Ectopic lymphoid structures (ELSs) can form in the salivary glands of patients with Sjögren syndrome, and are thought to contribute to pathology. Previous studies have implicated the CD40–CD40 ligand (CD40L) pathway in ELS formation and function. In a new study from a group at the Novartis Institutes for Biomedical Research, therapeutic blockade of CD40L ameliorated disease in a non-obese diabetic (NOD) mouse model of secondary Sjögren syndrome.

Credit: Springer Nature Limited

“We found evidence of chronic CD40 expression and pathway activation in the salivary glands of these mice, indicating that signalling downstream of this receptor could have a function in Sjögren syndrome disease progression,” states corresponding author James Rush.

The researchers treated the mice biweekly with an anti-CD40L antibody (MR1) from 12 weeks of age, at which stage the mice develop focal cellular infiltrates. The treatment inhibited sialadenitis, reduced the number of infiltrating lymphocytes and macrophages, as well as the number of ELSs, and suppressed autoantibody production in these mice.

By contrast, the treatment had no effect on the expression of the water channel protein AQP5 in the salivary glands. This protein is involved in regulating saliva and tear production but whether it is a useful surrogate marker of salivary gland function in Sjögren syndrome is unclear.

The treatment inhibited sialadenitis … and suppressed autoantibody production

“Collectively, our data suggest that therapeutic blockade of the CD40–CD40L costimulatory pathway could provide a beneficial therapeutic effect in patients with Sjögren syndrome, a notion confirmed in a recent Phase II study clinical study of the anti-CD40 monoclonal antibody Iscalimab (CFZ533),” says Rush. “Future work could focus on how CD40 blockade affects salivary gland function, as well as whether chronic therapeutic dosing is required for a disease modifying effect.”