy L., Harley, John B., Hal Scofield, R., Liu, Ke, Kurien, Biji T., Zimmerman, Sarah L., Kaufman, Kenneth M., Taft, Diana H., Kottyan, Leah C., Lazaro, Sara, Weaver, Carrie A., Ice, John A., Adler, Adam J., Chodosh, James, Radfar, Lida, Rasmussen, Astrid, Stone, Donald U., Lewis, David M., Li, Shibo, Koelsch, Kristi A., Igoe, Ann, Talsania, Mitali, Kumar, Jay, Maier-Moore, Jacen S., Harris, Valerie M., Gopalakrishnan, Rajaram, Jonsson, Roland, Lessard, James A., Lu, Xianglan, Eric Gottenberg, Jacques, Manuel Anaya, Juan, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Mei, Gabor G., Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Eriksson, Per, Omda, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Sega, Barbara M., Vvse, Timothy J., Wahren-Herlenius, Marie, Witte, Torsten, Pons-Este, Bernardo, Alarcon-Riquelme, Marta E., Guthridge, Joel M., James, Judith A., Lessard, Christopher J., Kelly, Jennifer A., Thompson, Susan D., Gaffney, Patrick M., Montgomery, Courtney G., Edberg, Jeffrey C., Kimberly, Robert P., Alarcon, Gracicla S., Langefeld, Carl L., Gilkeson, Gary S., Kamen, Diane L., Tsao, Betty P., Joseph McCune, W., Salmon, Jane E., Merrill, Joan T., Weisman, Michael H., Wallace, Daniel J., Utset, Tammy, Bottinger, Erwin P., Amos, Christopher I., Siminovitch, Katherine A., Mariette, Xavier, Sivils, Kathy L., Harley, John B., and Hal Scofield, R.

Abstract

Objective. More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47, XXX; occurring in similar to 1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogrens syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. Methods. All subjects in this study were female. We identified subjects with 47, XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47, XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. Results. We found 47, XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47, XXX. There was an excess of 47, XXX among SLE and SS patients. Conclusion. The estimated prevalence of SLE and SS in women with 47, XXX was similar to 2.5 and similar to 2.9 times higher, respectively, than that in women with 46, XX and similar to 25 and similar to 41 times higher, respectively, than that in men with 46, XY. No statistically significant increase of 47, XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity., Funding Agencies|NIH [AR-062755, AI-024717, AI-031584, AI-062629, AI-063274, AI-082714, AI-083194, AI-101934]; NIH (National Institute of Dental and Craniofacial Research Intramural Research Program); University of Oklahoma Health Sciences Center (Clinical and Translational Science OCTSI Summer Scholar Program); US Department of Veterans Affairs [IMMA9]; US Department of Defense [PR094002]; Alliance for Lupus Research; Kirkland Scholar Program; Strategic Research Program at Helse Bergen; Western Norway Regional Health Authority; Broegelmann Foundation; French Ministry of Health (EvASSESS Programme Hospitalier de Recherche Clinique); Swedish Rheumatism Foundation; Arthritis Australia; Research to Prevent Blindness; Medical Research Council, UK [G0800629]; DFG [KFO 250 WI 1031/6-1]; Canadian Institutes of Health Research [MOP89955, MOP74621]; Ontario Research Fund [RE05-075]; Canada Research Chair Program; Instituto de Salud Carlos III (ISCIII through FEDER) [02558]; Allergan; Lilly; UCB; The NIH [AR-042460, AR-048204, AR-048940, AR-049084, AR-052125, AR-053483, AR-053734, AR-056360, AR-058959, AR-062277, AR-043814, AR-065626, DE-015223, DE-018209, RR-020143, GM-103510, GM-104938, HG-008667, TR-001475, HG-006828]

Published
2016
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19. Induction of Autoimmunity by Multivalent Immunodominant and Subdominant T Cell Determinants of La (SS-B)

Author

Darise Farris, A., Lorena Brown, Pakathip Reynolds, Harley, John B., James, Judith A., Hal Scofield, R., James McCluskey, and Thomas Gordon

Subjects
Immunology, Immunology and Allergy
Abstract

We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa25–44 MAP compared with mice immunized with the 25–44 monomer. Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25–44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa287–301 determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa287–301 peptide. However, immunization with the multivalent mLa287–301 peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa287–301 peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence.

Published
1999

20. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome

Author

Liu, Ke, primary, Kurien, Biji T., additional, Zimmerman, Sarah L., additional, Kaufman, Kenneth M., additional, Taft, Diana H., additional, Kottyan, Leah C., additional, Lazaro, Sara, additional, Weaver, Carrie A., additional, Ice, John A., additional, Adler, Adam J., additional, Chodosh, James, additional, Radfar, Lida, additional, Rasmussen, Astrid, additional, Stone, Donald U., additional, Lewis, David M., additional, Li, Shibo, additional, Koelsch, Kristi A., additional, Igoe, Ann, additional, Talsania, Mitali, additional, Kumar, Jay, additional, Maier‐Moore, Jacen S., additional, Harris, Valerie M., additional, Gopalakrishnan, Rajaram, additional, Jonsson, Roland, additional, Lessard, James A., additional, Lu, Xianglan, additional, Gottenberg, Jacques‐Eric, additional, Anaya, Juan‐Manuel, additional, Cunninghame‐Graham, Deborah S., additional, Huang, Andrew J. W., additional, Brennan, Michael T., additional, Hughes, Pamela, additional, Illei, Gabor G., additional, Miceli‐Richard, Corinne, additional, Keystone, Edward C., additional, Bykerk, Vivian P., additional, Hirschfield, Gideon, additional, Xie, Gang, additional, Ng, Wan‐Fai, additional, Nordmark, Gunnel, additional, Eriksson, Per, additional, Omdal, Roald, additional, Rhodus, Nelson L., additional, Rischmueller, Maureen, additional, Rohrer, Michael, additional, Segal, Barbara M., additional, Vyse, Timothy J., additional, Wahren‐Herlenius, Marie, additional, Witte, Torsten, additional, Pons‐Estel, Bernardo, additional, Alarcón‐Riquelme, Marta E., additional, Guthridge, Joel M., additional, James, Judith A., additional, Lessard, Christopher J., additional, Kelly, Jennifer A., additional, Thompson, Susan D., additional, Gaffney, Patrick M., additional, Montgomery, Courtney G., additional, Edberg, Jeffrey C., additional, Kimberly, Robert P., additional, Alarcón, Graciela S., additional, Langefeld, Carl L., additional, Gilkeson, Gary S., additional, Kamen, Diane L., additional, Tsao, Betty P., additional, Joseph McCune, W., additional, Salmon, Jane E., additional, Merrill, Joan T., additional, Weisman, Michael H., additional, Wallace, Daniel J., additional, Utset, Tammy O., additional, Bottinger, Erwin P., additional, Amos, Christopher I., additional, Siminovitch, Katherine A., additional, Mariette, Xavier, additional, Sivils, Kathy L., additional, Harley, John B., additional, and Hal Scofield, R., additional

Published
2016
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21. The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Author

Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Hal Scofield, R, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Moser Sivils, Kathy L, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, Kaufman, Kenneth M, Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Hal Scofield, R, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Moser Sivils, Kathy L, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, and Kaufman, Kenneth M

Abstract

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

Published
2015
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23. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome

Author

Lessard, Christopher J., Li, He, Adrianto, Indra, Ice, John A., Rasmussen, Astrid, Grundahl, Kiely M., Kelly, Jennifer A., Dozmorov, Mikhail G., Miceli-Richard, Corinne, Bowman, Simon, Lester, Sue, Eriksson, Per, Eloranta, Maija-Leena, Brun, Johan G., Goransson, Lasse G., Harboe, Erna, Guthridge, Joel M., Kaufman, Kenneth M., Kvarnstrom, Marika, Jazebi, Helmi, Cunninghame Graham, Deborah S., Grandits, Martha E., Nazmul-Hossain, Abu N M., Patel, Ketan, Adler, Adam J., Maier-Moore, Jacen S., Darise Farris, A, Brennan, Michael T., Lessard, James A., Chodosh, James, Gopalakrishnan, Rajaram, Hefner, Kimberly S., Houston, Glen D., Huang, Andrew J W., Hughes, Pamela J., Lewis, David M., Radfar, Lida, Rohrer, Michael D., Stone, Donald U., Wren, Jonathan D., Vyse, Timothy J., Gaffney, Patrick M., James, Judith A., Omdal, Roald, Wahren-Herlenius, Marie, Illei, Gabor G., Witte, Torsten, Jonsson, Roland, Rischmueller, Maureen, Ronnblom, Lars, Nordmark, Gunnel, Ng, Wan-Fai, Mariette, Xavier, Anaya, Juan-Manuel, Rhodus, Nelson L., Segal, Barbara M., Hal Scofield, R, Montgomery, Courtney G., Harley, John B., Sivils, Kathy L., Lessard, Christopher J., Li, He, Adrianto, Indra, Ice, John A., Rasmussen, Astrid, Grundahl, Kiely M., Kelly, Jennifer A., Dozmorov, Mikhail G., Miceli-Richard, Corinne, Bowman, Simon, Lester, Sue, Eriksson, Per, Eloranta, Maija-Leena, Brun, Johan G., Goransson, Lasse G., Harboe, Erna, Guthridge, Joel M., Kaufman, Kenneth M., Kvarnstrom, Marika, Jazebi, Helmi, Cunninghame Graham, Deborah S., Grandits, Martha E., Nazmul-Hossain, Abu N M., Patel, Ketan, Adler, Adam J., Maier-Moore, Jacen S., Darise Farris, A, Brennan, Michael T., Lessard, James A., Chodosh, James, Gopalakrishnan, Rajaram, Hefner, Kimberly S., Houston, Glen D., Huang, Andrew J W., Hughes, Pamela J., Lewis, David M., Radfar, Lida, Rohrer, Michael D., Stone, Donald U., Wren, Jonathan D., Vyse, Timothy J., Gaffney, Patrick M., James, Judith A., Omdal, Roald, Wahren-Herlenius, Marie, Illei, Gabor G., Witte, Torsten, Jonsson, Roland, Rischmueller, Maureen, Ronnblom, Lars, Nordmark, Gunnel, Ng, Wan-Fai, Mariette, Xavier, Anaya, Juan-Manuel, Rhodus, Nelson L., Segal, Barbara M., Hal Scofield, R, Montgomery, Courtney G., Harley, John B., and Sivils, Kathy L.

Abstract

Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome., Funding Agencies|NIH|P50 AR06080405P01 AR049084-105P30 AR0534831U01 AI1019345P30 GM103510|Intramural Research Program of the National Institute of Dental and Craniofacial Research||American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award

Published
2013
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24. Prolidase deficiency breaks tolerance to lupus-associated antigens

Author

Kurien, Biji T., primary, D'Sousa, Anil, additional, Bruner, Benjamin F., additional, Gross, Timothy, additional, James, Judith A., additional, Targoff, Ira N., additional, Maier-Moore, Jacen S., additional, Harley, Isaac T. W., additional, Wang, Heng, additional, and Hal Scofield, R., additional

Published
2013
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29. Modification of lupus-associated 60-kDa Ro protein with the lipid oxidation product 4-hydroxy-2-nonenal increases antigenicity and facilitates epitope spreading

Author

Hal Scofield, R., primary, Kurien, Biji T., additional, Ganick, Samantha, additional, McClain, Micah T., additional, Pye, Quentin, additional, James, Judith A., additional, Schneider, Rebecca I., additional, Broyles, Robert H., additional, Bachmann, Michael, additional, and Hensley, Kenneth, additional

Published
2005
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33. Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort.

Author

Lu, Rufei, Robertson, Julie M., Bruner, Benjamin F., Guthridge, Joel M., Neas, Barbara R., Nath, Swapan K., Kelly, Jennifer A., Moser Sivils, Kathy L., Chakravarty, Eliza F., Kamen, Diane L., Gilkeson, Gary S., Wallace, Daniel J., Weisman, Michael H., Hal Scofield, R., Harley, John B., and James, Judith A.

Abstract

Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE) clinical features in a large lupus cohort. Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis. Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP. Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use. [ABSTRACT FROM AUTHOR]

Published
2012
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35. Calcitonin-Secreting Neuroendocrine Carcinoma of Larynx with Metastasis to Thyroid

Author

LaBryer, Lauren, Sawh, Ravindranauth, McLaurin, Colby, and Hal Scofield, R.

Abstract

Primary neuroendocrine tumors of the larynx are rare, with moderately differentiated neuroendocrine carcinoma (MDNC) being the most frequent histologic type. We report a MDNC in a 57-year-old gentleman with an enlarging right-sided neck mass. Flexible fiberoptic exam revealed a right arytenoid lesion. Histology from excisional biopsy was concerning for medullary thyroid carcinoma (MTC) versus NET of the larynx. Immunohistochemistry was diffusely positive for calcitonin and CEA and focally positive for TTF-1. Serum calcitonin was elevated. Thyroid ultrasound was unremarkable. The patient underwent laryngectomy, thyroidectomy, and neck dissection. Pathology showed neuroendocrine carcinoma of right arytenoid with positive cervical lymph nodes. A 4 mm deposit of NET was present in right thyroid with adjacent intravascular tumor consistent with thyroidal metastasis from a primary laryngeal NET (MDNC). MDNC and MTC can be microscopically indistinguishable. Both tumors can stain positively for calcitonin and CEA. TTF-1 staining has been useful to help distinguish these tumors as it is strongly and diffusely positive in MTC, but usually negative (or only focally positive) in MDNC. We report the fourth case of primary neuroendocrine carcinoma of the larynx associated with elevated serum calcitonin level and the first such case associated with metastasis to the thyroid.

Published
2015
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36. Association between Secondary and Primary Sjögren’s Syndrome in a Large Collection of Lupus Families

Author

Aggarwal, Rachna, Anaya, Juan-Manuel, A. Koelsch, Kristi, T. Kurien, Biji, and Hal Scofield, R.

Abstract

Objective. Systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families. Methods. We collected clinical and serological data on 2694 SLE patients, 7390 SLE-unaffected relatives of the SLE patients, and 1470 matched controls. Results. Of the 2694 subjects with SLE, 548 had secondary SS, while 71 of their 7390 SLE-unaffected relatives had primary SS. None of the 1470 controls had SS as defined herein (p=5×10-5 compared to SLE-unaffected relatives). Of the 71 SLE-unaffected relatives with primary SS, 18 (25.3%) had an SLE-affected family member with secondary SS, while only 530 of the 7319 (7.2%) SLE-unaffected relatives without SS did so (p=1×10-8). Conclusion. Among families identified for the presence of SLE, primary and secondary SS tend to occur within the same families. These results highlight the commonalities between these two forms of SS, which in fact correspond to the same disease.

Published
2015
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37. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus

Author

Marta E. Alarcón-Riquelme, Ignacio García-De La Torre, Luis J. Catoggio, Timothy B. Niewold, Ana I. Marcos, Barry I. Freedman, Pilar C. Marino, Marisa Jorfen, Griselda Buchanan, Marcelo Abdala, Anne M. Stevens, Fernando A. Ramos, Emoke Endreffy, Sandra M. Navarro, Ana M. Bertoli, Sergio Migliarese, Jorge Manni, Jose L. Presas, César Graf, László Kovács, Hye jin Jeong, John B. Harley, Berta Martins da Silva, Cesar Caprarulo, Guillermo Tate, Jennifer M. Grossman, Julio Sánchez-Román, Jian Zhao, Javier Martin, Cristina G. Battagliotti, Estela Bertero, Chaim O. Jacob, Carlos E. Perandones, Kenneth M. Kaufman, Guillermo A. Berbotto, Alberto Allievi, John D. Reveille, Sebastian Grimaudo, Estela L. Motta, Susana Gamron, Yeong Wook Song, Mario Cardiel Ríos, José Luis Callejas, Gary S. Gilkeson, Mercedes A. García, Hugo R. Scherbarth, Kathy Moser Sivils, María Francisca González-Escribano, Alejandro Alvarellos, Antonio La Cava, Mariano Cucho, Joan T. Merrill, Carlos D. Santos, Torsten Witte, Cristina Drenkard, R. Hal Scofield, Seung Taek Song, Cristina Prigione, Lindsey A. Criswell, Mariela Bearzotti, Deh Ming Chang, José Mario Sabio, Francisco Caeiro, Mauro Galeazzi, Rosalind Ramsey-Goldman, Simon A. Palatnik, Lennart Truedsson, Marco Maradiaga Ceceña, Johan Frostegård, Susan A. Boackle, Sanatorio Parque, Francisco Moctezuma, Hui Wu, Juan Carlos Marcos, Eduardo Acevedo, Timothy J. Vyse, Jennifer A. Kelly, Michelle Petri, Carlos Vasconcelos, Sandra D'Alfonso, Elizabeth E. Brown, Norberto Ortego-Centeno, Betty P. Tsao, Enrique de Ramón, Juan-Manuel Anaya, Diane L. Kamen, Emilia Menso, Gian Domenico Sebastiani, Patrick M. Gaffney, Judith A. James, Sang Cheol Bae, Susana Roverano, Carolina Guillerón, Jeffrey C. Edberg, Enrique R. Soriano, Carl D. Langefeld, Elisa J. Romero, Alicia Eimon, Bevra H. Hahn, Robert P. Kimberly, Luis M. Vilá, Graciela S. Alarcón, Sergio Paira, Bernard Lauwerys, Zhao, J., Wu, H., Langefeld, C. D., Kaufman, K. M., Kelly, J. A., Bae, S. -C., Alarcon-Riquelme, M. E., Alarcon, G. S., Anaya, J. -M., Criswell, L. A., Freedman, B. I., Kamen, D. L., Gilkeson, G. S., Jacob, C. O., James, J. A., Merrill, J. T., Gaffney, P. M., Sivils, K. M., Niewold, T. B., Petri, M. A., Song, S. T., Jeong, H. -J., Ramsey-Goldman, R., Reveille, J. D., Hal Scofield, R., Stevens, A. M., Boackle, S. A., Vila, L. M., Chang, D. -M., Song, Y. W., Vyse, T. J., Harley, J. B., Brown, E. E., Edberg, J. C., Kimberly, R. P., Hahn, B. H., Grossman, J. M., Tsao, B. P., La Cava, A., Frostegard, J., Truedsson, L., de Ramon, E., Sabio, J. M., Gonzalez-Escribano, M. F., Martin, J., Ortego-Centeno, N., Callejas, J. L., Sanchez-Roman, J., D'Alfonso, S., Migliarese, S., Sebastiani, G. -D., Galeazzi, M., Witte, T., Lauwerys, B. R., Endreffy, E., Kovacs, L., Vasconcelos, C., da Silva, B. M., Scherbarth, H. R., Marino, P. C., Motta, E. L., Gamron, S., Drenkard, C., Menso, E., Allievi, A., Tate, G. A., Presas, J. L., Palatnik, S. A., Abdala, M., Bearzotti, M., Alvarellos, A., Caeiro, F., Bertoli, A., Paira, S., Roverano, S., Graf, C. E., Bertero, E., Caprarulo, C., Buchanan, G., Guilleron, C., Grimaudo, S., Manni, J., Catoggio, L. J., Soriano, E. R., Santos, C. D., Prigione, C., Ramos, F. A., Navarro, S. M., Berbotto, G. A., Jorfen, M., Romero, E. J., Garcia, M. A., Marcos, J. C., Marcos, A. I., Perandones, C. E., Eimon, A., Parque, S., Battagliotti, C. G., Acevedo, E., Cucho, M., de la Torre, I. G., Rios, M. C., Moctezuma, F., and Maradiaga Cecena, M.

Subjects
Leptin, Hispanic, Gene, Dna determination, immune system diseases, Lep gene, Genotype, 2.1 Biological and endogenous factors, Lupus Erythematosus, Systemic, Immunology and Allergy, Medicine, Aetiology, skin and connective tissue diseases, Priority journal, Leptin pathway, Gene polymorphism, Gene polymorphisms, Single Nucleotide, East asian, Case-Control Studie, Human, Lepr gene, Immunology, Case control study, Lupus, Single-nucleotide polymorphism, Major clinical study, Systemic lupus erythematosu, Autoimmune Disease, Polymorphism, Single Nucleotide, Article, European american, Systemic lupus erythematosus, Clinical Research, Genetic susceptibility, Genetics, Genetic predisposition, Humans, Genetic Predisposition to Disease, Genetic Testing, African american, Polymorphism, Genetic risk, Inflammation, Lupus Erythematosus, business.industry, Inflammatory and immune system, Pparg gene, Marta E. Alarcón-Riquelme for the BIOLUPUS and GENLES networks, Systemic, Case-control study, Single nucleotide polymorphism, Case-Control Studies, Multiple comparisons problem, Genetic association, Ghsr gene, business, Controlled study
Abstract

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. © 2015 Elsevier Inc.

Published
2015

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