ARTHRITIS & RHEUMATISM Vol. 54, No. 11, November 2006, pp 3633–3639 DOI 10.1002/art.22192 © 2006, American College of Rheumatology Hepatocyte Growth Factor and Transforming Growth Factor 1 Ratio at Baseline Can Predict Early Response to Cyclophosphamide in Systemic Lupus Erythematosus Nephritis Anna Capuano, 1 Stefano Costanzi, 1 Giusy Peluso, 1 Gianfranco Zannoni, 1 Valerio Gaetano Vellone, 1 Elisa Gremese, 1 Angelo Zoli, 1 Cathryn Scott, 2 Carlo Alberto Beltrami, 2 Giulio Romano, 2 and Gianfranco Ferraccioli 1 Objective. To determine whether the ratio of hepatocyte growth factor (HGF) to transforming growth factor 1 (TGF1) in systemic lupus erythematosus (SLE) nephritis could be a prognostic factor for re- sponse to therapy with cyclophosphamide (CYC) and steroids at 6 months, and to examine whether the molecular ratio of HGF to TGF1 correlates with the activity index (AI) and chronicity index (CI) and has predictive value for remission at the sixth month. Methods. Thirty-six SLE patients with new-onset nephritis, 25 of whom were treated with CYC and steroids, entered into a prospective observational cohort trial at a tertiary university referral center. Renal biopsy findings and clinical parameters were recorded for all patients. Histopathologic, clinical, and immuno- histochemical data at baseline served to define the predictive value for the outcome at 6 months. Results. AI and CI at baseline did not distinguish patients who had achieved remission from those who had not achieved remission after receiving CYC plus steroids. HGF and TGF1 were expressed in the tubuli, not in the glomeruli. The CI correlated directly with the TGF1 extension score (TGF1-ES) (r  0.43, P  0.008), but correlated indirectly with the HGF intensity score (HGF-IS) (r 0.39, P  0.02) and the HGF-ES (r 0.45, P  0.006). An HGF-ES:TGF1-ES ratio of >1 at baseline distinguished patients who had achieved remission from those who had not achieved remission, with a predictive value of 94%. Conclusion. These findings indicate that baseline expression of renal HGF and TGF1 predicts short- term renal outcome after therapy with CYC and ste- roids. One-third of patients with systemic lupus ery- thematosus (SLE) nephritis have flares despite the best treatment and still progress to end-stage renal disease (1–4). Houssiau et al provided clear-cut data from a randomized controlled trial that response to therapy at 6 months was the best predictor of a good long-term renal outcome (5), thus suggesting that the first 6 months could be crucial for future renal function. Among the various other hypotheses, one might be that, at disease onset, kidney tissue biology and pathology could deter- mine major outcomes, such as the response to standard treatment and unrelenting disease progression (6,7), similar to the observation that erosions in rheumatoid arthritis and the biology of those erosions influence the future course of the disease and the response to treat- ment (8). Interstitial damage could be one of the factors determining disease outcome (9). Studies of the role of hepatocyte growth factor (HGF) and transforming growth factor 1 (TGF1) in diabetic nephropathy have highlighted the fundamental role the balance between antifibrogenic/regenerative and profibrogenic/chronicity-inducing factors exerts in the final outcome of the disease (1). HGF plays an important part in tissue repair, proliferation, motility, and differentiation of renal tubular epithelial cells (10,11). In animal models, TGF1 is a potent negative 1 Anna Capuano, MD, Stefano Costanzi, MD, Giusy Peluso, MD, Gianfranco Zannoni, MD, Valerio Gaetano Vellone, MD, Elisa Gremese, MD, Angelo Zoli, MD, Gianfranco Ferraccioli, MD: Cath- olic University of Rome, Rome, Italy; 2 Cathryn Scott, MD, Carlo Alberto Beltrami, MD, Giulio Romano, MD: University of Udine, Udine, Italy. Address correspondence and reprint requests to Gianfranco Ferraccioli, MD, Director, Department of Rheumatology, Catholic University of the Sacred Heart, School of Medicine, Catholic Uni- versity of Rome, Via Moscati 31, 00168 Rome, Italy. E-mail: gf.ferraccioli@rm.unicatt.it. Submitted for publication December 19, 2005; accepted in revised form August 2, 2006. 3633