Title :

Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension.

Author(s) :

Sanges, Sébastien [Auteur]
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guerrier, Thomas [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Duhamel, Alain [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Guilbert, Lucile [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Hauspie, Carine [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Largy, Alexis [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Balden, Maité [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Podevin, Céline [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lefevre, Guillaume [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Jendoubi, Manel [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Speca, Silvia [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Hachulla, Eric [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Sobanski, Vincent [Auteur]
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Dubucquoi, Sylvain [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Launay, David [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Journal title :

Frontiers in Immunology

Abbreviated title :

Front Immunol

Volume number :

13

Pages :

954007

Publication date :

2022-08-16

ISSN :

1664-3224

English keyword(s) :

systemic sclerosis
pulmonary arterial hypertension
B cell
humoral immunity
angiogenesis
pro-angiogenic factors
soluble markers
BAFF

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Introduction: Soluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease ...
Show more >Introduction: Soluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics. Methods: 1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant. Results: In a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC. Conclusion: Soluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2023-11-15T03:32:04Z
2024-04-15T09:33:10Z