Background: The prognostic factors of lupus nephritis are still not completely known. Several animal models demonstrate that hepatocyte growth factor (HGF) and transforming growth factor (TGF-β1) are implicated in renal damage. Moreover, recent studies have revealed the implication of mononuclear cells interstitial infiltrate in the pathogenesis and prognosis of SLE nephritis. Objectives: To determine whether immune cell infiltrate and HGF/TGFβ1 expression could have prognostic value in assessing SLE nephritis response to therapy. Methods: 42 consecutive patients with newly diagnosed lupus nephritis were included in the study and underwent renal biopsy. Immunohistochemical renal expression of HGF and TGFβ1 (in all the kidney samples) and of different immune cellular types (CD3,CD8, CD20, CD68, CD138, Pax-5, in 31 kidney samples) was analyzed. Expression of HGF and TGFβ1 was evaluated following the Mizuno score (1). Cellular count was performed for each phenotype and results were expressed as number of positive cells per square millimeter. The infiltrate was considered as present if the number of total infiltrating lymphocytes was > 10 cells. Patients were divided in responder (R) and non responder (NR) subgroups on the basis of 24h proteinuria < 1 gr and ameliorated creatinine levels from baseline after six months of therapy. Results: Characteristics of the 42 patients are: 35 women, 7 men; mean ± SD age at renal biopsy 36.1±11.9; mean disease duration 4.9±4.9; number of class II WHO nephritis = 2; class III WHO = 1; class IV WHO = 38; class V WHO = 1; mean activity index 8.0±4.4 and chronicity index 2.7±2.4. The 29 responder patients had higher HGF extension score (p<0.001) and intensity score (p<0.001) and HGF/TGFβ1 ratio either for extension (p<0.001) and intensity score (p=0.001) than the 13 non responder patients. Chronicity index directly correlates with TGFβ1 extension score (r=0.40, p=0.03) and with the presence of T cells CD3+ (r=0.5, p=0.004), CD8+ (r=0.36, p=0.04) and Pax5+ cells (r=0.40, p=0.02). The presence of inflammatory infiltrate (87.5% in NR, vs 43.5% in R p=0.04) and the number of CD3+ cells were significantly higher in non responder patients than in responder. On the logistic regression analysis, the only parameter predictive of response was the HGF/TGFβ1 extension score (OR 16.2, 95% CIs 2.5-112.3). Conclusion: These data support the hypothesis that the HGF/TGFβ1 ratio at baseline seems to identify patients with a good response to standard SLE therapy and that cell-mediated immunity could play a central role in determine SLE nephritis course. The higher values of chronicity index observed in patients with infiltrates suggest the possible role in the progression of nephritis and of the chronic damage. References: 1. Mizuno S, Matsumoto K, Kurosawa T, Mizuno-Horikawa Y, Nakamura T. Reciprocal balance of HGF and TGFβ1 in renal fibrosis in mice. Kidney Int 2000, 57: 937-48.
Clinical nephritis remission is influenced by hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGFβ1) renal tubular expression more than interstitial cell infiltrate in systemic lupus erythematosus (SLE) patients
Gremese E;
2008-01-01
Abstract
Background: The prognostic factors of lupus nephritis are still not completely known. Several animal models demonstrate that hepatocyte growth factor (HGF) and transforming growth factor (TGF-β1) are implicated in renal damage. Moreover, recent studies have revealed the implication of mononuclear cells interstitial infiltrate in the pathogenesis and prognosis of SLE nephritis. Objectives: To determine whether immune cell infiltrate and HGF/TGFβ1 expression could have prognostic value in assessing SLE nephritis response to therapy. Methods: 42 consecutive patients with newly diagnosed lupus nephritis were included in the study and underwent renal biopsy. Immunohistochemical renal expression of HGF and TGFβ1 (in all the kidney samples) and of different immune cellular types (CD3,CD8, CD20, CD68, CD138, Pax-5, in 31 kidney samples) was analyzed. Expression of HGF and TGFβ1 was evaluated following the Mizuno score (1). Cellular count was performed for each phenotype and results were expressed as number of positive cells per square millimeter. The infiltrate was considered as present if the number of total infiltrating lymphocytes was > 10 cells. Patients were divided in responder (R) and non responder (NR) subgroups on the basis of 24h proteinuria < 1 gr and ameliorated creatinine levels from baseline after six months of therapy. Results: Characteristics of the 42 patients are: 35 women, 7 men; mean ± SD age at renal biopsy 36.1±11.9; mean disease duration 4.9±4.9; number of class II WHO nephritis = 2; class III WHO = 1; class IV WHO = 38; class V WHO = 1; mean activity index 8.0±4.4 and chronicity index 2.7±2.4. The 29 responder patients had higher HGF extension score (p<0.001) and intensity score (p<0.001) and HGF/TGFβ1 ratio either for extension (p<0.001) and intensity score (p=0.001) than the 13 non responder patients. Chronicity index directly correlates with TGFβ1 extension score (r=0.40, p=0.03) and with the presence of T cells CD3+ (r=0.5, p=0.004), CD8+ (r=0.36, p=0.04) and Pax5+ cells (r=0.40, p=0.02). The presence of inflammatory infiltrate (87.5% in NR, vs 43.5% in R p=0.04) and the number of CD3+ cells were significantly higher in non responder patients than in responder. On the logistic regression analysis, the only parameter predictive of response was the HGF/TGFβ1 extension score (OR 16.2, 95% CIs 2.5-112.3). Conclusion: These data support the hypothesis that the HGF/TGFβ1 ratio at baseline seems to identify patients with a good response to standard SLE therapy and that cell-mediated immunity could play a central role in determine SLE nephritis course. The higher values of chronicity index observed in patients with infiltrates suggest the possible role in the progression of nephritis and of the chronic damage. References: 1. Mizuno S, Matsumoto K, Kurosawa T, Mizuno-Horikawa Y, Nakamura T. Reciprocal balance of HGF and TGFβ1 in renal fibrosis in mice. Kidney Int 2000, 57: 937-48.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
