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Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis

View Article: PubMed Central - PubMed

ABSTRACT

Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.

The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.

The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.

Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.

No MeSH data available.


Related in: MedlinePlus

Colocalization of PTX3 and renal cells markers on kidney sections of patients with active LN (original magnification ×400): (A) The left 2 photos show double staining of CD68 and PTX3, and they failed to be colocalized; The right 2 photos show double staining of CD31 and PTX3. Glomerular endothelial cell, positive for CD31, also showed no expression of PTX3. (B) Double staining of tubular epithelial cell maker, E-cadherin and PTX3 showed no colocation (the arrow indicating the renal tubule). (C) PTX3 and fibroblast marker, α-SMA, colocalized in interstitium, merged in yellow.
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Figure 4: Colocalization of PTX3 and renal cells markers on kidney sections of patients with active LN (original magnification ×400): (A) The left 2 photos show double staining of CD68 and PTX3, and they failed to be colocalized; The right 2 photos show double staining of CD31 and PTX3. Glomerular endothelial cell, positive for CD31, also showed no expression of PTX3. (B) Double staining of tubular epithelial cell maker, E-cadherin and PTX3 showed no colocation (the arrow indicating the renal tubule). (C) PTX3 and fibroblast marker, α-SMA, colocalized in interstitium, merged in yellow.

Mentions: As shown in Figure 4A, CD68, the macrophage cell marker, and PTX3 failed to be colocalized. Glomerular endothelial cell, represented by CD31, also showed no expression of PTX3 (Figure 4A). Double staining for the fibroblast marker, α-smooth muscle actin (α-SMA), and PTX3 showed that PTX3 was mainly colocalized with fibroblast in interstitium, instead of tubular epithelial cell, represented by E-cadherin (Figure 4B and C). The omission of the PTX3-specific primary antibody completely abolished the labeling.


Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis
Colocalization of PTX3 and renal cells markers on kidney sections of patients with active LN (original magnification ×400): (A) The left 2 photos show double staining of CD68 and PTX3, and they failed to be colocalized; The right 2 photos show double staining of CD31 and PTX3. Glomerular endothelial cell, positive for CD31, also showed no expression of PTX3. (B) Double staining of tubular epithelial cell maker, E-cadherin and PTX3 showed no colocation (the arrow indicating the renal tubule). (C) PTX3 and fibroblast marker, α-SMA, colocalized in interstitium, merged in yellow.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998266&req=5

Figure 4: Colocalization of PTX3 and renal cells markers on kidney sections of patients with active LN (original magnification ×400): (A) The left 2 photos show double staining of CD68 and PTX3, and they failed to be colocalized; The right 2 photos show double staining of CD31 and PTX3. Glomerular endothelial cell, positive for CD31, also showed no expression of PTX3. (B) Double staining of tubular epithelial cell maker, E-cadherin and PTX3 showed no colocation (the arrow indicating the renal tubule). (C) PTX3 and fibroblast marker, α-SMA, colocalized in interstitium, merged in yellow.
Mentions: As shown in Figure 4A, CD68, the macrophage cell marker, and PTX3 failed to be colocalized. Glomerular endothelial cell, represented by CD31, also showed no expression of PTX3 (Figure 4A). Double staining for the fibroblast marker, α-smooth muscle actin (α-SMA), and PTX3 showed that PTX3 was mainly colocalized with fibroblast in interstitium, instead of tubular epithelial cell, represented by E-cadherin (Figure 4B and C). The omission of the PTX3-specific primary antibody completely abolished the labeling.

View Article: PubMed Central - PubMed

ABSTRACT

Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.

The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.

The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.

Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.

No MeSH data available.


Related in: MedlinePlus