Background and Aims

Primary Membranous Nephropathy (MN) is a rare autoimmune renal disease associated with autoantibodies to PLA2R1 (70%), THSD7A (3%) or NELL1 (15%). A Chinese study showed an association between exposure to high levels of PM_2.5 and an increased risk of MN. The role of Th17 has been demonstrated in the pathogenesis of primary nephrotic syndrome in children, asthma or allergic contact dermatitis. Interaction with the environment seems to be important for the pathophysiology of MN but the link with cytokine profile has never been demonstrated.

We aim to correlate the cytokine profile of MN patients with environmental data.

Methods

Patients completed a questionnaire about their lifestyle habits. Environmental data was assessed by a geographer. Concentration of cytokines in the serum after nonspecific stimulation of T and NK cells with immune ligands was measured using Th1/Th2/Th9/Th17 18-Plex ProcartaPlex Panel (ThermoFisher Scientific).

Results

Fifty-seven patients with active MN and 27 healthy donors were included. MN patients had higher rates of IL-17A and IL-6 (p=0.036 and p=0.003, respectively), and deficiency of IL-10, IFN-γ and IL-12p70 (p=0.053, p=0.002 and p<0.0001, respectively), suggesting activation of Th17 pathway and a deficiency of Th1 and Treg pathways.

Patients with high level of IL-17A lived mostly in urban areas (82% vs 56%, p=0.033), worked in an office (46% vs 12%, p=0.006), were atopic (64% vs 38%, p=0.058) and had their first symptoms in spring (p=0.056). They had more venous thromboembolic events (p=0.032) and relapses (p=0.012).

Conclusions

MN patients have Th17-mediated inflammation related to an urban environment and atopic profile that probably induces immunization.