Differential expression of IFN-α, IL-12 and BAFF on renal immune cells and its relevance to disease activity and treatment responsiveness in patients with proliferative lupus nephritis

Abstract

Objective Since molecularly targeted therapies are emerging for treating lupus nephritis (LN), this study aimed to assess the immunohistochemical findings of the cytokines in renal tissue and their pathological and clinical relevance in LN.Methods Fifty patients with proliferative LN formed the case group; 5 with LN class II, IgA nephropathy and 10 with idiopathic haematuria were enrolled as controls. Immunohistochemical analysis for CD3, CD20, interferon (IFN)-α, interleukin (IL)-12/p40 and B-cell activating factor (BAFF) was performed by scoring the number of positive cells/area of the cortex. All immunohistochemical investigations were performed on formalin-fixed paraffin-embedded renal tissue. Proliferative LN cases were grouped by the dominant expression of IFN-α, IL-12/p40 and BAFF, and subsequently, clinicopathological features were compared.Results Clinical data of patients with proliferative LN included urine protein creatinine ratio, 2.2 g/gCre; anti-double-stranded DNA antibody, 200.9 IU/mL; total complement activity (CH50), 21.9 U/mL and SLE Disease Activity Index, 19.8 points. Proliferative LN cases, including class III (n=18) and IV (n=32), were classified into three subgroups according to the immunohistochemical score based on the dominancy of IFN-α (n=17), IL-12 (n=16) and BAFF group (n=17) proteins. Hypocomplementaemia and glomerular endocapillary hypercellularity were significantly increased in the IFN-α group, whereas chronic lesions were significantly higher in the IL-12 group (p<0.05). The IFN-α group had a poorer renal prognosis in treatment response after 52 weeks.Conclusions The immunohistochemistry (IHC) of IFN-α, IL-12 and BAFF for proliferative LN enabled grouping. Especially, the IFN-α and IL-12 groups showed different clinicopathological features and renal prognoses. The results indicated the possibility of stratifying cases according to the IHC of target molecules, which might lead to precision medicine.