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Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study

Hamberg, Viggo ; Sohrabian, Azita ; Volkmann, Elizabeth R ; Wildt, Marie LU ; Löfdahl, Anna LU ; Wuttge, Dirk M LU ; Hesselstrand, Roger LU ; Dellgren, Göran ; Westergren-Thorsson, Gunilla LU orcid and Rönnelid, Johan , et al. (2023) In Arthritis Research & Therapy 25. p.1-13
Abstract

BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.

METHODS: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times... (More)

BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.

METHODS: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.

RESULTS: Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.

CONCLUSIONS: This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Lung Diseases, Interstitial, Scleroderma, Systemic/complications, Autoantibodies, Pulmonary Fibrosis, Scleroderma, Diffuse
in
Arthritis Research & Therapy
volume
25
article number
162
pages
1 - 13
publisher
BioMed Central (BMC)
external identifiers
  • pmid:37667402
  • scopus:85169847122
ISSN
1478-6354
DOI
10.1186/s13075-023-03141-4
language
English
LU publication?
yes
additional info
© 2023. BioMed Central Ltd., part of Springer Nature.
id
52cc3349-20f0-4618-b7ea-ce3c670802b8
date added to LUP
2023-09-08 09:28:43
date last changed
2025-10-20 14:24:28
@article{52cc3349-20f0-4618-b7ea-ce3c670802b8,
  abstract     = {{<p>BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.</p><p>METHODS: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.</p><p>RESULTS: Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p &lt; 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.</p><p>CONCLUSIONS: This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.</p>}},
  author       = {{Hamberg, Viggo and Sohrabian, Azita and Volkmann, Elizabeth R and Wildt, Marie and Löfdahl, Anna and Wuttge, Dirk M and Hesselstrand, Roger and Dellgren, Göran and Westergren-Thorsson, Gunilla and Rönnelid, Johan and Andréasson, Kristofer}},
  issn         = {{1478-6354}},
  keywords     = {{Humans; Lung Diseases, Interstitial; Scleroderma, Systemic/complications; Autoantibodies; Pulmonary Fibrosis; Scleroderma, Diffuse}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{1--13}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research & Therapy}},
  title        = {{Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study}},
  url          = {{http://dx.doi.org/10.1186/s13075-023-03141-4}},
  doi          = {{10.1186/s13075-023-03141-4}},
  volume       = {{25}},
  year         = {{2023}},
}