13 results on '"Radfar, A."'
Search Results
2. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögrenʼs Syndrome
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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, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Illei, Gabor G., Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Segal, Barbara M., Vyse, Timothy J., Wahren-Herlenius, Marie, Witte, Torsten, Pons-Estel, Bernardo, Alarcón-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., Alarcón, Graciela S., Langefeld, Carl L., Gilkeson, Gary S., Kamen, Diane L., Tsao, Betty P., McCune, Joseph W., Salmon, Jane E., Merrill, Joan T., Weisman, Michael H., Wallace, Daniel J., Utset, Tammy O., Bottinger, Erwin P., Amos, Christopher I., Siminovitch, Katherine A., Mariette, Xavier, Sivils, Kathy L., Harley, John B., and Scofield, Hal R.
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- 2016
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3. Brief Report: Patients With Primary Sjögrenʼs Syndrome Who Are Positive for Autoantibodies to Tripartite Motif–Containing Protein 38 Show Greater Disease Severity
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Wolska, Nina, Rybakowska, Paulina, Rasmussen, Astrid, Brown, Michael, Montgomery, Courtney, Klopocki, Arkadiusz, Grundahl, Kiely, Scofield, Robert H., Radfar, Lida, Stone, Donald U., Anaya, Juan M., Ice, John A., Lessard, Christopher J., Lewis, David M., Rhodus, Nelson L., Gopalakrishnan, Rajaram, Huang, Andrew J. W., Hughes, Pamela J., Rohrer, Michael D., Weisman, Michael H., Venuturupalli, Swamy, Guthridge, Joel M., James, Judith A., Sivils, Kathy L., Bagavant, Harini, and Deshmukh, Umesh S.
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- 2016
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4. Antibody-Secreting Cell Specificity in Labial Salivary Glands Reflects the Clinical Presentation and Serology in Patients With Sjögrenʼs Syndrome
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Maier-Moore, Jacen S., Koelsch, Kristi A., Smith, Kenneth, Lessard, Christopher J., Radfar, Lida, Lewis, David, Kurien, Biji T., Wolska, Nina, Deshmukh, Umesh, Rasmussen, Astrid, Sivils, Kathy L., James, Judith A., Farris, Darise A., and Scofield, Hal R.
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- 2014
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5. Interaction Between Innate Immunity and Anti-Ro52 Antibodies is Critical for the Induction of Sjogrenʼs Syndrome-like Disease in Mice.: 1798
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Kaplonek, Paulina, Szczerba, Barbara, Wolska, Nina, Rybakowska, Paulina, Klopocki, Arkadiusz, Dey, Paromita, Rasmussen, Astrid, Hefner, Kimberly, Young, Stephen, Stone, Donald U., Lewis, David M., Radfar, Lida, Scofield, Hal R., Sivils, Kathy Moser, Bagavant, Harini, and Deshmukh, Umesh
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- 2014
6. Genome-Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögrenʼs Syndrome
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Altorok, Nezam, Coit, Patrick, Hughes, Travis, Koelsch, Kristi A., Stone, Donald U., Rasmussen, Astrid, Radfar, Lida, Scofield, Hal R., Sivils, Kathy L., Farris, Darise A., and Sawalha, Amr H.
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- 2014
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7. Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N -Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren’s Syndrome
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Syed M. Quadri, Kathy L. Sivils, Lida Radfar, Judith A. James, Kristi A. Koelsch, A. Darise Farris, Astrid Rasmussen, Teresa Scordino, Biji T. Kurien, R. Hal Scofield, Kenneth J. Smith, Christopher J. Lessard, Jacen S. Moore, C. Erick Kaufman, Sylvain Lehoux, Nan Jia, Joshua W. Cavett, Richard D. Cummings, Tim Mather, and David M Lewis
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0301 basic medicine ,medicine.drug_class ,Immunology ,Autoantibody ,Somatic hypermutation ,Biology ,Monoclonal antibody ,Molecular biology ,law.invention ,03 medical and health sciences ,030104 developmental biology ,Germline mutation ,Rheumatology ,law ,biology.protein ,Recombinant DNA ,medicine ,Immunology and Allergy ,Antibody ,Framework region ,Gene - Abstract
Objective To better understand the role of B cells, the potential mechanisms responsible for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjogren's syndrome (SS), this study explored patterns of selection pressure and sites of N-glycosylation acquired by somatic mutation (acN-glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated from the minor salivary glands of patients with SS and non-SS control patients with sicca symptoms. Methods A novel method to produce and characterize recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates was applied to concurrently probe expressed genes (all heavy- and light-chain isotypes as well as any other gene of interest not related to immunoglobulin) in the labial salivary glands of patients with SS and non-SS controls. V regions were amplified by reverse transcription-polymerase chain reaction, sequenced, and analyzed for the incidence of N-glycosylation and selection pressure. For specificity testing, the amplified regions were expressed as either the native mAb or mutant mAb lacking the acN-glyc motif. Protein modeling was used to demonstrate how even an acN-glyc site outside of the complementarity-determining region could participate in, or inhibit, antigen binding. Results V-region sequence analyses revealed clonal expansions and evidence of secondary light-chain editing and allelic inclusion, of which neither of the latter two have previously been reported in patients with SS. Increased frequencies of acN-glyc were found in the sequences from patients with SS, and these acN-glyc regions were associated with an increased number of replacement mutations and lowered selection pressure. A clonal set of polyreactive mAb with differential framework region 1 acN-glyc motifs was also identified, and removal of the acN-glyc could nearly abolish binding to autoantigens. Conclusion These findings support the notion of an alternative mechanism for the selection and proliferation of some autoreactive B cells, involving V-region N-glycosylation, in patients with SS.
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- 2018
8. Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity
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Harini Bagavant, Courtney G. Montgomery, Paulina Rybakowska, Juan-Manuel Anaya, Umesh S. Deshmukh, Lida Radfar, Rajaram Gopalakrishnan, Nelson L. Rhodus, Arkadiusz G. Klopocki, John A. Ice, Donald U. Stone, Pamela J. Hughes, Michael H. Weisman, Nina Wolska, Kiely Grundahl, Michael Brown, R. H. Scofield, Judith A. James, Michael D. Rohrer, Christopher J. Lessard, Andrew J.W. Huang, Joel M. Guthridge, Kathy L. Sivils, David M Lewis, Swamy Venuturupalli, and Astrid Rasmussen
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030203 arthritis & rheumatology ,0301 basic medicine ,medicine.diagnostic_test ,biology ,Immunology ,Autoantibody ,Hypergammaglobulinemia ,medicine.disease ,Tripartite motif family ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,Biopsy ,medicine ,biology.protein ,Immunology and Allergy ,Rheumatoid factor ,Clinical significance ,Antibody ,Anti-SSA/Ro autoantibodies - Abstract
Objective Autoantibodies reactive with Ro52 (tripartite motif−containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjogren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease. Methods Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro−transcribed and −translated 35S-methionine−labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21. Results TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ≥3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128–238) and the B30.2/SPRY (amino acids 268–465) domains on TRIM38. Affinity-purified antibodies to TRIM38–CortBP-2 and TRIM38–B30.2/SPRY domains reacted with TRIM21. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.
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- 2016
9. Brief Report: Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome
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Kaustubh S. Chaudhari, Marta E. Alarcón-Riquelme, Lida Radfar, Ke Liu, Michael H. Weisman, Roland Jonsson, Ilias Alevizos, Xianglan Lu, Edward C. Keystone, Gideon M. Hirschfield, Deborah S. Cunninghame-Graham, Roald Omdal, Nelson L. Rhodus, Andrew J.W. Huang, Swamy Venuturupalli, Daniel J. Wallace, Anum Fayaaz, Torsten Witte, Valerie M. Harris, Astrid Rasmussen, Vivian P. Bykerk, Kathy L. Sivils, John B. Harley, Maureen Rischmueller, Barbara M. Segal, Shibo Li, Marie Wahren-Herlenius, Xavier Mariette, Jacques-Eric Gottenberg, Joshua W. Cavett, Jennifer A. Kelly, Donald U. Stone, Sara Magnusson Bucher, R. Hal Scofield, Juan-Manuel Anaya, David Lewis, Pamela J. Hughes, Corinne Miceli-Richard, Christopher J. Lessard, Per Eriksson, Biji T. Kurien, Rohan Sharma, Michael T. Brennan, Bernardo A. Pons-Estel, Michael D. Rohrer, Kristi A. Koelsch, Wan-Fai Ng, Gunnel Nordmark, and C. Erick Kaufman
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030203 arthritis & rheumatology ,0301 basic medicine ,Lupus erythematosus ,Immunology ,Karyotype ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Rheumatology ,Polymorphism (computer science) ,Turner syndrome ,medicine ,Immunology and Allergy ,Allele ,Trisomy ,X chromosome - Abstract
Background. Sjogren's syndrome and systemic lupus erythematosus (SLE) are related by clinical and serological manifestations as well as genetic risks. Both diseases are more commonly found in women compared to men at a ratio of about 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 Sjogren's syndrome or SLE patients with intensity plots of X chromosome single nucleotide polymorphism (SNP) alleles along with karyotype of selected subjects. Results. Among ∼2500 women with SLE we found three patients with a triple mosaic consisting of 45,X/46,XX/47,XXX. Among ∼2100 women with Sjogren's syndrome, one 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 were found among controls. In another Sjogren's cohort, we found a mother-daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in approximately 1 in 25,000 to 50,000 live female births, while partial triplications such are even rarer. Conclusions. Very rare X chromosome abnormalities are present among patients with either Sjogren's or SLE, and may inform the location of a gene(s) that mediate an X dose effect as well as critical cell types in which such effect is operative. This article is protected by copyright. All rights reserved.
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- 2017
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10. Genome-Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome
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Travis K. Hughes, Patrick Coit, Lida Radfar, R. Hal Scofield, Kathy L. Sivils, Astrid Rasmussen, Nezam Altorok, Amr H. Sawalha, Donald U. Stone, A. Darise Farris, and Kristi A. Koelsch
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biology ,Immunology ,Bisulfite sequencing ,CD247 ,PTPRC ,Rheumatology ,CpG site ,DNA methylation ,Cancer research ,biology.protein ,Immunology and Allergy ,Epigenetics ,Transcription Factor Gene ,Gene - Abstract
Objective Primary Sjogren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS. Methods A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicity-matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array, and the data were validated using bisulfite sequencing. Results Genome-wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. Conclusion This is the first epigenome-wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease-associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
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- 2014
11. Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N -Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren’s Syndrome
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Koelsch, Kristi A., primary, Cavett, Joshua, additional, Smith, Kenneth, additional, Moore, Jacen S., additional, Lehoux, Sylvain D., additional, Jia, Nan, additional, Mather, Tim, additional, Quadri, Syed M. S., additional, Rasmussen, Astrid, additional, Kaufman, C. Erick, additional, Lewis, David M., additional, Radfar, Lida, additional, Scordino, Teresa A., additional, Lessard, Christopher J., additional, Kurien, Biji T., additional, Cummings, Richard D., additional, James, Judith A., additional, Sivils, Kathy L., additional, Farris, A. Darise, additional, and Scofield, R. Hal, additional
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- 2018
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12. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome
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Daniel J. Wallace, Wan-Fai Ng, Carrie A. Weaver, Maureen Rischmueller, Marie Wahren-Herlenius, Michael T. Brennan, Gideon M. Hirschfield, Christopher I. Amos, James Chodosh, Michael D. Rohrer, Susan D. Thompson, Katherine A. Siminovitch, Jeffrey C. Edberg, Torsten Witte, Timothy J. Vyse, Barbara M. Segal, Courtney G. Montgomery, Gunnel Nordmark, Valerie M. Harris, Jacen S. Maier-Moore, Judith A. James, Gabor G. Illei, Juan-Manuel Anaya, Tammy O. Utset, Lida Radfar, Ke Liu, Marta E. Alarcón-Riquelme, Diane L. Kamen, W. Joseph McCune, Roald Omdal, Pamela J. Hughes, Kristi A. Koelsch, Corinne Miceli-Richard, Patrick M. Gaffney, Vivian P. Bykerk, Per Eriksson, James A. Lessard, Edward C. Keystone, John B. Harley, Biji T. Kurien, Rajaram Gopalakrishnan, Jennifer A. Kelly, Robert P. Kimberly, Xianglan Lu, Adam Adler, Leah C. Kottyan, Erwin P. Bottinger, Graciela S. Alarcón, Betty P. Tsao, Sara Lazaro, Kenneth M. Kaufman, Joel M. Guthridge, Kathy L. Sivils, C. Langefeld, Michael H. Weisman, Diana H. Taft, Jay Kumar, Joan T. Merrill, R. Hal Scofield, Shibo Li, Nelson L. Rhodus, Xavier Mariette, Jacques-Eric Gottenberg, Gang Xie, Mitali Talsania, Ann Igoe, Christopher J. Lessard, Sarah L. Zimmerman, Bernardo A. Pons-Estel, Gary S. Gilkeson, Roland Jonsson, John A. Ice, Donald U. Stone, Deborah S. Cunninghame-Graham, Jane E. Salmon, Andrew J.W. Huang, David M Lewis, and Astrid Rasmussen
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medicine.medical_specialty ,Sarcoidosis ,Sex Chromosome Disorders of Sex Development ,Immunology ,Gene Dosage ,Trisomy ,medicine.disease_cause ,Gastroenterology ,Article ,Autoimmune Diseases ,Autoimmunity ,Arthritis, Rheumatoid ,Primary biliary cirrhosis ,Rheumatology ,Internal medicine ,Prevalence ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Sex Distribution ,In Situ Hybridization, Fluorescence ,Sex Chromosome Aberrations ,Chromosomes, Human, X ,Lupus erythematosus ,Liver Cirrhosis, Biliary ,business.industry ,Case-control study ,Odds ratio ,medicine.disease ,3. Good health ,Sjogren's Syndrome ,Case-Control Studies ,Rheumatoid arthritis ,Female ,business ,Anti-SSA/Ro autoantibodies - 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 ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjogren's 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 ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼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.
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- 2015
13. Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome.
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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., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons‐Estel, Bernardo, and Jonsson, Roland
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CHROMOSOME abnormalities ,GENETIC polymorphisms ,LONGITUDINAL method ,SJOGREN'S syndrome ,SYSTEMIC lupus erythematosus ,GENETICS - Abstract
Objective Sjögren's 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 ~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 ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46, XX/47, XXX. Among ~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 ~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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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