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Your search keyword '"Hal Scofield, R."' showing total 3 results
Start Over Author "Hal Scofield, R." Topic lupus
3 results on '"Hal Scofield, R."'

1. In vitro modification of solid phase multiple antigenic peptides/autoantigens with 4-hydroxy-2-nonenal (HNE) provide ideal substrates for detection of anti-HNE antibodies and peptide antioxidants

Author

Kurien, Biji T. and Hal Scofield, R.

Subjects
*IMMUNOGLOBULINS, *ANTIGENS, *ENZYME-linked immunosorbent assay, *PROTEINS
Abstract

Abstract: The role of free radicals in protein modification and the importance of anti-4-hydroxy-2-nonenal (HNE) antibodies as marker of HNE-mediated cell toxicity has been well documented. Proteins modified by HNE in vitro, prior to immobilization on ELISA plates, have served as substrates for assaying these antibodies. We found preferential binding of HNE-modified versus unmodified proteins to ELISA plates and this prompted us to seek a more reliable assay. We report a method to HNE-modify any cysteine/histidine/lysine-containing protein or multiple antigenic peptide (MAP) following their immobilization on an ELISA plate. To a set of wells, HNE (200 μM) dissolved in PBS is added and incubated for 4 h, followed by regular ELISA. Since HNE was supplied dissolved in ethanol, PBS with appropriate amount of ethanol added was used as control. For inhibition experiments, HNE is incubated with or without inhibitors and then added to the wells. The commercial anti-HNE serum bound only to HNE-modified antigens. Sera from rabbits and mice immunized with HNE-modified 60 kDa Ro autoantigen preferentially bound the modified antigens. Modification of solid phase antigens in this manner makes assaying anti-HNE antibodies unambiguous. Lengthy dialysis procedures or the use of spin columns that lead to antigen loss becomes unnecessary for the separation of free HNE. We were able to HNE-modify various antigens (BSA, the autoantigens Ro, La and Sm/nRNP, 60 kDa Ro and Sm MAPs) using this procedure. Using MAPs, we confirmed the importance of histidine, lysine and cysteine residues in HNE modification. In addition, this method allowed identification of inhibitors of HNE-modification. We obtained 61%, 70% and 74% inhibition of HNE-modification of solid phase Ro MAP 166 substrate using BSA, Ro MAP 482 and Ro MAP 166, respectively. Glycyl-proline dipeptide and a MAP from the Sm autoantigen (PPPGMRPP) showed 0% inhibition of HNE-modification. [Copyright &y& Elsevier]

Published
2005
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2. 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., Kurien, Biji T., Ganick, Samantha, McClain, Micah T., Pye, Quentin, James, Judith A., Schneider, Rebecca I., Broyles, Robert H., Bachmann, Michael, and Hensley, Kenneth

Subjects
*SYSTEMIC lupus erythematosus, *IMMUNOGLOBULINS, *EPITOPES, *AUTOIMMUNE diseases
Abstract

Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with autoantibodies as a near universal feature of the disease. The Ro ribonucleoprotein particle, composed of a 60-kDa protein noncovalently associated with human cytoplasmic RNA, is the target of antibodies in 25–40% of lupus patients. Purified human 60-kDa Ro was found to be oxidatively modified. Earlier investigations from our laboratory revealed increased oxidative damage in SLE patients. Therefore we hypothesized that oxidation by-products, such as 4-hydroxy-2-nonenal (HNE), could lead to neoantigens like HNE-modified 60-kDa Ro, which could in turn initiate autoimmunity or drive epitope spreading. To test this hypothesis we immunized rabbits with either HNE-modified 60-kDa Ro or the unmodified Ro. Intramolecular epitope spreading within the Ro molecule and intermolecular epitope spreading to La, double-stranded DNA, nRNP, and Sm occurred preferentially in HNE–Ro-immunized animals. Nonspecific anti-HNE antibody, generated by immunization with HNE–keyhole limpet hemocyanin conjugate, did not significantly bind to these autoantigens. These data may suggest a hitherto unappreciated mechanism by which oxidative stress facilitates epitope spreading in SLE. [Copyright &y& Elsevier]

Published
2005
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3. 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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