Increased L-Selectin on Monocytes Is Linked to the Autoantibody Profile in Systemic Sclerosis

Abstract

Monocytes are known to be implicated in the pathogenesis of systemic sclerosis (SSc), as they exert prominent migratory, adhesive, and chemotactic properties. The aim of our study was to characterize the surface expression of adhesion/chemotactic molecules (CD62L, CD11b, CCR2, CCR5) on the SSc monocytes and determine correlations with the clinical presentation of SSc. We included 38 SSc patients and 36 healthy age-and sex-matched controls. Isolated monocytes, as well as in vitro serum-treated monocytes, were analyzed by flow cytometry; additionally, soluble CD62L was measured in serum. We found increased soluble CD62L in the SSc serum samples and increased CD62L on the surface of the SSc monocytes in the in the same set of patients. Among samples with determined SSc-specific autoantibodies, the surface CD62L was the lowest in patients positive for anti-PM/Scl autoantibodies and the highest in patients with anti-topoisomerase I autoantibodies (ATA). The treatment of isolated healthy monocytes with ATA-positive SSc serum resulted in increased surface CD62L expression. Moreover, surface CCR5 was reduced on the monocytes from SSc patients with interstitial lung disease but also, along with CCR2, negatively correlated with the use of analgesics/anti-inflammatory drugs and immunosuppressants. In conclusion, increased CD62L on SSc monocytes, particularly in ATA-positive patients, provides new insights into the pathogenesis of SSc and suggests CD62L as a potential therapeutic target.