Serum biomarkers of B-cell activity are differentially expressed in systemic sclerosis (SSc) patients with and without pulmonary arterial hypertension (PAH), according to a study published in Frontiers in Immunology.

Higher median levels of β2-microglobulin (P =.02), serum B-cell maturation antigen (P =.03), serum cluster of differentiation 23 (P =.04), and serum cluster of differentiation 27 (P =.05), as well as lower median levels of immunoglobulin G (IgG; P =.02), were observed in SSc patients with PAH, compared to those without PAH.

Associations between serum levels of B-cell activation markers and clinical markers of pulmonary hypertension were also found during the study. Moderate to strong correlations were observed between B-cell-activating factor and N-terminal prohormone of brain natriuretic peptide (ρ=0.62), the forced vital capacity (FVC)/diffusing capacity of the lung for carbon monoxide (DLCO) ratio (ρ=0.60), and peak tricuspid regurgitation velocity (TRV; ρ=0.45).

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Additionally, peak TRV was moderately correlated with immunoglobulin M levels (ρ=-0.59). The FVC/DLCO ratio was correlated with β2-microglobulin (ρ=0.43) and IgG levels (ρ=-0.41).

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“Soluble markers of B cell activation could be relevant tools to assess organ involvements, disease activity, and severity in SSc patients,” the study authors said.

“Notably, some of them showed interesting associations with PAH, which can plead for a role of B cell activation in the pathogenesis of the pulmonary microangiopathy. B cells could contribute to the SSc vasculopathy through the production of non-Ig angiogenic mediators,” the authors suggested.

The full study initially analyzed biomarker differences between SSc patients and healthy controls before focusing on PAH biomarkers. It recruited 80 SSc patients with a spectrum of clinical manifestations and 80 healthy controls for analysis.

Of the 80 SSc patients, a small subset with limited cutaneous symptoms, no extensive interstitial lung disease, and no previous treatment with immunosuppressants or corticosteroids were chosen to limit bias in the results. This subset included 18 patients with PAH and 18 with no evidence of pulmonary hypertension on screening exams.


Sanges S, Guerrier T, Duhamel A, et al. Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension. Front Immunol. 2022;13:954007. doi:10.3389/fimmu.2022.954007