Background Glucocorticoids (GCs) were the essential drugs for systemic lupus erythematosus (SLE). However, different patients differ substantially in their response to GCs treatment. Our current study aims at investigating whether climate variability and climate-gene interaction influence SLE patients' response to the therapy of GCs.

Methods In total, 778 SLE patients received therapy of GCs for a study of 12-week follow-up. The efficacy of GCs treatment was evaluated using the Systemic Lupus Erythematosus Disease Activity Index. The climatic data were provided by China Meteorological Data Service Center. Additive and multiplicative interactions were examined.

Results Compared with patients with autumn onset, the efficacy of GCs in patients with winter onset is relatively poor (ORadj = 1.805, 95%CIadj: 1.181–3.014, padj = 0.020). High mean relative humidity during treatment decreased the efficacy of GCs (ORadj = 1.033, 95%CIadj: 1.008–1.058, padj = 0.011), especially in female (ORadj = 1.039, 95%CIadj: 1.012–1.067, padj = 0.004). There was a significant interaction between sunshine during treatment and TRAP1 gene rs12597773 on GCs efficacy (Recessive model: AP = 0.770). No evidence of significant interaction was found between climate factors and the GR gene polymorphism on the improved GCs efficacy in the additive model. Multiplicative interaction was found between humidity in the month prior to treatment and GR gene rs4912905 on GCs efficacy (Dominant model: OR = 0.470, 95%CI: 0.244–0.905, p = 0.024).

Conclusions Our findings suggest that climate variability influences SLE patients' response to the therapy of GCs. Interactions between climate and TRAP1/GR gene polymorphisms were related to GCs efficacy. The results guide the individualized treatment of SLE patients.