CD73 B-cell phenotypes and distinct cytokine profiles in patients with active anti-Jo-1 antibody positive idiopathic inflammatory myopathies.

OBJECTIVES

We performed multiparameter phenotyping of peripheral B cells in anti-Jo-1 antibody positive idiopathic inflammatory myopathies (IIM) to delineate disease-associated immunological profiles and the influence of B cells on disease activity.

METHODS

Purified B cells from peripheral blood mononuclear cells from 16 patients with anti-Jo-1 antibody positive IIM (7 with untreated active IIM, 4 with active and treated IIM and 5 with inactive IIM) were analysed by multiparameter spectral flow cytometry. Dimensionality reduction and clustering analysis were applied to pre-gated CD19+B cells. Serum levels of 21 cytokines and anti-Jo-1 IgG autoantibodies were determined. All patients with IIM in this study were positive for anti-Jo-1 antibody.

RESULTS

Anti-Jo-1 antibody levels correlated positively to disease activity. Flow cytometry demonstrated B-cell dysregulation with significantly lower CD73 expression on naïve, switched memory and double negative B cells in patients with active IIM. Clustering analysis further revealed expansions of CD73- IgM+naïve B cells and CD73- CD95+ switched memory B cells in active IIM. In unswitched memory B cells, CD73+CD21+ cells were decreased in active IIM. Patients with active IIM had significantly higher serum levels of B-cell activating factor, inducible protein-10, interleukin-6 and sCD40L which correlated with changes in B-cell populations.

CONCLUSIONS

Since CD73 has an immunoregulatory function by modulating the ATP/adenosine pathway, which is also targeted by methotrexate, the low CD73 B-cell expression in anti-Jo-1 antibody-positive IIM may lead to B-cell hyperactivation. These novel findings further highlight B cells as central in the pathogenesis of IIM and important therapeutic targets.