Peripheral immune profiles separate disease activity stages in birdshot uveitis
- 1Berlin Institute of Health at Charité – Universitätsmedizin Berlin , ,
- 2BIH Center of Immunomics, BIH, Berlin Institute of Health at Charité - Universitätsmedizin Berlin , ,
- 3Department of Ophthalmology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , ,
Abstract
Introduction: Birdshot uveitis (BU) is a chronic, debilitating posterior uveitis strongly associated with HLA-A*29, supporting a suspected autoimmune etiology. We used high-dimensional mass cytometry and clinical stratification to characterize the peripheral immune landscape in BU and identify disease activity-dependent signatures.
Methods: In this cross-sectional study, we included 36 treated BU patients and 31 age- and sex-matched healthy controls (HCs). All participants underwent comprehensive ophthalmologic evaluation with multimodal imaging. Patients were stratified by an expert ophthalmologist into Inactive, Active, and Burned-out disease activity groups based on clinical and imaging findings. Peripheral blood and serum were collected for immunoprofiling using a 37-marker mass cytometry panel and multiplex cytokine analysis.
Results: Compared with HCs, BU patients showed increased frequencies of Th17 cells, CD146 ⁺ T cells, CXCR3 ⁺ CCR4 ⁺ intermediate effector/central memory T cells, CD56 dim natural killer (NK) cells, and elevated serum IL-18. Disease activity-specific differences were evident. Inactive patients displayed more quiescent effector T cell phenotypes, including higher frequencies of TIM-3 ⁺ Tc17-Tc22 intermediates and CD8 ⁺ T memory stem cells (T SCM ), capable of maintaining long-term immune and autoimmune memory. Active patients exhibited increased in vivo activation of Th17 and Tc1 subsets (elevated HLA-DR, CD38, and PD-1 expression) and the highest levels of CD56 dim NK cells. Immune profiles were also linked to current treatment: conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were associated with higher CD56 bright NK cell frequencies, while absence of current therapy correlated with elevated PD-1 ⁺ /SLAMF7 ⁺ Tc17+1 and PD-1 ⁺ CD57 ⁺ CD8 ⁺ terminally differentiated effector memory T cells re-expressing CD45RA (T EMRA ). Tocilizumab treatment resulted in apparent loss of IL-6R ⁺ T cells and an increase in SLAMF7 ⁺ T cells, consistent with epitope masking by the therapeutic antibody.
Discussion: Integrated peripheral immune profiling with clinical stratification revealed distinct disease activity-dependent and treatment-associated signatures in BU. Inactive and Burned-out patients showed predominantly exhausted or anergic T cell phenotypes, whereas active disease featured heightened T cell activation and mature NK cell expansion. These findings demonstrate both the value and challenges of interpreting immune profiles in treated patients, especially with biologics such as tocilizumab that alter receptor detectability. Despite the heterogeneity typical of rare-disease cohorts, activity-associated immune patterns were detectable. Future studies should evaluate the diagnostic, prognostic, and monitoring utility of these signatures in BU.
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BibTeX
@article{pohlmannkrappitz2026peripheral,
title = {{Peripheral immune profiles separate disease activity stages in birdshot uveitis}},
author = {D. Pohlmann-Krappitz and I. Kaeferstein and B. Kruse and S. Winterhalter and A. Thiel and U. Pleyer and J. Braun},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1938305},
url = {https://europepmc.org/article/PMC/PMC13672581},
note = {CC BY},
}
RIS
TY - JOUR
TI - Peripheral immune profiles separate disease activity stages in birdshot uveitis
AU - D. Pohlmann-Krappitz
AU - I. Kaeferstein
AU - B. Kruse
AU - S. Winterhalter
AU - A. Thiel
AU - U. Pleyer
AU - J. Braun
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1938305
UR - https://europepmc.org/article/PMC/PMC13672581
AB - Introduction: Birdshot uveitis (BU) is a chronic, debilitating posterior uveitis strongly associated with HLA-A*29, supporting a suspected autoimmune etiology. We used high-dimensional mass cytometry and clinical stratification to characterize the peripheral immune landscape in BU and identify disease activity-dependent signatures. Methods: In this cross-sectional study, we included 36 treated BU patients and 31 age- and sex-matched healthy controls (HCs). All participants underwent comprehensive ophthalmologic evaluation with multimodal imaging. Patients were stratified by an expert ophthalmologist into Inactive, Active, and Burned-out disease activity groups based on clinical and imaging findings. Peripheral blood and serum were collected for immunoprofiling using a 37-marker mass cytometry panel and multiplex cytokine analysis. Results: Compared with HCs, BU patients showed increased frequencies of Th17 cells, CD146 ⁺ T cells, CXCR3 ⁺ CCR4 ⁺ intermediate effector/central memory T cells, CD56 dim natural killer (NK) cells, and elevated serum IL-18. Disease activity-specific differences were evident. Inactive patients displayed more quiescent effector T cell phenotypes, including higher frequencies of TIM-3 ⁺ Tc17-Tc22 intermediates and CD8 ⁺ T memory stem cells (T SCM ), capable of maintaining long-term immune and autoimmune memory. Active patients exhibited increased in vivo activation of Th17 and Tc1 subsets (elevated HLA-DR, CD38, and PD-1 expression) and the highest levels of CD56 dim NK cells. Immune profiles were also linked to current treatment: conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were associated with higher CD56 bright NK cell frequencies, while absence of current therapy correlated with elevated PD-1 ⁺ /SLAMF7 ⁺ Tc17+1 and PD-1 ⁺ CD57 ⁺ CD8 ⁺ terminally differentiated effector memory T cells re-expressing CD45RA (T EMRA ). Tocilizumab treatment resulted in apparent loss of IL-6R ⁺ T cells and an increase in SLAMF7 ⁺ T cells, consistent with epitope masking by the therapeutic antibody. Discussion: Integrated peripheral immune profiling with clinical stratification revealed distinct disease activity-dependent and treatment-associated signatures in BU. Inactive and Burned-out patients showed predominantly exhausted or anergic T cell phenotypes, whereas active disease featured heightened T cell activation and mature NK cell expansion. These findings demonstrate both the value and challenges of interpreting immune profiles in treated patients, especially with biologics such as tocilizumab that alter receptor detectability. Despite the heterogeneity typical of rare-disease cohorts, activity-associated immune patterns were detectable. Future studies should evaluate the diagnostic, prognostic, and monitoring utility of these signatures in BU.
SN - 1664-3224
ER -