Significance Of Serum Leptin And Leptin Receptor In Systemic Lupus Erythematosus

Objective:Systemic lupus erythematosus(SLE) is an autoimmune disease characterized by widespread inflammation with possible involvement of any organ and system.There's a high incidence of the disease and poor prognosis,and it is uncurable until now.Recent studies indicated that hormone played an important role in the pathogenesis of SLE.Leptin,a peptide hormone,plays an essential role in the regulation of body weight,neuroendocrine function,reproduction,and the immune response.Recent study indicateed that leptin could promotes the inflammation and immunity.Several studies implicate that leptin could influence the development of type 1 diabetes,rheumatoid arthritis and autoimmune encephalomyelitis in humans by destroying the balance of T lymphocytes.In this study,serum leptin level,leptin receptor level,Th1 and Th2 cells in SLE patients with different stages have been detected to search for correlations between leptin level and pathogenesis of SLE.Methods:43 SLE patients and 12 healthy controls were included in the study(15 newly diagnosed and 28 re-visiting patients),with 7 lupus nephritis(LN) patients.Serum leptin level and soluble leptin receptor level were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA of the long form leptin receptor in human PBMCs were examined by RT-PCR.Peripheral Th cell subsets from patients with SLE were analyzed by flow cytometry.Peripheral T lymphocytes from healthy adult were stimulated in the presence of PHA,or costimulated with leptin and PHA.And the survival cells were evaluated by MTT assay,and Thl,Th2 cells were detected by flow cytometry. Results:1)The mean serum leptin level in SLE patients was 23.71±20.81 ng/ml, higher than the healthy controls(18.82±17.54ng/ml);The mean serum leptin level in LN patients was 30.92±28.39ng/ml,more higher than the healthy controls.2)The soluble leptin receptor level in SLE patients was 6.60±4.42ng/ml,lower than the healthy controls(7.71±1.93ng/ml),and there was significant difference(p=0.007).The soluble leptin receptor level in newly diagnosed patients was 5.62±2.96ng/ml,lower than the healthy controls, and there was significant difference(p=0.007).The soluble leptin receptor level in re-visiting patients was 7.24±5.11ng/ml,higher than newly diagnosed patients.3)The long form leptin receptor was expressed in human PBMCs,and the results of gray scan of PCR production in SLE patients and healthy controls were 1.01±0.92 and 0.88±0.41,but there was no significant difference(p>0.05).4) The percentages of Th,Th1 and Th2 in SLE patients were (4.27±3.18)%,(14.43±12.76)%and(69.97±23.17)%,respectively,lower than the healthy controls((8.14±2.99)%,(22.73±10.37)%,(96.27±2.27)% respectively),p<0.05).The percentage of Th2 in newly diagnosed patients was(58.86±12.03)%,lower than the healthy controls((96.27±2.27)%, p=0.007).The percentages of Th,Th1 and Th2 in re-visiting SLE patients were(3.73±2.25)%,(11.45±8.15)%,(70.96±27.43)%,respectively,lower than the healthy controls(p<0.05).5) After 5 days culture,the OD value of lymphocytes costimulated with leptin and PHA was 0.80±0.02,higher than PHA incubation group(0.69±0.04; p<0.05) and the control group(0.46±0.09).After 3 days culture,The percentages of Th stimulated with high-dose leptin and low dose leptin were (6.82±2.27)%and(5.54±2.04)%,both were higher than the control group(2.29±1.67)%(p<0.05);The percentages of Th1 stimulated with high-dose leptin and low dose leptin were(9.52±2.37)%and(11.50±2.41)%. both were higher than the control group(5.53±2.31)%(p<0.05);The percentage of Th2 stimulated with high-dose leptin and low dose leptin were (19.09±8.96)%and(31.04±3.43)%,both were lower than the control grous (45.6±+7.14)%(p＜0.05).Conclusion:1)Serum leptin level in SLE patients was higher than the healthy controls,especially in LN patients.2)Serum soluble leptin receptor level in SLE patients was lower than the healthy controls.3)The long form of leptin receptor mRNA was detected in human PBMCs.The expression of long form leptin receptors in SLE patients was lightly higher than the healthy controls.4)The percentages of Th,Th1 and Th2 in SLE patients were lower than the healthy controls,especially in the newly diagnosed patients.When re-visiting(after treated with glucocorticoid),the percentage of Th2 increased.The shift towards Th1 cell differentiation in SLE.5)With PHA,leptin could stimulate the proliferation of T cells in vitro, and increase differentiation to Th1 cells.