UW Rheumatology Biorepository

A biorepository, or a biobank, is a secure and confidential way to store information and biological material (like blood or tissue samples) for research. Volunteers provide information about their health and their demographics (for example, medications and age) and donate blood or other tissues to be stored in highly secure biorepositories. Sometimes relevant information from the electronic medical record is included. Researchers study the information and biological materials to advance our understanding of disease as well as to develop improved clinical tests and treatments to improve human health and reduce human suffering.

History

The University of Wisconsin Rheumatology Biorepository was first established in 2015 by Dr. Miriam Shelef. The first people invited to participate in the biorepository were people with rheumatoid arthritis and people without any rheumatologic, autoimmune, or inflammatory conditions. (Samples and information from this latter group of people are extremely helpful for researchers to use as a comparison group, or control group, to identify what might be different in whichever condition is being studied.) Over 500 people with rheumatoid arthritis and over 100 people without rheumatologic, autoimmune, or inflammatory conditions chose to provide information and blood. 

In collaboration with Dr. Shivani Garg, the biorepository later expanded to include information and blood from people with systemic lupus erythematosus. Dr. Sara McCoy further expanded the biorepository to include people with Sjögren’s disease. 

The biorepository also grew to better understand COVID-19. In the spring of 2020, over 100 people who had recently had COVID-19 agreed to provide clinical information and blood samples multiple times after their COVID-19 illness. Also, people who received COVID-19 vaccinations prior to a COVID-19 illness and people who were hospitalized with COVID-19 volunteered to participate. Ultimately, many of these participants have updated their clinical information and provided additional blood samples for four years after their initial COVID-19 illness or vaccination. 

Results

The UW Rheumatology Biorepository has enabled many important discoveries, as described in the publications below. 

For example, new autoantibodies have been discovered in rheumatoid arthritis and Sjögren’s disease that are being further evaluated as improved diagnostic tests. Also, important discoveries were made about both the healthy protective immune response and autoimmune responses after COVID-19. Researchers continue to study rheumatoid arthritis, lupus, Sjögren’s disease, and COVID-19, including long COVID. 

Contributors

The UW Rheumatology Biorepository would not be possible without the contributions of many people such as:

• The altruistic volunteers who contribute biological samples and information
• The caring and dedicated researchers who established, maintain, and protect the biorepository
• The physicians and staff at UW Health who assist with volunteer recruitment and blood draws
• The UW Institutional Review Board which regulates and monitors the biorepository to protect research participants
• The institutions and generous donors that provide financial support, such as the Wisconsin Partnership Program, the Doris Duke Charitable Foundation, the Congressionally Directed Medical Research Program, the National Institutes of Health (NIH), and the University of Wisconsin Department of Medicine. If you would like to make a gift to support the biorepository, please visit the UW Foundation or contact us at 608-709-9388 or pete.schmeling@supportuw.org.

Rebernick R, Fahmy L, Glover C, Bawadekar M, Shim D, Holmes CL, Rademacher N, Potluri H, Bartels CM, Shelef MA. DNA Area and NETosis Analysis (DANA): a High-Throughput Method to Quantify Neutrophil Extracellular Traps in Fluorescent Microscope Images. Biol Proced Online. 2018 Apr 1;20:7. doi: 10.1186/s12575-018-0072-y. PMID: 29618953; PMCID: PMC5878938.

Holmes CL, Peyton CG, Bier AM, Donlon TZ, Osman F, Bartels CM, Shelef MA. Reduced IgG titers against pertussis in rheumatoid arthritis: Evidence for a citrulline-biased immune response and medication effects. PLoS One. 2019 May 28;14(5):e0217221. doi: 10.1371/journal.pone.0217221. PMID: 31136605; PMCID: PMC6538243.

Mergaert AM, Bawadekar M, Nguyen TQ, Massarenti L, Holmes CL, Rebernick R, Schrodi SJ, Shelef MA. Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with a Single Nucleotide Polymorphism in PADI4 in North Americans. Int J Mol Sci. 2019 Jun 25;20(12):3093. doi: 10.3390/ijms20123093. PMID: 31242568; PMCID: PMC6627847.

Zheng Z, Mergaert AM, Fahmy LM, Bawadekar M, Holmes CL, Ong IM, Bridges AJ, Newton MA, Shelef MA. Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Feb;72(2):262-272. doi: 10.1002/art.41074. Epub 2019 Dec 10. PMID: 31397047; PMCID: PMC6994383.

Zheng Z, Mergaert AM, Ong IM, Shelef MA, Newton MA. MixTwice: large-scale hypothesis testing for peptide arrays by variance mixing. Bioinformatics. 2021 Sep 9;37(17):2637-2643. doi: 10.1093/bioinformatics/btab162. PMID: 33693483; PMCID: PMC8428605.

Heffron AS, McIlwain SJ, Amjadi MF, Baker DA, Khullar S, Armbrust T, Halfmann PJ, Kawaoka Y, Sethi AK, Palmenberg AC, Shelef MA, O'Connor DH, Ong IM. The landscape of antibody binding in SARS-CoV-2 infection. PLoS Biol. 2021 Jun 18;19(6):e3001265. doi: 10.1371/journal.pbio.3001265. PMID: 34143766; PMCID: PMC8245122.

Amjadi MF, O'Connell SE, Armbrust T, Mergaert AM, Narpala SR, Halfmann PJ, Bashar SJ, Glover CR, Heffron AS, Taylor A, Flach B, O'Connor DH, Kawaoka Y, McDermott AB, Sethi AK, Shelef MA. Specific COVID-19 Symptoms Correlate with High Antibody Levels against SARS-CoV-2. Immunohorizons. 2021 Jun 17;5(6):466-476. doi: 10.4049/immunohorizons.2100022. PMID: 34398806; PMCID: PMC8452279.

Massarenti L, Enevold C, Damgaard D, Ødum N, Garred P, Frisch M, Shelef MA, Jacobsen S, Nielsen CH. PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking. Front Immunol. 2021 Oct 18;12:707690. doi: 10.3389/fimmu.2021.707690. PMID: 34733271; PMCID: PMC8558474.

Mergaert AM, Zheng Z, Denny MF, Amjadi MF, Bashar SJ, Newton MA, Malmström V, Grönwall C, McCoy SS, Shelef MA. Rheumatoid Factor and Anti-Modified Protein Antibody Reactivities Converge on IgG Epitopes. Arthritis Rheumatol. 2022 Jun;74(6):984-991. doi: 10.1002/art.42064. Epub 2022 Apr 10. PMID: 35001558; PMCID: PMC9156533.

Adi W, Biswas D, Shelef MA, Yesilkoy F. Multiplexed COVID-19 antibody quantification from human sera using label-free nanoplasmonic biosensors. Biomed Opt Express. 2022 Mar 16;13(4):2130-2143. doi: 10.1364/BOE.454919. PMID: 35519285; PMCID: PMC9045896.

Amjadi MF, Adyniec RR, Gupta S, Bashar SJ, Mergaert AM, Braun KM, Moreno GK, O'Connor DH, Friedrich TC, Safdar N, McCoy SS, Shelef MA. Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination. J Infect Dis. 2022 Nov 28;226(11):1897-1902. doi: 10.1093/infdis/jiac263. PMID: 35758987; PMCID: PMC9278254.

Beisenova A, Adi W, Bashar SJ, Velmurugan M, Germanson KB, Shelef MA, Yesilkoy F. Machine-learning-aided multiplexed nanobiosensor for COVID-19 population immunity profiling. Sensors & Diagnostics. 2023 Jul 06; 2, 1186-1198. (preprint: medRxiv. 2023 Feb: 2023.02.06.23285535).

Amjadi MF, Parker MH, Adyniec RR, Zheng Z, Robbins AM, Bashar SJ, Denny MF, McCoy SS, Ong IM, Shelef MA. Novel and unique rheumatoid factors cross-react with viral epitopes in COVID-19. J Autoimmun. 2024 Jan;142:103132. doi: 10.1016/j.jaut.2023.103132. Epub 2023 Nov 11. PMID: 37956528; PMCID: PMC10957334

Parker M, Zheng Z, Lasarev MR, Larsen MC, Vande Loo A, Alexandridis RA, Newton MA, Shelef MA, McCoy SS. Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology. Ann Rheum Dis. 2024 Aug 27;83(9):1169-1180. doi: 10.1136/ard-2023-224936. PMID: 38702176; PMCID: PMC11569393.

Bashar SJ, Zheng Z, Mergaert AM, Adyniec RR, Gupta S, Amjadi MF, McCoy SS, Newton MA, Shelef MA. Limited Biomarker Potential for IgG Autoantibodies Reactive to Linear Epitopes in Systemic Lupus Erythematosus or Spondyloarthropathy. Antibodies (Basel). 2024 Oct 12;13(4):87. doi: 10.3390/antib13040087. PMID: 39449329; PMCID: PMC11503330.

Titi AH, Krisko BT, Bashar SJ, Adyniec RR, Parker MH, Murren NF, Myhr CB, Shelef MA. Rheumatoid Arthritis-Associated Rheumatoid Factors Post-COVID-19. Frontiers in Immunology. 2025 Feb 13:16:1553540. doi: 10.3389/fimmu.2025.1553540. PMID: PMC11864925; PMCID: PMC11864925.