Role Of Innate Immunity In IgA Nephropathy

Objective:To investigate the expression of innate immunity components Toll-like receptor (TLR) and its ligand MYD88in human tissues of IgA nephropathy.Methods:The experimental study was divided into two groups:1) the control group (n=13):nephrectomized tissues from patients diagnosed as renal carcinoma (away from cancer tissue>5cm);2) IgA nephropathy group (n=94):renal biopsy specimens from YanBian University Hospital and the First Affiliated Hospital of JiLin university during5years. According to the lee’s grade system, IgA nephropathy group further divided into five subgroups: grade1(n=17)、grade2(n=23)、grade3(n=23)、grade4(n=18)、grade5(n=13). Demographic and clinical characteristics such as age, systolic blood pressure (SBP), serum creatinine, estimated glomerular filtration rate (eGFR), serum albumin, and24h urinary protein excretion were recorded. Intrarenal expression of TLRs and MYD88were evaluated by immunohistochemistry, and the results was semiquantified using the TDI Scope Eye version3.5(Olympus, Japan) image analysis system as bellows:glomerulus, analysis renal biopsy specimens and corresponding glomeruli in normal tissues and the results was averaged (%/mm); tubulointerstitum:a minimum of20unoverlapped fields in each specimens (except glomeruli) was assessed (%/mm). The Pearson single-correlation coefficient was used to compare TLRs expression with24h urinary protein excretion and eGFR.Results:Compared with the control group, IgA nephropathy patients showed a significant increase in the expression of TLR2and TLR4in the glomeruli (TLR2:99.70±3.77%/mm2vs.30.92±3.70%/mm2; TLR4:118.78±7.84%/mm2vs.30.71±7.01%/mm2, P<0.01). However, there is no relationship between TLRs expression and the degree of morphologic renal damage. Interestingly, TLR2expression was significantly increased in the tubulointerstitum of IgA nephropathy (118.78±7.84%/mm2vs.30.71±7.01%/mm2, P<0.01) although TLR4expression was unaffected. Concomitantly, this increase in TLRs expression was in parallel with overexpression of its ligand MYD88(glomerulus:168.72±11.30%/mm2vs.98.11±8.21%/mm2, P<0.01; tubulointerstitum:43.14±1.80%/mm2vs.17.16±1.50%/mm2, P<0.01). Furthermore, the expression of TLRs protein was positively correlated with24h urinary protein excretion (TLR2:r=0.363;TLR4:r=0.328, P<0.05) and negatively correlated with the eGFR (TLR2:-0.435;TLR4:-0.352, P<0.05).Conclusion:TLRs and MYD88expression is upregulated in IgA nephropathy, and that this increase strongly correlated with24h urinary protein excretion and eGFR. These findings suggest that the innate immunity may be one of the molecular mechanisms participates in human IgA nephropathy.