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2. Drug Therapy

Author

Herrick, Ariane L., Wigley, Fredrick M., Pope, Janet, Wigley, Fredrick M., editor, Herrick, Ariane L., editor, and Flavahan, Nicholas A., editor

Published
2024
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4. Overlooked Manifestations

Author

Shah, Ami A., Wigley, Fredrick M., Allanore, Yannick, editor, Varga, John, editor, Denton, Christopher P., editor, Kuwana, Masataka, editor, Chung, Lorinda, editor, and Shah, Ami A., editor

Published
2024
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7. Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma

Author

Tiniakou, Eleni, Fava, Andrea, McMahan, Zsuzsanna H, Guhr, Tara, O'Meally, Robert N, Shah, Ami A, Wigley, Fredrick M, Cole, Robert N, Boin, Francesco, and Darrah, Erika

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Prevention, Autoimmune Disease, Scleroderma, Rare Diseases, Lung, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adult, Alleles, Autoantibodies, Autoantigens, CD4-Positive T-Lymphocytes, DNA Topoisomerases, Type I, Dendritic Cells, Epitopes, T-Lymphocyte, Female, HLA-DRB1 Chains, Humans, Lung Diseases, Interstitial, Lymphocyte Activation, Male, Peptides, Scleroderma, Systemic, Severity of Illness Index, Clinical Sciences, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveAutoimmune responses to DNA topoisomerase I (topo I) are found in a subset of scleroderma patients who are at high risk for interstitial lung disease (ILD) and mortality. Anti-topo I antibodies (ATAs) are associated with specific HLA-DRB1 alleles, and the frequency of HLA-DR-restricted topo I-specific CD4+ T cells is associated with the presence, severity, and progression of ILD. Although this strongly implicates the presentation of topo I peptides by HLA-DR in scleroderma pathogenesis, the processing and presentation of topo I has not been studied.MethodsWe developed a natural antigen processing assay (NAPA) to identify putative CD4+ T cell epitopes of topo I presented by monocyte-derived dendritic cells (mo-DCs) from 6 ATA-positive patients with scleroderma. Mo-DCs were pulsed with topo I protein, HLA-DR-peptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD4+ T cell activation in 11 ATA-positive and 11 ATA-negative scleroderma patients.ResultsWe found that a common set of 10 topo I epitopes was presented by Mo-DCs from scleroderma patients with diverse HLA-DR variants. Sequence analysis revealed shared peptide-binding motifs within the HLA-DRβ chains of ATA-positive patients and a subset of topo I epitopes with distinct sets of anchor residues capable of binding to multiple different HLA-DR variants. The NAPA-derived epitopes elicited robust CD4+ T cell responses in 73% of ATA-positive patients (8 of 11), and the number of epitopes recognized correlated with ILD severity (P = 0.025).ConclusionThese findings mechanistically implicate the presentation of a convergent set of topo I epitopes in the development of scleroderma.

Published
2020

8. HLA and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Author

Gourh, Pravitt, Safran, Sarah A, Alexander, Theresa, Boyden, Steven E, Morgan, Nadia D, Shah, Ami A, Mayes, Maureen D, Doumatey, Ayo, Bentley, Amy R, Shriner, Daniel, Domsic, Robyn T, Medsger, Thomas A, Ramos, Paula S, Silver, Richard M, Steen, Virginia D, Varga, John, Hsu, Vivien, Saketkoo, Lesley Ann, Schiopu, Elena, Khanna, Dinesh, Gordon, Jessica K, Kron, Brynn, Criswell, Lindsey A, Gladue, Heather, Derk, Chris T, Bernstein, Elana J, Bridges, S Louis, Shanmugam, Victoria K, Kolstad, Kathleen D, Chung, Lorinda, Kafaja, Suzanne, Jan, Reem, Trojanowski, Marcin, Goldberg, Avram, Korman, Benjamin D, Steinbach, Peter J, Chandrasekharappa, Settara C, Mullikin, James C, Adeyemo, Adebowale, Rotimi, Charles, Wigley, Fredrick M, Kastner, Daniel L, Boin, Francesco, and Remmers, Elaine F

Subjects
Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Clinical Research, Scleroderma, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Black or African American, Alleles, Amino Acid Sequence, Antigens, Viral, Autoantibodies, Autoantigens, Computational Biology, Datasets as Topic, Female, Genetic Predisposition to Disease, HLA Antigens, Humans, Male, Mimiviridae, Molecular Mimicry, Phycodnaviridae, Protein Structure, Secondary, Risk Assessment, Scleroderma, Systemic, Sequence Homology, Amino Acid, White People, scleroderma, HLA, autoantibodies, molecular mimicry, mimivirus
Abstract

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10-6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/β allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc.

Published
2020

10. List Of Contributors

Author

Abraham, Roshini Sarah, primary, Afzali, Behdad, additional, Águeda, Ana, additional, Akin, Cem, additional, Albanesi, Cristina, additional, Antiochos, Brendan, additional, Aranow, Cynthia, additional, Atkinson, John P., additional, Aune, Thomas M., additional, Babu, Subash, additional, Balko, Justin, additional, Ballow, Mark, additional, Bean, Rachel, additional, Belavgeni, Alexia, additional, Berek, Claudia, additional, Beukelman, Timothy, additional, Beziat, Vivien, additional, Bimler, Lynn, additional, Andrew Bird, J., additional, Blutt, Sarah E., additional, Boguniewicz, Mark, additional, Boisson, Bertrand, additional, Boisson-Dupuis, Stéphanie, additional, Borzova, Elena, additional, Bottazzi, Maria, additional, Boyaka, Prosper N., additional, Bridges, John, additional, Browne, Sarah K., additional, Burks, A. Wesley, additional, Bustamante, Jacinta, additional, Casanova, Jean-Laurent, additional, Chan, Alice, additional, Chan, Edwin S.L., additional, Chatham, Walter Winn, additional, Chinen, Javier, additional, Christopher-Stine, Lisa, additional, Coates, Emily, additional, Cope, Andrew P., additional, Corry, David B., additional, Cosme, Joana, additional, Cron, Randy Q., additional, Dalakas, Marinos C., additional, Dann, Sara M., additional, Das, Satya, additional, Daughety, Molly M., additional, Diamond, Betty, additional, Dispenzieri, Angela, additional, Durham, Stephen R., additional, Eagar, Todd N., additional, Al-Hosni, Michelle, additional, Elitzur, Sarah, additional, Elmets, Craig A., additional, Erkan, Doruk, additional, Fleisher, Thomas A., additional, Fonacier, Luz, additional, Fontenot, Andrew P., additional, Fragoulis, George, additional, Francischetti, Ivo M.B., additional, Freiwald, Tilo, additional, Frew, Anthony J., additional, Fujihashi, Kohtaro, additional, Gadina, Massimo, additional, Gapin, Laurent, additional, Gatt, Moshe E., additional, Gershwin, M. Eric, additional, Gillespie, Susan L., additional, Gordon, Lynn K., additional, Goronzy, Jörg J., additional, Grattan, Clive E., additional, Greenspan, Neil S., additional, Gschwend, Anna, additional, Gustafson, Claire E., additional, Hackett, Tillie-Louise, additional, Hamilton, Robert G., additional, Happe, Myra, additional, Harrison, Leonard C., additional, Helbling, Arthur, additional, Heckmann, Emmaline, additional, Hogquist, Kristin, additional, Hohl, Tobias M., additional, Holland, Steven M., additional, Hotez, Peter J., additional, Houser, Katherine, additional, Huntingdon, Nicholas D., additional, Hwangpo, Tracy, additional, Izraeli, Shai, additional, Jaffe, Elaine S., additional, Jalkanen, Sirpa, additional, Java, Anuja, additional, Johnson, Douglas B., additional, Johnson, Tory, additional, Jordan, Michael B., additional, Joshi, Shyam R., additional, Jouanguy, Emmanuelle, additional, Kaminski, Henry J., additional, Kaufmann, Stefan H.E., additional, Khan, David A., additional, Kheradmand, Farrah, additional, Khokar, Dilawar Singh, additional, Khoury, Paneez, additional, Klein, Bruce S., additional, Klion, Amy D., additional, Kohn, Donald B., additional, Kono, Michihito, additional, Korngold, Robert, additional, Koulouri, Vasiliki, additional, Kuhns, Douglas B., additional, Kulkarni, Hrishikesh S., additional, Kuo, Caroline Y., additional, Kusner, Linda L., additional, Lahouti, Arash, additional, Lane, Laura C., additional, Laurence, Arian, additional, Lee, Joyce S., additional, Lee, S. Thera, additional, Leung, Donald Y.M., additional, Levy, Ofer, additional, Lewis, Dorothy E., additional, Li, Evan, additional, Libby, Peter, additional, Lichtman, Andrew H., additional, Linkermann, Andreas, additional, Lionakis, Michail S., additional, Liszewski, M. Kathryn, additional, Lockshin, Michael D., additional, Priel, Debra Long, additional, Lorenz, Adi Zoref, additional, Ludwig, Ralf J., additional, Luong, Amber, additional, Luqmani, Raashid Ahmed, additional, Mackay, Meggan, additional, Mahr, Alfred, additional, Malley, Tamir, additional, Mannon, Elinor C., additional, Mannon, Peter J., additional, Mannon, Roslyn B., additional, Manns, Michael P., additional, Maresso, Anthony, additional, Matson, Scott M., additional, Mavragani, Clio P., additional, Maynard, Craig L., additional, McDonald, Douglas, additional, Meylan, Françoise, additional, Miller, Stephen D., additional, Mitchell, Anna L., additional, Monos, Dimitri S., additional, Mueller, Scott N., additional, Mulders-Manders, Catharina M., additional, Munshi, Pashna N., additional, Murphy, Philip M., additional, Noel, Pierre, additional, Notarangelo, Luigi D., additional, Nunes-Santos, Cristiane J., additional, Nussbaum, Robert L., additional, Nutman, Thomas B., additional, Nutt, Stephen L., additional, O'Neill, Lorraine, additional, O'Shea, John J., additional, Ortel, Thomas L., additional, Pai, Sung-Yun, additional, Paul, Mary E., additional, Pearce, Simon, additional, Peterson, Erik J., additional, Pittaluga, Stefania, additional, Polverino, Francesca, additional, Puck, Jennifer M., additional, Puel, Anne, additional, Radbruch, Andreas, additional, Rajalingam, Raja, additional, Reece, Stephen T., additional, Reveille, John D., additional, Rich, Robert R., additional, Ridley, Lauren K., additional, Romeo, Andrew R., additional, Rooney, Cliona M., additional, Rosen, Antony, additional, Rosenzweig, Sergio, additional, Rouse, Barry T., additional, Rowley, Scott D., additional, Sahiner, Umit Murat, additional, Sakaguchi, Shimon, additional, Salinas, Whitney, additional, Salmi, Marko, additional, Satola, Sarah, additional, Schechter, Marcos, additional, Schmidt, Enno, additional, Schroeder, Harry W., additional, Schwartzberg, Pamela L., additional, Sciumè, Giuseppe, additional, Segal, Benjamin M., additional, Selmi, Carlo, additional, Sharabi, Amir, additional, Shimano, Kristin Ammon, additional, Sikorski, Patricia M., additional, Simon, Anna, additional, Smith, Gideon P., additional, Song, Joo Y., additional, Stephens, David S., additional, Stephens, Robin, additional, Sun, Michel M., additional, Beretta-Piccoli, Benedetta Terziroli, additional, Tonnus, Wulf, additional, Torgerson, Troy R., additional, Torres, Raul Martin, additional, Treat, Jennifer D., additional, Tsokos, George C., additional, Uzel, Gülbü, additional, Uzonna, Jude E., additional, van der Hilst, Jeroen C.H., additional, van der Meer, Jos W.M., additional, Varga, John, additional, Waldman, Meryl, additional, Weatherhead, Jill, additional, Weiser, Peter, additional, Weyand, Cornelia M., additional, Wigley, Fredrick M., additional, Wing, James B., additional, Wood, Kathryn J., additional, Wilde, Shyra, additional, Xu, Hui, additional, Yusuf, Nabiha, additional, Zerbe, Christa S., additional, Zhang, Qian, additional, Ben-Yehuda, Dina, additional, Zhang, Shen-Ying, additional, and Zieske, Arthur W., additional

Published
2023
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11. Clinical and serological features of systemic sclerosis in a multicenter African American cohort

Author

Morgan, Nadia D, Shah, Ami A, Mayes, Maureen D, Domsic, Robyn T, Medsger, Thomas A, Steen, Virginia D, Varga, John, Carns, Mary, Ramos, Paula S, Silver, Richard M, Schiopu, Elena, Khanna, Dinesh, Hsu, Vivien, Gordon, Jessica K, Gladue, Heather, Saketkoo, Lesley A, Criswell, Lindsey A, Derk, Chris T, Trojanowski, Marcin A, Shanmugam, Victoria K, Chung, Lorinda, Valenzuela, Antonia, Jan, Reem, Goldberg, Avram, Remmers, Elaine F, Kastner, Daniel L, Wigley, Fredrick M, Gourh, Pravitt, and Boin, Francesco

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Autoimmune Disease, Rare Diseases, Scleroderma, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Inflammatory and immune system, Adult, Black or African American, Chromosome Mapping, Cohort Studies, Cross-Sectional Studies, Databases, Factual, Female, Humans, Male, Prevalence, Prospective Studies, Retrospective Studies, Scleroderma, Systemic, Severity of Illness Index, Socioeconomic Factors, United States, African Americans, autoantibodies, systemic sclerosis
Abstract

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry.

Published
2017

14. Overlooked Manifestations

Author

Lally, Edward V., Shah, Ami A., Wigley, Fredrick M., Varga, John, editor, Denton, Christopher P., editor, Wigley, Fredrick M., editor, Allanore, Yannick, editor, and Kuwana, Masataka, editor

Published
2017
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19. Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course

Author

Kim, Ji Soo, primary, Woods, Adrianne, additional, Gutierrez‐Alamillo, Laura, additional, Laffoon, Maureen, additional, Wigley, Fredrick M., additional, Hummers, Laura K., additional, Rosen, Antony, additional, Zeger, Scott, additional, Domsic, Robyn T., additional, Casciola‐Rosen, Livia, additional, and Shah, Ami A., additional

Published
2023
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24. Anti‐Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.

Author

McMahan, Zsuzsanna H., Kulkarni, Subhash, Andrade, Felipe, Perin, Jamie, Zhang, Chengxiu, Hooper, Jody E., Wigley, Fredrick M., Rosen, Antony, Pasricha, Pankaj J., and Casciola‐Rosen, Livia

Subjects
AUTOANTIBODIES, AUTONOMIC nervous system, IN vivo studies, STAINS & staining (Microscopy), ANALYSIS of variance, CONSTIPATION, IMMUNOHISTOCHEMISTRY, SYSTEMIC scleroderma, GASTROINTESTINAL diseases, PRECIPITIN tests, REGRESSION analysis, MANN Whitney U Test, RADIONUCLIDE imaging, IMMUNOBLOTTING, T-test (Statistics), MASS spectrometry, ENZYME-linked immunosorbent assay, FLUORESCENT antibody technique, CHI-squared test, DESCRIPTIVE statistics, MEMBRANE proteins, DATA analysis software, ANTIGENS, PHENOTYPES, MICE, ABDOMINAL bloating
Abstract

Objective: Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti‐ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction. Methods: Serum from a patient with SSc with GI dysfunction but without defined SSc‐associated autoantibodies was used for autoantibody discovery. Immunoprecipitations performed with murine myenteric plexus lysates were on‐bead digested, and autoantigens were identified by mass spectrometry. Prevalence was determined, and clinical features associated with novel autoantibodies were evaluated in a SSc cohort using regression analyses. The expression of gephyrin in human GI tract tissue was examined by immunohistochemistry. Results: We identified gephyrin as a novel SSc autoantigen. Anti‐gephyrin antibodies were present in 9% of patients with SSc (16/188) and absent in healthy controls (0/46). Anti‐gephyrin antibody–positive patients had higher constipation scores (1.00 vs 0.50, P = 0.02) and were more likely to have severe constipation and severe distention/bloating (46% vs 15%, P = 0.005; 54% vs 25%, P = 0.023, respectively). Anti‐gephyrin antibody levels were significantly higher among patients with severe constipation (0.04 vs 0.00; P = 0.001) and severe distention and bloating (0.03 vs 0.004; P = 0.010). Severe constipation was associated with anti‐gephyrin antibodies even in the adjusted model. Importantly, gephyrin was expressed in the ENS, which regulates gut motility. Conclusion: Gephyrin is a novel ENS autoantigen that is expressed in human myenteric ganglia. Anti‐gephyrin autoantibodies are associated with the presence and severity of constipation in patients with SSc. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course.

Author

Kim, Ji Soo, Woods, Adrianne, Gutierrez‐Alamillo, Laura, Laffoon, Maureen, Wigley, Fredrick M., Hummers, Laura K., Rosen, Antony, Zeger, Scott, Domsic, Robyn T., Casciola‐Rosen, Livia, and Shah, Ami A.

Subjects
TUMOR risk factors, AUTOANTIBODIES, DISEASE progression, CONFIDENCE intervals, SYSTEMIC scleroderma, RANDOM forest algorithms, RISK assessment, ENZYME-linked immunosorbent assay, DESCRIPTIVE statistics, IMMUNITY, RESEARCH funding, LOGISTIC regression analysis, ODDS ratio
Abstract

Objectives: We examined whether an array of scleroderma autoantibodies associates with risk of cancer and could be useful tools for risk stratification. Methods: Scleroderma cancer cases and scleroderma controls without cancer from the Johns Hopkins Scleroderma Center and the University of Pittsburgh Scleroderma Center were studied. Sera were assayed by Lineblot and enzyme‐linked immunosorbent assay (ELISA) for autoantibodies against centromere, topoisomerase 1, RNA polymerase (POLR) 3, PM/Scl, Th/To, NOR90, U3 RNP, Ku, Ro52, U1RNP, and RNPC3. Logistic regression models were constructed to examine whether distinct autoantibodies associated with overall cancer at any time and cancer‐associated scleroderma (cancer occurring three years before and after scleroderma onset). The effects of having more than one autoantibody on cancer were further examined using random forest analysis. Results: A total of 676 cases and 687 controls were studied. After adjusting for relevant covariates, anti‐POLR3 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.03–2.11) and monospecific anti‐Ro52 (OR 2.19, 95% CI 1.29–3.74) were associated with an increased overall cancer risk, whereas anticentromere (OR 0.69, 95% CI 0.51–0.93) and anti‐U1RNP (OR 0.63, 95% CI 0.43–0.93) were associated with lower risk. When examining risk of cancer‐associated scleroderma, these immune responses remained associated with increased or decreased risk: anti‐POLR3 (OR 2.28, 95% CI 1.33–3.91), monospecific anti‐Ro52 (OR 2.58, 95% CI 1.05–6.30), anticentromere (OR 0.39, 95% CI 0.20–0.74), and anti‐U1RNP (OR 0.32, 95% CI 0.11–0.93). Anti‐Ro52 plus anti‐U1RNP or anti‐Th/To was associated with decreased cancer risk compared with anti‐Ro52 alone. Conclusions: These data suggest that five distinct scleroderma immune responses, alone or in combination, may be useful tools to stratify the risk of cancer for scleroderma patients. Further study examining cancer risk in autoantibody subgroups relative to the general population is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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27. List of Contributors

Author

Abraham, Roshini Sarah, primary, Albanesi, Cristina, additional, Alevizos, Ilias, additional, Anguita, Juan, additional, Antiochos, Brendan, additional, Aranow, Cynthia, additional, Atkinson, John P., additional, Austin, Howard A., additional, Babu, Subash, additional, Ballow, Mark C., additional, Balow, James E., additional, Belmont, John W., additional, Berek, Claudia, additional, Beukelman, Timothy, additional, Bhavsar, Tapan, additional, Bird, J. Andrew, additional, Blutt, Sarah E., additional, Boguniewicz, Mark, additional, Bonamichi-Santos, Rafael, additional, Boisson, Bertrand, additional, Borzova, Elena, additional, Boyaka, Prosper N., additional, Boyce, Joshua, additional, Browne, Sarah K., additional, Burks, Wesley, additional, Bustamante, Jacinta, additional, Calder, Virginia L., additional, Campbell, Matthew, additional, Cardones, Adela Rambi G., additional, Casanova, Jean-Laurent, additional, Castells, Mariana, additional, Cavacini, Lisa A., additional, Chan, Edwin S.L., additional, Chaplin, David D., additional, Chatham, W. Winn, additional, Chen, Edward S., additional, Chinen, Javier, additional, Christopher-Stine, Lisa, additional, Ciancanelli, Michael, additional, Cope, Andrew P., additional, Corry, David B., additional, Crea, Filippo, additional, Cron, Randy Q., additional, Cuellar-Rodriguez, Jennifer M., additional, Dalakas, Marinos C., additional, Dann, Sara M., additional, Diamond, Betty, additional, Du, Terry W., additional, Dupuis-Boisson, Stéphanie, additional, Eagar, Todd N., additional, Elmets, Craig A., additional, Erkan, Doruk, additional, Fanning, Laura, additional, Fikrig, Erol, additional, Flego, Davide, additional, Fleisher, Thomas A., additional, Fonacier, Luz, additional, Fontenot, Andrew P., additional, Freeman, Alexandra F., additional, Frew, Anthony J., additional, Fujihashi, Kohtaro, additional, Gadina, Massimo, additional, Gatt, Moshe E., additional, Gershwin, M. Eric, additional, Gillespie, Susan L., additional, Goronzy, Jörg J., additional, Goswami, Sangeeta, additional, Grattan, Clive E.H., additional, Greenspan, Neil S., additional, Gupta, Sarthak, additional, Gustafson, Claire E., additional, Hall, Russell P., additional, Hamilton, Robert G., additional, Harrington, Laurie E., additional, Harrison, Leonard C., additional, Hasni, Sarfaraz A., additional, Helbling, Arthur, additional, Hester, Joanna, additional, Holland, Steven M., additional, Hourcade, Dennis, additional, Huntington, Nicholas D., additional, Hwangpo, Tracy, additional, Imboden, John B., additional, Issa, Fadi, additional, Izraeli, Shai, additional, Jaffe, Elaine S., additional, Jalkanen, Sirpa, additional, Jones, Stacie, additional, Jouanguy, Emmanuelle, additional, Kabbani, Sarah, additional, Kaufmann, Stefan H.E., additional, Kheradmand, Farrah, additional, Kohn, Donald B., additional, Korngold, Robert, additional, Kovalszki, Anna, additional, Kuhns, Douglas B., additional, Kulkarni, Hrishikesh, additional, Kuo, Caroline Y., additional, Lahouti, Arash, additional, Landgren, C. Ola, additional, Laurence, Arian, additional, Lee, Joyce S., additional, Lemière, Catherine, additional, Leung, Donald Y.M., additional, Levinson, Arnold I., additional, Levy, Ofer, additional, Lewis, Dorothy E., additional, Lin, Phoebe, additional, Linkermann, Andreas, additional, Liuzzo, Giovanna, additional, Lockshin, Michael D., additional, Lord, Allison K., additional, Lozier, Jay N., additional, Luong, Amber, additional, Luqmani, Raashid, additional, Mackay, Meggan, additional, Maltzman, Jonathan S., additional, Mannon, Peter J., additional, Manns, Michael P., additional, Martin, James G., additional, Maynard, Craig L., additional, McCash, Samual, additional, McDonald, Douglas R., additional, Melby, Peter C., additional, Miller, Stephen D., additional, Mitchell, Anna L., additional, Mohd-Zaki, Amirah, additional, Mold, Carolyn, additional, Moller, David R., additional, Monos, Dimitrios S., additional, Mueller, Scott N., additional, Mulders-Manders, Catharina M., additional, Mulligan, Mark J., additional, Müller, Ulrich R., additional, Munshi, Pashna N., additional, Murata, Kazunori, additional, Murphy, Philip M., additional, Navasa, Nicolás, additional, Noel, Pierre, additional, Notarangelo, Luigi D., additional, Nussbaum, Robert L., additional, Nutman, Thomas B., additional, Nutt, Stephen L., additional, Oliveira, João B., additional, Ortel, Thomas L., additional, O'Shea, John J., additional, Pai, Sung-Yun, additional, Pandit, Lavannya, additional, Paul, Mary E., additional, Pearce, Simon H.S., additional, Pedicino, Daniela, additional, Peterson, Erik J., additional, Picard, Capucine, additional, Pittaluga, Stefania, additional, Priel, Debra Long, additional, Puck, Jennifer, additional, Puel, Anne, additional, Radbruch, Andreas, additional, Reece, Stephen T., additional, Reveille, John D., additional, Rich, Robert R., additional, Roifman, Chaim M., additional, Rosen, Antony, additional, Rosenbaum, James T., additional, Rosenzweig, Sergio D., additional, Rouse, Barry T., additional, Rowley, Scott D., additional, Sakaguchi, Shimon, additional, Salmi, Marko, additional, Sant, Andrea J., additional, Satola, Sarah W., additional, Saw, Valerie, additional, Schechter, Marcos C., additional, Schroeder, Harry W., additional, Segal, Benjamin M., additional, Selmi, Carlo, additional, Shankar, Sushma, additional, Sharma, Anu, additional, Sharma, Padmanee, additional, Shearer, William T., additional, Siegel, Richard M., additional, Simon, Anna, additional, Smith, Gideon P., additional, Stephens, David S., additional, Stephens, Robin, additional, Straumann, Alex, additional, Teos, Leyla Y., additional, Timares, Laura, additional, Tonnus, Wulf, additional, Torres, Raul M., additional, Uzel, Gülbü, additional, van der Hilst, Jeroen C.H., additional, van der Meer, Jos W.M., additional, Varga, John, additional, Vyas, Jatin M., additional, Waldman, Meryl, additional, Weiser, Peter, additional, Weller, Peter F., additional, Weyand, Cornelia M., additional, Wigley, Fredrick M., additional, Winchester, Robert J., additional, Wing, James B., additional, Wood, Kathryn J., additional, Wu, Xiaobo, additional, Xu, Hui, additional, Yee, Cassian, additional, and Zhang, Shen-Ying, additional

Published
2019
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29. Raynaud’s Phenomenon

Author

Wigley, Fredrick M., Herrick, Ariane L., Varga, John, editor, Denton, Christopher P., editor, and Wigley, Fredrick M., editor

Published
2012
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33. Myositis mimics in scleroderma: A case series of neuromuscular diseases that can co-exist in scleroderma

Author

Joyce, Emma, Wigley, Fredrick M, Hummers, Laura K, and Paik, Julie J

Abstract

We present a case series of four patients with systemic sclerosis and skeletal myopathy. While idiopathic inflammatory myopathies, or myositis, are thought to be the most common type of muscle disease seen in systemic sclerosis, we highlight four cases where unique clinical findings and careful assessment ruled out myositis mimics. Key diagnostic tools that can be helpful for clinicians to diagnose a neuromuscular disease are also detailed in this report.

Published
2024
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34. Cumulative disease damage and anti-PM/Scl antibodies are associated with a heavy burden of calcinosis in systemic sclerosis.

Author

Richardson, Carrie, Perin, Jamie, Zeger, Scott, Wigley, Fredrick M, Hummers, Laura K, Casciola-Rosen, Livia, Rosen, Antony, and Shah, Ami A

Subjects
HIP joint physiology, AUTOANTIBODIES, DISEASE progression, STRUCTURAL equation modeling, THREE-dimensional imaging, CONFIDENCE intervals, PULMONARY hypertension, CLASSIFICATION, SYSTEMIC scleroderma, ACQUISITION of data, PATIENTS, INTERSTITIAL lung diseases, RISK assessment, COMPARATIVE studies, CALCINOSIS, MEDICAL records, DESCRIPTIVE statistics, RESEARCH funding, LOGISTIC regression analysis, COMPUTED tomography, ODDS ratio, LONGITUDINAL method, DISEASE complications
Abstract

Objectives Ectopic calcification (calcinosis) is a common complication of SSc, but a subset of SSc patients has a heavy burden of calcinosis. We examined whether there are unique risk factors for a heavy burden of calcinosis, as compared with a light burden or no calcinosis. Methods We reviewed the medical records of all patients in the Johns Hopkins Scleroderma Center Research Registry with calcinosis to quantify calcinosis burden using pre-specified definitions. We performed latent class analysis to identify SSc phenotypic classes. We used multinomial logistic regression to determine whether latent phenotypic classes and autoantibodies were independent risk factors for calcinosis burden. Results Of all patients, 29.4% (997/3388) had calcinosis, and 13.5% (130/963) of those with calcinosis had a heavy burden. The latent phenotypic class with predominantly diffuse skin disease and higher disease severity (characterized by pulmonary hypertension, interstitial lung disease, cardiomyopathy, severe RP, gastrointestinal involvement, renal crisis, myopathy and/or tendon friction rubs) was associated with an increased risk of both a heavy burden [odds ratio (OR) 6.92, 95% CI 3.66, 13.08; P  < 0.001] and a light burden (OR 2.88, 95% CI 2.11, 3.95; P  < 0.001) of calcinosis compared with the phenotypic class with predominantly limited skin disease. Autoantibodies to PM/Scl were strongly associated with a heavy burden of calcinosis (OR 17.31, 95% CI 7.72, 38.81; P  < 0.001) and to a lesser degree a light burden of calcinosis (OR 3.59, 95% CI 1.84, 7.00; P  < 0.001). Conclusions Calcinosis burden is associated with cumulative SSc-related tissue damage. Independent of disease severity, autoantibodies to PM/Scl are also associated with a heavy burden of calcinosis. [ABSTRACT FROM AUTHOR]

Published
2023
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42. Contributors

Author

Abramson, Steven, primary, An, KaiNan, additional, Andrade, Felipe, additional, Ardoin, Stacy P., additional, Barton, Anne, additional, Baughman, Robert P., additional, Beaton, Dorcas E., additional, Beere, Helen M., additional, Beltran, Javier, additional, Bending, David, additional, Bennett, Robert M., additional, Bermas, Bonnie L., additional, Bertsias, George, additional, Bhardwaj, Nina, additional, Bijlsma, Johannes W.J., additional, Bockenstedt, Linda K., additional, Boers, Maarten, additional, Boilard, Eric, additional, Boin, Francesco, additional, Boumpas, Dimitrios T., additional, Boyle, David L., additional, Bradley, Sean, additional, Brown, Matthew, additional, Buch, Maya, additional, Buckley, Christopher D., additional, Budd, Ralph C., additional, Burg, Nathalie, additional, Burns, Christopher M., additional, Cannella, Amy C., additional, Carter, John D., additional, Chakravarty, Eliza F., additional, Chakravarty, Soumya D., additional, Chang, Christopher, additional, Cheng, Joseph S., additional, Chiodo, Christopher P., additional, Chung, Sharon, additional, Cleland, Leslie G., additional, Cohen, Stanley, additional, Colbert, Robert A., additional, Cook, Paul P., additional, Craft, Joseph E., additional, Crofford, Leslie J., additional, Cronstein, Bruce N., additional, Crow, Mary K., additional, Crowson, Cynthia S., additional, Culley, Kirsty L., additional, Cunnane, Gaye, additional, Dall'Era, Maria, additional, Darrah, Erika, additional, Davis, John M., additional, Bari, Cosimo De, additional, Dell'Accio, Francesco, additional, Diamond, Betty, additional, Di Cesare, Paul E., additional, Dixit, Rajiv, additional, Drenth, Joost P.H., additional, Dustin, Michael L., additional, El-Gabalawy, Hani S., additional, Elmamoun, Musaab, additional, Erickson, Alan R., additional, Erkan, Doruk, additional, Eyre, Stephen, additional, Fanouriakis, Antonis, additional, Felson, David T., additional, Field, Max, additional, Filer, Andrew, additional, Firestein, Gary S., additional, Fishman, Felicity G., additional, FitzGerald, Oliver, additional, Flaherty, John P., additional, Fors, César E., additional, Fortner, Karen A., additional, Gabriel, Sherine E., additional, Gasque, Philippe, additional, Gershwin, M. Eric, additional, Gladue, Heather S., additional, Goldring, Mary B., additional, Goldring, Steven R., additional, Golightly, Yvonne M., additional, Goodman, Stuart, additional, Gordon, Siamon, additional, Grassi, Walter, additional, Green, Douglas R., additional, Greenspan, Adam, additional, Gregersen, Peter, additional, Grimaldi, Christine, additional, Guilherme, Luiza, additional, Hajj-Ali, Rula A., additional, Haudenschild, Dominik R., additional, Hellmann, David B., additional, Holmdahl, Rikard, additional, Hsu, Joyce J., additional, Huddleston, James I., additional, Hudson, Alan P., additional, Huizinga, Thomas W.J., additional, Hunder, Gene G., additional, Iversen, Maura D., additional, Jacobs, Johannes W.G., additional, Jen, Ho, additional, Jordan, Joanne M., additional, Jorizzo, Joseph L., additional, Kalil, Jorge, additional, Kaufman, Kenton, additional, Kaufman, William S., additional, Kavanaugh, Arthur, additional, Keenan, Robert T., additional, Kenna, Tony, additional, Kerr, Darcy A., additional, Koch, Alisa E., additional, Kono, Dwight H., additional, Korsten, Peter, additional, Krakow, Deborah, additional, Krasnokutsky, Svetlana, additional, Lafeber, Floris P.J.G., additional, Lambert, Robert G.W., additional, Lane, Nancy E., additional, Langford, Carol A., additional, Laskin, Daniel M., additional, Layh-Schmitt, Gerlinde, additional, Lee, Lela A., additional, Lee, Tzielan C., additional, Lockshin, Michael D., additional, Lozada, Carlos J., additional, Lundberg, Ingrid E., additional, Luqmani, Raashid, additional, Luyten, Frank P., additional, Mader, Reuven, additional, Maksymowych, Walter, additional, Markenson, Joseph A., additional, Martin, Scott David, additional, Matteson, Eric L., additional, McGregor, Laura, additional, McInnes, Iain B., additional, McNamara, Elizabeth K., additional, Mikuls, Ted R., additional, Miller, Mark S., additional, Ming, Pedro Azevedo, additional, Moder, Kevin G., additional, Monach, Paul A., additional, Moulton, Vaishali R., additional, Nagaraju, Kanneboyina, additional, Nelson, Amanda E., additional, Nigrovic, Peter A., additional, Nistala, Kiran, additional, O'Dell, James R., additional, Okada, Yasunori, additional, Østergaard, Mikkel, additional, Otero, Miguel, additional, Palmer, Bradley M., additional, Panush, Richard S., additional, Peng, Stanford L., additional, Pillai, Shiv, additional, Pillinger, Michael H., additional, Plüddemann, Annette, additional, Polston, Gregory R., additional, Porcelli, Steven A., additional, Price, Mark D., additional, Reed, Ann M., additional, Reveille, John D., additional, Robinson, Angela B., additional, Robinson, Philip, additional, Robinson, William H., additional, Roosendaal, Goris, additional, Rosen, Antony, additional, Rosenbaum, James T., additional, Rosenberg, Andrew E., additional, Ruderman, Eric M., additional, Saag, Kenneth G., additional, Salmon, Jane E., additional, Sammaritano, Lisa R., additional, Samuels, Jonathan, additional, Sandborg, Christy I., additional, Sawalha, Amr H., additional, Saxena, Amit, additional, Schett, Georg, additional, Schutgens, Roger E.G., additional, Seldin, David C., additional, Shah, Binita, additional, Sikora, Keith A., additional, Simon, Anna, additional, Siraj, Dawd S., additional, Sorkin, Linda S., additional, St. Clair, E. William, additional, Stamp, Lisa K., additional, Stone, John H., additional, Suarez-Fueyo, Abel, additional, Svensson, Camilla I., additional, Sweiss, Nadera J., additional, Swigart, Carrie R., additional, Szekanecz, Zoltán, additional, Tait, Stephen, additional, Tanne, Antoine, additional, Taylor, Peter C., additional, Terkeltaub, Robert, additional, Theofilopoulos, Argyrios N., additional, Thornhill, Thomas S., additional, Torok, Kathryn S., additional, Toth, Michael J., additional, Tozman, Elaine C., additional, Trouw, Leendert A., additional, Tsokos, George C., additional, Tugwell, Peter, additional, Tutuncu, Zuhre, additional, Upadhyaya, Shivam, additional, Van, Annette H.M., additional, van der Linden, Sjef, additional, Van, Jos W.M., additional, Van, Jacob M., additional, Meter, Heather Van, additional, van Vollenhoven, Ronald F., additional, van Vulpen, Lize F.D., additional, Varga, John, additional, Vaseer, Samera, additional, Vasquez-Castellanos, Raul, additional, Veale, Douglas J., additional, Wakefield, Richard J., additional, Wallace, Mark S., additional, Wang, Ruoning, additional, Wang, Tingting, additional, Warshaw, David M., additional, Wedderburn, Lucy R., additional, Werth, Victoria P., additional, Wigley, Fredrick M., additional, Wofsy, David, additional, Wollheim, Frank A., additional, Wondimu, Elisabeth, additional, Wong, Cyrus, additional, Wortmann, Robert L., additional, Yelin, Edward, additional, Zayat, Ahmed, additional, Zou, Yong-Rui, additional, and Zurier, Robert B., additional

Published
2017
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47. Reply

Author

Shah, Ami A., Rosen, Antony, Hummers, Laura K., Wigley, Fredrick M., Xu, George, Elledge, Stephen J., and Casciola‐Rosen, Livia

Published
2017
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48. Digital ulcers in SSc treated with oral treprostinil: a randomized, double-blind, placebo-controlled study with open-label follow-up

Author

Seibold, James R., Wigley, Fredrick M., Schiopu, Elena, Denton, Christopher P., Silver, Richard M., Steen, Virginia D., Domsic, Robyn, Medsger, Thomas A., Jr, Mayes, Maureen D., Chatterjee, Soumya, Chung, Lorinda, Csuka, Mary Ellen, Khanna, Dinesh, Collier, David, Frech, Tracy M., Molitor, Jerry A., Rothfield, Naomi, Herrick, Ariane L., Simms, Robert, Pope, Janet E., Baron, Murray, Hsu, Vivien M., Peng, Stanford L., Spiera, Robert, Fessler, Barri J., Kahaleh, Bashar, Varga, John, Laliberte, Kevin, Wade, Michael, and Rollins, Kristan

Published
2017
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