Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis
Objective The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cel...
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2025-01-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11742 |
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| author | Julia M. Scheffler Christina Drevinge Catharina Lindholm Inger Gjertsson Kristina Lend Merete Lund Hetland Mikkel Østergaard Till Uhlig Marte Schrumpf Heiberg Espen A. Haavardsholm Michael T. Nurmohamed Jon Lampa Tuulikki Sokka‐Isler Dan Nordström Kim Hørslev‐Petersen Bjorn Gudbjornsson Gerdur Gröndal Ronald vanVollenhoven Hans Carlsten Mattias Lorentzon Anna‐Karin Hultgård Ekwall Anna Rudin Ulrika Islander |
| author_facet | Julia M. Scheffler Christina Drevinge Catharina Lindholm Inger Gjertsson Kristina Lend Merete Lund Hetland Mikkel Østergaard Till Uhlig Marte Schrumpf Heiberg Espen A. Haavardsholm Michael T. Nurmohamed Jon Lampa Tuulikki Sokka‐Isler Dan Nordström Kim Hørslev‐Petersen Bjorn Gudbjornsson Gerdur Gröndal Ronald vanVollenhoven Hans Carlsten Mattias Lorentzon Anna‐Karin Hultgård Ekwall Anna Rudin Ulrika Islander |
| author_sort | Julia M. Scheffler |
| collection | DOAJ |
| description | Objective The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease‐modifying antirheumatic drugs (bDMARDs) in RA. Methods Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C‐reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Results HR‐pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = −0.38, P = 0.04) and CXCR3+Th17 cells (r = −0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. Conclusion MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA. |
| format | Article |
| id | doaj-art-c5d5435998d845f093cca7b70e08581a |
| institution | Kabale University |
| issn | 2578-5745 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj-art-c5d5435998d845f093cca7b70e08581a2025-02-04T06:21:23ZengWileyACR Open Rheumatology2578-57452025-01-0171n/an/a10.1002/acr2.11742Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid ArthritisJulia M. Scheffler0Christina Drevinge1Catharina Lindholm2Inger Gjertsson3Kristina Lend4Merete Lund Hetland5Mikkel Østergaard6Till Uhlig7Marte Schrumpf Heiberg8Espen A. Haavardsholm9Michael T. Nurmohamed10Jon Lampa11Tuulikki Sokka‐Isler12Dan Nordström13Kim Hørslev‐Petersen14Bjorn Gudbjornsson15Gerdur Gröndal16Ronald vanVollenhoven17Hans Carlsten18Mattias Lorentzon19Anna‐Karin Hultgård Ekwall20Anna Rudin21Ulrika Islander22University of Gothenburg Gothenburg SwedenUniversity of Gothenburg Gothenburg SwedenUniversity of Gothenburg and Sahlgrenska University Hospital Gothenburg SwedenUniversity of Gothenburg and Sahlgrenska University Hospital Gothenburg SwedenKarolinska Institute, Karolinska University Hospital, Stockholm, Sweden, and Amsterdam University Medical Center Amsterdam the NetherlandsRigshospitalet, Glostrup, Denmark, and University of Copenhagen Copenhagen DenmarkRigshospitalet, Glostrup, Denmark, and University of Copenhagen Copenhagen DenmarkDiakonhjemmet Hospital Oslo NorwayDiakonhjemmet Hospital Oslo NorwayDiakonhjemmet Hospital and University of Oslo Oslo NorwayAmsterdam Rheumatology and Immunology Center, Reade, the Netherlands, and Amsterdam University Medical Center Amsterdam the NetherlandsKarolinska Institute, Karolinska University Hospital Stockholm SwedenUniversity of Eastern Finland, Jyväskylä Central Hospital Jyväskylä FinlandHelsinki University and University Hospital Helsinki FinlandDanish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark, and University of Southern Denmark Odense DenmarkLandspitali National University Hospital of Iceland and University of Iceland Reykjavik IcelandLandspitali National University Hospital of Iceland and University of Iceland Reykjavik IcelandKarolinska Institute, Karolinska University Hospital, Stockholm, Sweden, and Amsterdam University Medical Center Amsterdam the NetherlandsUniversity of Gothenburg and Sahlgrenska University Hospital Gothenburg SwedenUniversity of Gothenburg, Gothenburg, Sweden and Australian Catholic University Melbourne AustraliaUniversity of Gothenburg and Sahlgrenska University Hospital Gothenburg SwedenUniversity of Gothenburg and Sahlgrenska University Hospital Gothenburg SwedenUniversity of Gothenburg Gothenburg SwedenObjective The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease‐modifying antirheumatic drugs (bDMARDs) in RA. Methods Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C‐reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Results HR‐pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = −0.38, P = 0.04) and CXCR3+Th17 cells (r = −0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. Conclusion MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.https://doi.org/10.1002/acr2.11742 |
| spellingShingle | Julia M. Scheffler Christina Drevinge Catharina Lindholm Inger Gjertsson Kristina Lend Merete Lund Hetland Mikkel Østergaard Till Uhlig Marte Schrumpf Heiberg Espen A. Haavardsholm Michael T. Nurmohamed Jon Lampa Tuulikki Sokka‐Isler Dan Nordström Kim Hørslev‐Petersen Bjorn Gudbjornsson Gerdur Gröndal Ronald vanVollenhoven Hans Carlsten Mattias Lorentzon Anna‐Karin Hultgård Ekwall Anna Rudin Ulrika Islander Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis ACR Open Rheumatology |
| title | Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis |
| title_full | Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis |
| title_fullStr | Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis |
| title_full_unstemmed | Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis |
| title_short | Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis |
| title_sort | circulating baseline cxcr3 th2 and th17 cell proportions correlate with trabecular bone loss after 48 weeks of biological treatment in early rheumatoid arthritis |
| url | https://doi.org/10.1002/acr2.11742 |
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