Differential renal expression of IFN-α and BAFF and its relevance to disease activity and treatment responsiveness in patients with proliferative lupus nephritis

Abstract

Abstract Background 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 (ISN/RPS class III and IV), five with LN class II, IgA nephropathy, and five with idiopathic hematuria as controls were enrolled. Immunohistochemistry (IHC) for CD3, CD20, interferon-alpha (IFNα), interleukin (IL)-12/p40, and B-cell activating factor (BAFF) was performed. The IHC score was calculated by scoring the number of positive cells/area of the cortex. 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-ds-DNA antibody, 200.9 IU/mL; CH50, 21.9 U/mL; Systemic Lupus Erythematosus 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 IHC score based on the dominancy of IFN-α (n = 17), IL-12 (n = 16), and BAFF group (n = 17) proteins. Hypocomplementemia 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 IHC of IFN-α, IL12, 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.