Associations between rheumatoid arthritis clinical factors with synovial cell types and states

Accelerating Medicines Partnership Program: RA/SLE Network; Dana Weisenfeld; Fan Zhang; Laura Donlin; Anna helena Jonsson; William Apruzzese; Debbie Campbell; Deepak a. Rao; Kevin Wei; V. michael Holers; Ellen Gravallese; Larry Moreland; Susan Goodman; Michael Brenner; Soumya Raychaudhuri; Andrew Filer; Jennifer Anolik; Vivian Bykerk; Katherine p. Liao

doi:10.1002/art.42726

Associations between rheumatoid arthritis clinical factors with synovial cell types and states

Accelerating Medicines Partnership Program: RA/SLE Network, Dana Weisenfeld, Fan Zhang, Laura Donlin, Anna helena Jonsson, William Apruzzese, Debbie Campbell, Deepak a. Rao, Kevin Wei, V. michael Holers, Ellen Gravallese, Larry Moreland, Susan Goodman, Michael Brenner, Soumya Raychaudhuri, Andrew Filer, Jennifer Anolik, Vivian Bykerk, Katherine p. Liao^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.

METHODS: The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.

RESULTS: We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p < 0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p < 0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.

CONCLUSION: In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

Original language	English
Journal	Arthritis & Rheumatology (Hoboken)
Early online date	4 Oct 2023
DOIs	https://doi.org/10.1002/art.42726
Publication status	E-pub ahead of print - 4 Oct 2023

Bibliographical note

Funding Information:
Supported by the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Program (see Appendix A). AMP is a public‐private partnership (AbbVie Inc., Arthritis Foundation, Bristol‐Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, LLC, Lupus Foundation of America, Lupus Research Alliance, Merck & Co., Inc., NIH/National Institute of Allergy and Infectious Diseases, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer Inc., Rheumatology Research Foundation, and Sanofi and Takeda Pharmaceuticals International, Inc.) created to develop new ways of identifying and validating promising biologic targets for diagnostics and drug development. Supported by NIH (grants UH2‐AR‐067676, UH2‐AR‐067677, UH2‐AR‐067679, UH2‐AR‐067681, UH2‐AR‐067685, UH2‐AR‐067688, UH2‐AR‐067689, UH2‐ AR‐067690, UH2‐AR‐067691, UH2‐AR‐067694, and UM2‐AR‐067678). Accelerating Medicines Partnership and AMP are registered service marks of the US Department of Health and Human Services. Supported by NIH P30‐AR‐072577 (to Ms. Weisenfeld and Dr. Liao); PhRMA (to Dr. Zhang); NIH NIAID R01‐AI‐148435 (to Dr. Donlin); Rheumatology Research Foundation Investigator Award and Arthritis National Research Foundation award (Dr. Jonsson); NIH NIAMS K08‐AR‐072791 and Burroughs Wellcome Fund Career Award in Medical Sciences (to Ms. Rao); NIH NIAMS K08‐AR‐077037, Rheumatology Research Foundation Innovative Research Award, and Burroughs Wellcome Fund Career Award in Medical Sciences (to Dr. Wei); NIH NIAMS R01‐AR‐073833 and R01‐AR‐073290 (to Dr. Brenner); NIH NHGRI U01‐HG‐009379 and NIAMS R01‐AR‐063759 (to Dr. Raychaudhuri); Research into Inflammatory Arthritis Centre Versus Arthritis (22072), IMI‐RTCure (777357), and the NIHR Birmingham Biomedical Research Centre (BRC‐1215‐20009) (to Dr. Filer); and NIH NIAMS R21‐AR‐071670 and P30‐AR‐069655 (to Dr. Anolik).

Publisher Copyright:
© 2023 American College of Rheumatology.

ASJC Scopus subject areas

Immunology and Allergy
Rheumatology
Immunology

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10.1002/art.42726

Cite this

Accelerating Medicines Partnership Program: RA/SLE Network, Weisenfeld, D., Zhang, F., Donlin, L., Jonsson, A. H., Apruzzese, W., Campbell, D., Rao, D. A., Wei, K., Holers, V. M., Gravallese, E., Moreland, L., Goodman, S., Brenner, M., Raychaudhuri, S., Filer, A., Anolik, J., Bykerk, V., & Liao, K. P. (2023). Associations between rheumatoid arthritis clinical factors with synovial cell types and states. Arthritis & Rheumatology (Hoboken). Advance online publication. https://doi.org/10.1002/art.42726

@article{de2d088235c54287bf247df2fb37d67e,

title = "Associations between rheumatoid arthritis clinical factors with synovial cell types and states",

abstract = "OBJECTIVE: Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.METHODS: The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.RESULTS: We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p < 0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p < 0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.CONCLUSION: In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.",

author = "{Accelerating Medicines Partnership Program: RA/SLE Network} and Dana Weisenfeld and Fan Zhang and Laura Donlin and Jonsson, {Anna helena} and William Apruzzese and Debbie Campbell and Rao, {Deepak a.} and Kevin Wei and Holers, {V. michael} and Ellen Gravallese and Larry Moreland and Susan Goodman and Michael Brenner and Soumya Raychaudhuri and Andrew Filer and Jennifer Anolik and Vivian Bykerk and Liao, {Katherine p.} and Saba Nayar and Karim Raza and Ilfita Sahbudin and Dagmar Scheel-Toellner",

note = "Funding Information: Supported by the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Program (see Appendix A). AMP is a public‐private partnership (AbbVie Inc., Arthritis Foundation, Bristol‐Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, LLC, Lupus Foundation of America, Lupus Research Alliance, Merck & Co., Inc., NIH/National Institute of Allergy and Infectious Diseases, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer Inc., Rheumatology Research Foundation, and Sanofi and Takeda Pharmaceuticals International, Inc.) created to develop new ways of identifying and validating promising biologic targets for diagnostics and drug development. Supported by NIH (grants UH2‐AR‐067676, UH2‐AR‐067677, UH2‐AR‐067679, UH2‐AR‐067681, UH2‐AR‐067685, UH2‐AR‐067688, UH2‐AR‐067689, UH2‐ AR‐067690, UH2‐AR‐067691, UH2‐AR‐067694, and UM2‐AR‐067678). Accelerating Medicines Partnership and AMP are registered service marks of the US Department of Health and Human Services. Supported by NIH P30‐AR‐072577 (to Ms. Weisenfeld and Dr. Liao); PhRMA (to Dr. Zhang); NIH NIAID R01‐AI‐148435 (to Dr. Donlin); Rheumatology Research Foundation Investigator Award and Arthritis National Research Foundation award (Dr. Jonsson); NIH NIAMS K08‐AR‐072791 and Burroughs Wellcome Fund Career Award in Medical Sciences (to Ms. Rao); NIH NIAMS K08‐AR‐077037, Rheumatology Research Foundation Innovative Research Award, and Burroughs Wellcome Fund Career Award in Medical Sciences (to Dr. Wei); NIH NIAMS R01‐AR‐073833 and R01‐AR‐073290 (to Dr. Brenner); NIH NHGRI U01‐HG‐009379 and NIAMS R01‐AR‐063759 (to Dr. Raychaudhuri); Research into Inflammatory Arthritis Centre Versus Arthritis (22072), IMI‐RTCure (777357), and the NIHR Birmingham Biomedical Research Centre (BRC‐1215‐20009) (to Dr. Filer); and NIH NIAMS R21‐AR‐071670 and P30‐AR‐069655 (to Dr. Anolik). Publisher Copyright: {\textcopyright} 2023 American College of Rheumatology.",

year = "2023",

month = oct,

day = "4",

doi = "10.1002/art.42726",

language = "English",

journal = "Arthritis & Rheumatology (Hoboken)",

issn = "2326-5191",

publisher = "Wiley",

}

Accelerating Medicines Partnership Program: RA/SLE Network, Weisenfeld, D, Zhang, F, Donlin, L, Jonsson, AH, Apruzzese, W, Campbell, D, Rao, DA, Wei, K, Holers, VM, Gravallese, E, Moreland, L, Goodman, S, Brenner, M, Raychaudhuri, S, Filer, A, Anolik, J, Bykerk, V & Liao, KP 2023, 'Associations between rheumatoid arthritis clinical factors with synovial cell types and states', Arthritis & Rheumatology (Hoboken). https://doi.org/10.1002/art.42726

TY - JOUR

T1 - Associations between rheumatoid arthritis clinical factors with synovial cell types and states

AU - Accelerating Medicines Partnership Program: RA/SLE Network

AU - Weisenfeld, Dana

AU - Zhang, Fan

AU - Donlin, Laura

AU - Jonsson, Anna helena

AU - Apruzzese, William

AU - Campbell, Debbie

AU - Rao, Deepak a.

AU - Wei, Kevin

AU - Holers, V. michael

AU - Gravallese, Ellen

AU - Moreland, Larry

AU - Goodman, Susan

AU - Brenner, Michael

AU - Raychaudhuri, Soumya

AU - Filer, Andrew

AU - Anolik, Jennifer

AU - Bykerk, Vivian

AU - Liao, Katherine p.

AU - Nayar, Saba

AU - Raza, Karim

AU - Sahbudin, Ilfita

AU - Scheel-Toellner, Dagmar

N1 - Funding Information: Supported by the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Program (see Appendix A). AMP is a public‐private partnership (AbbVie Inc., Arthritis Foundation, Bristol‐Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, LLC, Lupus Foundation of America, Lupus Research Alliance, Merck & Co., Inc., NIH/National Institute of Allergy and Infectious Diseases, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer Inc., Rheumatology Research Foundation, and Sanofi and Takeda Pharmaceuticals International, Inc.) created to develop new ways of identifying and validating promising biologic targets for diagnostics and drug development. Supported by NIH (grants UH2‐AR‐067676, UH2‐AR‐067677, UH2‐AR‐067679, UH2‐AR‐067681, UH2‐AR‐067685, UH2‐AR‐067688, UH2‐AR‐067689, UH2‐ AR‐067690, UH2‐AR‐067691, UH2‐AR‐067694, and UM2‐AR‐067678). Accelerating Medicines Partnership and AMP are registered service marks of the US Department of Health and Human Services. Supported by NIH P30‐AR‐072577 (to Ms. Weisenfeld and Dr. Liao); PhRMA (to Dr. Zhang); NIH NIAID R01‐AI‐148435 (to Dr. Donlin); Rheumatology Research Foundation Investigator Award and Arthritis National Research Foundation award (Dr. Jonsson); NIH NIAMS K08‐AR‐072791 and Burroughs Wellcome Fund Career Award in Medical Sciences (to Ms. Rao); NIH NIAMS K08‐AR‐077037, Rheumatology Research Foundation Innovative Research Award, and Burroughs Wellcome Fund Career Award in Medical Sciences (to Dr. Wei); NIH NIAMS R01‐AR‐073833 and R01‐AR‐073290 (to Dr. Brenner); NIH NHGRI U01‐HG‐009379 and NIAMS R01‐AR‐063759 (to Dr. Raychaudhuri); Research into Inflammatory Arthritis Centre Versus Arthritis (22072), IMI‐RTCure (777357), and the NIHR Birmingham Biomedical Research Centre (BRC‐1215‐20009) (to Dr. Filer); and NIH NIAMS R21‐AR‐071670 and P30‐AR‐069655 (to Dr. Anolik). Publisher Copyright: © 2023 American College of Rheumatology.

PY - 2023/10/4

Y1 - 2023/10/4

N2 - OBJECTIVE: Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.METHODS: The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.RESULTS: We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p < 0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p < 0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.CONCLUSION: In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

AB - OBJECTIVE: Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.METHODS: The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.RESULTS: We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p < 0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p < 0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.CONCLUSION: In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

UR - http://www.scopus.com/inward/record.url?scp=85179700063&partnerID=8YFLogxK

U2 - 10.1002/art.42726

DO - 10.1002/art.42726

M3 - Article

C2 - 37791989

SN - 2326-5191

JO - Arthritis & Rheumatology (Hoboken)

JF - Arthritis & Rheumatology (Hoboken)

ER -

Associations between rheumatoid arthritis clinical factors with synovial cell types and states

Abstract

Bibliographical note

ASJC Scopus subject areas

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