Predominance of Th1 immune response in diffuse proliferative lupus nephritis

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Abstract
Objective Lupus nephritis, which shows various histologic patterns, is a serious complication of systemic lupus erythematosus (SLE). We previously demonstrated the importance of Th1 cell–mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study was to examine the relationship between the peripheral blood Th1/Th2 balance and the intrarenal immune response. Methods The Th1:Th2 ratio in peripheral blood was measured by intracellular staining for cytokines with flow cytometry. Immunohistochemical analysis of renal biopsy specimens was performed to clarify the characterization of local infiltrating cells in 3 groups of subjects: SLE patients with World Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE patients with WHO class V nephritis (group II; n = 9), and patients with minor glomerular lesions (group III; n = 7). In addition, the histologic activity index and chronicity index were evaluated and correlated with the Th1:Th2 ratio. Results Immunohistochemical studies showed higher numbers of CD68+ macrophages, CD3+ T cells, and interferon‐γ–positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up‐regulation of expression of osteopontin and CD40, with a small number of infiltrating T cells expressing interleukin‐4. Overall, the Th1:Th2 ratio in group I patients (SLE with DPLN) was high and correlated significantly with the histologic activity index, but not with the chronicity index. Conclusion We have identified a predominance of Th1‐type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Th1:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Th1 response.