Search

Your search keyword '"Ainsworth, H C"' showing total 6 results
Start Over Author "Ainsworth, H C"
6 results on '"Ainsworth, H C"'

1. Transancestral mapping and genetic load in systemic lupus erythematosus

Author

Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, Pineau, Christian A., National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, and Genentech Foundation

Subjects
skin and connective tissue diseases
Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., We gratefully acknowledge the Alliance for Lupus Research for funding and support. The research was supported in part by awards from the Arthritis Research UK Special Strategic Award (ref. 19289) and from George Koukis (T.J.V.). In addition, the research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London (T.J.V.). The work would not be possible without funding from the NIH grants AR049084 (RPK, EEB); the International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) AI083194 (J.B.H.); CA141700, AR058621 Proyecto de Excelencia, Consejeria de Andalucia (M.E.A.R.); AR043814 and AR-065626 (B.P.T.); AR060366, MD007909, AI107176 (S.K.N.); AR-057172 (C.O.J.); RC2 AR058959, U19 A1082714, R01 AR063124, P30 GM110766, R01 AR056360 (P.M.G.); P60 AR053308 (L.A.C.), MUSC part is from UL1RR029882 (G.S.G., D.L.K.) and 5P60AR062755 (G.S.G., D.L.K., P.R.R.). Oklahoma Samples U19AI082714, U01AI101934, P30GM103510, U54GM104938 and P30AR053483 (J.A.J., J.M.G.); Northwestern P60 AR066464 and 1U54TR001018 (R.R.G.); This study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) under Award Numbers K01 AR067280 and P60 AR062755 (PSR); N01AR22265 (funded collection of APPLE samples) (LES) and the APPLE Investigators; R01AR43727, NIH AR 043727 and 069572 (M.P.); NIAMS/NIH P50-AR055503 (D.R.K.). We would like to also thank the RILITE foundation for financial support (C.D.L.). Additional funding for Immunochip genotyping was provided by Genentech.

Published
2017

2. Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

Author

Hinks, Anne, Bowes, John, Cobb, Joanna, Ainsworth, H. C., Marion, M. C., Comeau, M. E., Han, B., Becker, M. L., Bohnsack, J. F., de Bakker, P. I. W., Haas, J. P., Hazen, M., Lovell, D. J., Nigrovic, P. A., Nordal, E., Punnaro, M., Rosenberg, A. M., Rygg, M., Smith, Samantha, Wise, C. A., Videm, V., Wedderburn, L. R., Yarwood, Annie, Yeung, R. S. M., Prahalad, S., Langefeld, C. D., Raychaudhuri, Soumya, Thompson, S. D., and Thomson, Wendy

Subjects
musculoskeletal diseases, Juvenile idiopathic arthritis (JIA), Autoimmune disease, Rheumatoid arthritis, Gene polymorphism, genetic structures, skin and connective tissue diseases
Abstract

Objectives:Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leukocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods:Dense genotype data from the HLA region, from the Immunochip array for 5,043 JIA cases and 14,390 controls, was used to impute SNPs, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.ResultsWe identified category-specific associations and have demonstrated for the first time that rheumatoid factor negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. ConclusionsThe findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and etiology and facilitate transition from paediatric to adult services.

Published
2017
Full Text
View/download PDF

3. Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

Author

Hinks, A, Bowes, J, Cobb, J, Ainsworth, H C, Marion, M C, Comeau, M E, Sudman, M, Han, B, Becker, M L, Bohnsack, J F, de Bakker, P I W, Haas, J P, Hazen, M, Lovell, D J, Nigrovic, P A, Nordal, E, Punnaro, M, Rosenberg, A M, Rygg, M, Smith, S L, Wise, C A, Videm, V, Wedderburn, L R, Yarwood, A, Yeung, R S M, Prahalad, S, Langefeld, C D, Raychaudhuri, S, Thompson, S D, and Thomson, W

Subjects
Adult, musculoskeletal diseases, Genotype, genetic structures, Rheumatoid Arthritis, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Rheumatology: 759, Polymorphism, Single Nucleotide, Arthritis, Juvenile, Autoimmune Diseases, Arthritis, Rheumatoid, Major Histocompatibility Complex, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Reumatologi: 759, Gene Polymorphism, HLA Antigens, Rheumatoid Factor, Case-Control Studies, Humans, Amino Acids, Juvenile Idiopathic Arthritis, Child, skin and connective tissue diseases, Basic and Translational Research, Alleles, HLA-DRB1 Chains
Abstract

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. Methods Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. Results We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. Conclusions The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

Published
2016

4. Transancestral mapping and genetic load in systemic lupus erythematosus

Author

National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, Genentech Foundation, Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, Pineau, Christian A., National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, Genentech Foundation, Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, and Pineau, Christian A.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

Published
2017

6. Salivary dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus.

Author

Clancy RM, Marion MC, Ainsworth HC, Blaser MJ, Chang M, Howard TD, Izmirly PM, Lacher C, Masson M, Robins K, Buyon JP, and Langefeld CD

Subjects
Adult, Amino Acid Sequence, Autoantibodies immunology, Autoimmunity, Biodiversity, Female, HLA Antigens immunology, Humans, Infant, Newborn, Lupus Erythematosus, Systemic etiology, Lupus Erythematosus, Systemic metabolism, Lupus Erythematosus, Systemic therapy, Male, Microbiota, Peptides chemistry, Peptides immunology, Pregnancy, Young Adult, Antibodies, Antinuclear immunology, Dysbiosis, Lupus Erythematosus, Systemic congenital, Prenatal Exposure Delayed Effects, Salivary Glands microbiology
Abstract

Mothers giving birth to children with manifestations of neonatal lupus (NL) represent a unique population at risk for the development of clinically evident pathologic autoimmunity since many are asymptomatic and only become aware of anti-SSA/Ro positivity (anti-Ro+) based on heart block in their fetus. Accordingly, we hypothesized that the microbiome in saliva is associated with the development of autoreactivity and in some cases the progression in health status from benign to overt clinical disease including Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The study comprised a clinical spectrum of anti-Ro+ mothers, all of whom gave birth to a child with NL: 9 were asymptomatic or had an undifferentiated autoimmune disease (Asym/UAS) and 16 fulfilled criteria for SS and/or SLE. Microbial diversity was reduced across all levels from kingdom to species for the anti-Ro+ mothers vs healthy controls; however, there were no significant differences between Asym/UAS and SS/SLE mothers. Relative abundance of Proteobacteria and more specifically class Betaproteobacteria decreased with clinical severity (healthy controls < Asym/UAS < SS/SLE). These ordered differences were maintained through the taxonomic hierarchy to three genera (Lautropia, Comamonas, and Neisseria) and species within these genera (L. mirabilis, N. flavescens and N. oralis). Biometric analysis comparing von Willebrand Factor domains present in human Ro60 with L. mirabilis proteins support the hypothesis of molecular mimicry. These data position the microbiome in the development of anti-Ro reactivity and subsequent clinical spectrum of disease., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results