INTRODUCTION AND AIMS: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus. T lymphocytes with regulatory properties (Tregs) play a role in preventing autoimmunity, are involved in LN pathogenesis and may also determine glomerular lesions in LN. Their potential use as LN biomarkers is investigated. The aim of our study was to assess the relationship between repeated measurements of Tregs proportions, histopathology classes and five-year clinical outcomes in LN patients with different disease duration and activity.

METHODS: Forty eight LN patients were followed-up for 5 years. Their mean age, disease duration and activity (SLEDAI) at baseline was 41.1 years, 9.8 years and 8.3 points, respectively. Their blood was collected twice: at baseline and after 6 months. Populations of Tregs and Th17 cells were analysed by flow cytometry, in relation to clinical parameters and previously established LN classes assessed according to the ISN/RPS 2003 classification.

RESULTS: Lymphocytes percentages in class IV were different from classes III, V or a combination of III and V. In the latter classes, the percentages of the Tregs and Th17 cells were significantly lower, whereas in class IV the increase in FOXP3 in the Tregs and Th17 cells over six months period was significantly higher (Table 1). Changes in glomerular filtration rate and SLEDAI within 5 years did not correlate with single or repeated Tregs measurements.

CONCLUSIONS: Differences in lymphocyte proportions between class IV and other classes may suggest its distinct pathogenesis and warrants further investigations on their role as LN biomarker.

Factors differentiating histopathology LN classes.

Class of LN vs other classesCorrelating factorp
III + VC4↓0,0007
FOXP3% in CD4+CD25+↓0,009
FOXP3 MFI in CD4+CD25+↓0,00003
FOXP3 MFI in CD4+↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IIIFOXP3 MFI in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IVFOXP3% in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high â†‘0,02
FOXP3% in CD4+CD25+CD127+↓0,03
delta FOXP3% in CD4+CD25+CD127+ â†‘0,003
VFOXP3 MFI in CD4+CD25+↓0,0006
Class of LN vs other classesCorrelating factorp
III + VC4↓0,0007
FOXP3% in CD4+CD25+↓0,009
FOXP3 MFI in CD4+CD25+↓0,00003
FOXP3 MFI in CD4+↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IIIFOXP3 MFI in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IVFOXP3% in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high â†‘0,02
FOXP3% in CD4+CD25+CD127+↓0,03
delta FOXP3% in CD4+CD25+CD127+ â†‘0,003
VFOXP3 MFI in CD4+CD25+↓0,0006

Factors differentiating histopathology LN classes.

Class of LN vs other classesCorrelating factorp
III + VC4↓0,0007
FOXP3% in CD4+CD25+↓0,009
FOXP3 MFI in CD4+CD25+↓0,00003
FOXP3 MFI in CD4+↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IIIFOXP3 MFI in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IVFOXP3% in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high â†‘0,02
FOXP3% in CD4+CD25+CD127+↓0,03
delta FOXP3% in CD4+CD25+CD127+ â†‘0,003
VFOXP3 MFI in CD4+CD25+↓0,0006
Class of LN vs other classesCorrelating factorp
III + VC4↓0,0007
FOXP3% in CD4+CD25+↓0,009
FOXP3 MFI in CD4+CD25+↓0,00003
FOXP3 MFI in CD4+↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IIIFOXP3 MFI in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high↓0,02
FOXP3 MFI in CD4+CD25+CD127+↓0,01
IVFOXP3% in CD4+CD25high↓0,03
delta FOXP3% in CD4+CD25high â†‘0,02
FOXP3% in CD4+CD25+CD127+↓0,03
delta FOXP3% in CD4+CD25+CD127+ â†‘0,003
VFOXP3 MFI in CD4+CD25+↓0,0006

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