Predominance of Th1 immune response in diffuse proliferative lupus nephritis

Objective. Lupus nephritis, which shows various histologic patterns, is a s erious complication of systemic lupus erythematosus (SLE). We previously de monstrated the importance of Th1 cell-mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study wa s 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 intracellula r 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 H ealth Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE p atients with WHO class V nephritis (group II; n = 9), and patients with min or glomerular lesions (group III; n = 7). In addition, the histologic activ ity index and chronicity index were evaluated and correlated with the Th1:T h2 ratio. Results. Immunohistochemical studies showed higher numbers of CD68+ macroph ages, CD3+ T cells, and interferon-gamma -positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up-re gulation of expression of osteopontin and CD40, with a small number of infi ltrating T cells expressing interleukin-4. Overall, the Th1:Th2 ratio in gr oup I patients (SLE with DPLN) was high and correlated significantly with t he 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 per ipheral blood Th1:Th2 ratio directly reflects the local histopathologic fin dings. 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.