CN108982866A - Urinate purposes of the Tenascin-C than creatinine in preparation diagnosis and prognosis evaluation idiopathic IgA nephrosis preparation - Google Patents
Urinate purposes of the Tenascin-C than creatinine in preparation diagnosis and prognosis evaluation idiopathic IgA nephrosis preparation Download PDFInfo
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- CN108982866A CN108982866A CN201710415604.6A CN201710415604A CN108982866A CN 108982866 A CN108982866 A CN 108982866A CN 201710415604 A CN201710415604 A CN 201710415604A CN 108982866 A CN108982866 A CN 108982866A
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Abstract
The invention belongs to the diagnosis of molecular biology marker and prognosis evaluation fields, it is related to urinating purposes of the Tenascin-C than creatinine in preparation diagnosis and prognosis evaluation idiopathic IgA nephrosis preparation, the urine Tenascin-C can be used for diagnosing the disease severity and prognosis evaluation of idiopathic IgA nephrosis than creatinine (uTNC/Cr) as marker.The present invention is by detection urine Tenascin-C than creatinine level, and idiopathic IgA nephrotic uTNC/Cr level is higher than normal person as the result is shown, and urinating TNC is by being excreted with urine after the lesions expression such as segment hardening bead, crescent in nephridial tissue；Meanwhile uTNC/Cr level can reflect glomerulus TNC expression quantity, reflects the lesion severity of IgA nephrosis, can assist the prognosis evaluation of IgA nephrosis indirectly.The present invention provides detect time saving, sensitivity than the prior art and accuracy is higher, cost is lower, and/or the preparation of more efficient diagnosis and prognosis evaluation idiopathic IgA nephrosis or for the kit of these applications.
Description
Technical field
The invention belongs to the diagnosis of molecular biology marker and prognosis evaluation fields, and in particular to urine Tenascin-C compares creatinine
Purposes in preparation diagnosis and prognosis evaluation idiopathic IgA nephrosis preparation, the urine Tenascin-C is than creatinine (uTNC/
Cr it) can be used for diagnosing the disease severity and prognosis evaluation of idiopathic IgA nephrosis as marker.
Background technique
It is that China glomerulus source property blood urine is most common prior art discloses IgA nephrosis (IgA nephropathy, IgAN)
The cause of disease, any age can be betided；Patient groups' quantity is big, distribution is wide, heterogeneous.Claim 15~40%IgA nephrosis according to investigations
Patient can be after diagnosis in 20~25 years to End-stage renal disease (ESRD).There is the pathogenesis of studies have shown that IgA nephrosis
It is not fully understood at present, interindividual clinical manifestation, laboratory check and renal biopsy changes heterogeneity by force.At present
In clinical practice, the diagnosis of IgA nephrosis depends on single renal biopsy, further according to 4 pathology of Oxford parting " MEST "
The pathology severity and prognosis of metrics evaluation IgA nephrosis, still, practice display, single renal biopsy tissue amount rareness, it is seen that
Glomerulus Limited Number, it is thus impossible to reflect Renal tissues damage degree comprehensively；Moreover, as invasive operation, it is impossible to be used in
The follow-up therapeutic evaluation of IgA nephrosis and the monitoring of disease dynamic progress speed；Even if clinic is by biochemistry such as " serum creatinines " at present
Index reflects renal function, but its sensibility is poor, influence factor is more, and when serum creatinine increases, kidney has had more than 50% glomerulus
Discarded, lesion is very serious, in a short time i.e. can be to the terminal phase, therefore, and early diagnosis is not achieved in above-mentioned detection means
With the purpose of intervention.
Tenascin-C (TNC) belongs to extracellular matrix glycoprotein, polypeptide chain molecular weight about 220~330kDa, it
The expression of embryonic development period height, and strictly regulated and controled, and it is almost undetectable in normal adult tissue；Related studies have shown that
Tissue, serum T NC expression up-regulation are usually related with the morbid states such as inflammation, damage, tumor neogenetic, at tissue (heart, lung, liver)
Injury repair and fibrotic processes play an important role.
So far, still lack Effect study of the Tenascin-C in kidney trouble, the status based on the prior art, the application
Inventor it is quasi- attempt to find good Biological indicators object be applied to clinic, assist IgA nephrosis disease severity diagnosis and
Prognosis evaluation is provided in particular in urine Tenascin-C than creatinine (uTNC/Cr) and is used to prepare diagnosis and pre- as biomarker
The purposes in idiopathic IgA nephrosis preparation is assessed afterwards.
Summary of the invention
The object of the present invention is to provide the biomarker of a kind of new diagnosis and prognosis evaluation idiopathic IgA nephrosis, tools
Body is related to urine Tenascin-C and is used to prepare diagnosis and prognosis evaluation idiopathic IgA kidney as marker than creatinine (uTNC/Cr)
Purposes in sick preparation.Moreover, uTNC/Cr level can reflect glomerulus TNC expression quantity, reflect that the lesion of IgA nephrosis is serious
Degree assists the prognosis evaluation of IgA nephrosis indirectly.This application than the prior art detect time saving, sensitivity and accuracy it is higher, at
This is lower, and/or more efficient.
In addition, the present invention also provides the kits etc. applied for these.
It can be used as detection idiopathic IgA kidney than creatinine (uTNC/Cr) specifically, the present invention provides urine Tenascin-C
Sick biomarker.
Further, the present invention provides urine Tenascin-C is used to prepare diagnosis as marker than creatinine (uTNC/Cr)
With the purposes in prognosis evaluation idiopathic IgA nephrosis preparation.
The present invention by detection urine Tenascin-C than creatinine (uTNC/Cr), idiopathic IgA nephrotic as the result is shown
UTNC/Cr level is higher than normal person, and urinating TNC is not mainly to be generated by serum T NC through glomerular filtration, but by nephridial tissue
After the lesions expression such as middle segment hardening bead, crescent, it is excreted with urine；Meanwhile uTNC/Cr level can reflect glomerulus TNC
Expression quantity reflects the lesion severity of IgA nephrosis, can assist the prognosis evaluation of IgA nephrosis indirectly.
The uTNC/Cr level can reflect glomerulus TNC expression quantity, reflect the lesion severity of IgA nephrosis,
Connect assist IgA nephrosis prognosis evaluation, the present invention provides than the prior art detect time saving, sensitivity and accuracy it is higher, at
The preparation of this lower, and/or more efficient diagnosis and prognosis evaluation idiopathic IgA nephrosis or the kit applied for these.
Detailed description of the invention
Fig. 1 shows normal person, IgA nephrotic serum, the basic distribution situation for urinating Tenascin-C.
The correlation that Fig. 2 shows IgA nephrosis serum, urinates Tenascin-C.
Fig. 3 shows .IgA nephrotic nephridial tissue TNC wide expression in there are the cortex of lesion and damage, wherein being shown in
The positions such as glomerular mesangium area, segment hardening bead, global hardening, crescent, interstitial fibrosis, and in glomerulosclerosis portion
Expression is more in position, crescent.
Fig. 4 shows level of the urine Tenascin-C than creatinine (uTNC/Cr) in different glomerulonephritis.
Specific embodiment
1 normal person of embodiment, IgA nephrotic serum, the basic distribution situation experiment for urinating Tenascin-C
Using 6 normal human serum TNC 22.01 (16.83~38.61) ng/ml, urinate TNC/ creatinine 49.68 (40.65~
60.70)ug/g；And 134 idiopathic IgA nephrotic's serum T NC235.56 (165.21~295.90) ng/ml are used,
(54.32~250.02) ug/g of TNC/ creatinine 101.27 detection is urinated, the results show that IgA nephrotic serum, urine TNC are horizontal
Higher than normal person (as shown in Figure 1).
Embodiment 2IgA nephrosis serum, the correlation experimental study for urinating Tenascin-C
After related serum described in embodiment 1, urine TNC are carried out denary logarithm conversion, through Kolmogorov-
Smirnov examines the Normal Distribution Characteristics for meeting continuous variable, carries out to study population lg (sTNC), lg (uTNC/Cr)
Pearson correlation analysis calculates Pearson correlation coefficient r=0.03, P=0.729, i.e. IgA nephrotic serum, urine TNC
Being not significantly related to property of level (as shown in Figure 2)；Based on TNC polypeptide 220~330kDa of chain molecular weight, belong to high molecular weight protein, because
This, the results showed that urine TNC is not mainly to be generated by serum T NC through glomerular filtration, but by the lesion table of nephridial tissue itself
Up to generation, it is excreted with urine.
The correlation analysis of embodiment 3.IgA nephrosis serum, urine Tenascin-C and clinical indices is tested
Based on related serum described in embodiment 1, urine TNC, respectively to study population sTNC, uTNC/Cr and various clinics
Index carries out bivariate Spearman correlation analysis, calculates Spearman correlation coefficient r and conspicuousness P (as shown in table 1), knot
Fruit shows, sTNC and blood pressure, serum creatinine, eGFREPI, albumin, twenty-four-hour urine protein quantification, the reaction IgA nephrosis disease such as UACR
The clinical indices of severity being not significantly related to property；And Tenascin-C is urinated than creatinine (uTNC/Cr) and albumin, blood red egg
It is white that in significant negative correlation, (P < 0.001=is positively correlated with urine RBC, microdose urine protein/creatinine, can also from clinical indices
Speculate that urine Tenascin-C is more related with IgA nephrosis Renal tissues damage lesion than creatinine (uTNC/Cr).
1 serum of table, the correlation analysis for urinating Tenascin-C and clinical indices
The correlation analysis of embodiment 4.IgA nephrosis urine Tenascin-C and renal pathology morphological indexes
In view of the visible glomerulus Limited Number of renal needle biopsy tissue, the present embodiment is using the renal biopsy filtered out
It is sliced the case load n=112 of visible glomerulus number >=10, to the uTNC/Cr of above-mentioned 112 IgA nephrosis study population and each
Kind renal pathology morphological indexes carry out bivariate Spearman correlation analysis, calculate Spearman correlation coefficient r and show
Work property P, as the result is shown (as shown in table 2), as uTNC/Cr is increased, (crescent+segment hardening) percentage rises in conspicuousness
Trend (P=0.008).
Table 2 urinates correlation of the TNC than creatinine (uTNC/Cr) and Pathomorphology index
Successively filter out again renal biopsy be sliced visible glomerulus number >=15, >=20 case load be respectively n=75,
35, and carry out above-mentioned correlation analysis, the results show that (segment hardening+crescent) percentage, crescent percentage respectively with
UTNC/C conspicuousness is positively correlated, and conspicuousness P is respectively 0.042,0.023, and correlation coefficient r is respectively 0.236,0.384 (such as table 3
It is shown), the results showed that, urine Tenascin-C can reflect the hardening of nephridial tissue segment bead, crescent than creatinine (uTNC/Cr) level
The severity of the lesions such as body.
Table 3 urinates correlation of the TNC than creatinine (uTNC/Cr) and segment hardening bead, crescent
Embodiment 5.IgA nephrosis serum, the correlation analysis for urinating Tenascin-C and nephridial tissue Tenascin-C expression quantity
Tenascin-C (TNC) immunohistochemical staining, knot are carried out to above-mentioned 134 IgA nephrotic nephridial tissue paraffin piece
Fruit shows nephridial tissue TNC wide expression in there are the cortex of lesion and damage, such as glomerular mesangium area, segment to harden bead, the whole world
The positions such as hardening, crescent, interstitial fibrosis, and expressed more in glomerulosclerosis position, crescent；
Respectively to sTNC, uTNC/Cr and glomerulus, tubulo-interstital TNC expression scoring of 134 IgA nephrosis study populations
Bivariate Spearman correlation analysis is carried out, Spearman correlation coefficient r and conspicuousness P (as shown in table 4) is calculated, as a result shows
Show, serum T NC (sTNC) and glomerulus, tubulo-interstital TNC express being not significantly related to property；Urinate TNC/ creatinine (uTNC/Cr) and kidney
Bead, tubulo-interstital TNC expression scoring are positively correlated in significant, wherein expressing scoring Spearman correlation coefficient r with glomerulus TNC
=0.406, conspicuousness P < 0.001.
4 serum of table, the correlation for urinating Tenascin-C and nephridial tissue Tenascin-C expression quantity
The case load n=99 for filtering out visible glomerulus >=5 of immunohistochemistry piece comments glomerulus, tubulo-interstital TNC expression
Divide the Multiple linear regression analysis for being included in urine TNC/ creatinine (uTNC/Cr), " gradually " mode statistical is selected, the results show that " small
Pipe interstitial TNC expression scoring " is removed, and the linear of lg (uTNC/Cr) and glomerulus TNC the expression scoring (G-TNC) of fitting returns
Return equation:
Lg (uTNC/Cr) (ug/g)=1.735+0.1010* (G-TNC), regression coefficient R=0.394, P < 0.001 shows
Urine Tenascin-C can well reflect than creatinine (uTNC/Cr) level of glomerulus TNC expression quantity, reflection IgA nephrosis
Lesion severity has potential prognostic value.
Embodiment 6 urinates level of the Tenascin-C than creatinine (uTNC/Cr) in different glomerulonephritis
Continue detection and urinate level of the Tenascin-C than creatinine (uTNC/Cr) in different glomerulonephritis, as a result
It has been shown that, uTNC/Cr is in minute lesion (MCD), purpura nephritis (HSPN), ANCA related glomerulonephritis, focal segmental glomerulus
Normal group (as shown in Figure 4) is all remarkably higher than in ephritis (FSGS).
Claims (5)
1. urinating purposes of the Tenascin-C than creatinine in preparation diagnosis idiopathic IgA nephrosis preparation.
The purposes in prognosis evaluation idiopathic IgA nephrosis preparation is being prepared than creatinine 2. urinating Tenascin-C.
3. purposes as described in claim 1 or 2, which is characterized in that the urine Tenascin-C is than creatinine as marker.
4. purposes as described in claim 1 or 2, which is characterized in that the preparation compares flesh for detecting urine Tenascin-C
Its level in urine of acid anhydride.
5. purposes according to claim 4, which is characterized in that level of the urine Tenascin-C than creatinine in urine,
Reflect that bead, crescent lesion severity are hardened in segment in glomerulus TNC expression quantity and IgA nephrosis nephridial tissue.
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| CN112180093A (en) * | 2019-07-02 | 2021-01-05 | 复旦大学附属华山医院 | Critical disease mortality diagnostic biomarker tenascin-c and application thereof |
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| CN106177907A (en) * | 2015-04-30 | 2016-12-07 | 复旦大学附属华山医院 | Tenascin-C application in preparation diagnosis and treatment kidney injury preparation |
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| CN106177907A (en) * | 2015-04-30 | 2016-12-07 | 复旦大学附属华山医院 | Tenascin-C application in preparation diagnosis and treatment kidney injury preparation |
Non-Patent Citations (3)
| Title |
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| JAN HENRIK HORSTRUP ET AL: "Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease", 《NEPHROLOGY DIALYSIS TRANSPLANTATION》 * |
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| T MASAKI ET AL: "Role of Tenascin in Human Immunoglobulin A Nephropathy", 《THE JOURNAL OF INTERNATIONAL MEDICAL RESEARCH》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112180093A (en) * | 2019-07-02 | 2021-01-05 | 复旦大学附属华山医院 | Critical disease mortality diagnostic biomarker tenascin-c and application thereof |
| CN112180093B (en) * | 2019-07-02 | 2024-03-08 | 复旦大学附属华山医院 | Critical disease mortality diagnostic biomarker tenascin-c and application thereof |
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