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Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.

He X, Yin W, Ding Y, Cui SJ, Luan J, Zhao P, Yue X, Yu C, Laing X, Zhao Y - PLoS ONE (2015)

Bottom Line: A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA.More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV.This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

View Article: PubMed Central - PubMed

Affiliation: Clinical research center, Wuhan Children's Hospital, No. 100 Hongkong Rd,Wuhan, China.

ABSTRACT
IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

No MeSH data available.


Related in: MedlinePlus

The levels of serum AGT, C4A, SAA1, and KNG1 were measured by ELISA in IgAV, IgAVN and healthy controls (Con).Data represents the mean±SD. The expression levels were compared between different groups, IgAV(35), IgAVN (28), and Con(24) using t test.
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pone.0130536.g003: The levels of serum AGT, C4A, SAA1, and KNG1 were measured by ELISA in IgAV, IgAVN and healthy controls (Con).Data represents the mean±SD. The expression levels were compared between different groups, IgAV(35), IgAVN (28), and Con(24) using t test.

Mentions: In order to validate the results of proteomic analysis, we chose four proteins (SAA1, C4A, AGT, and KNG1) and measured their serum levels by using ELISA kits in the validation cohort, including 35 IgAV, 28 IgAVN, and 24 healthy controls. Consistent with the proteomic results, all four proteins were significantly high in IgAV and/or IgAVN patients (p<0.05). When comparing IgAV with IgAVN, IgAVN had prominently high AGT (p = 0.0005) but lower SAA1 and C4A (p = 0.031, p = 2.71E-5, respectively), and slightly lower KNG1 (p = 0.66) (Fig 3). SAA1 is an acute phase proteins, and it is not surprising that it was increased in patients with active IgAV. Moreover, we also investigated that SAA1 levels were positively correlated with C-reactive protein (CRP) [11], the most commonly used acute phase protein in clinical practice. C4A and KNG1 were not correlated with CRP, and the elevation in these serum proteins could not only due to systemic acute phase reaction but also contribute to the pathogenesis of IgAV. Among the four proteins, AGT is the only protein whose serum level was increased in IgAVN. AGT is the precursor of angiotensin I, which is further converted by ACE into angiotensin II, the key mediator of the renin-angiotensin system pathway. Therapy with ACE inhibitor has been shown to be beneficial in patients with IgAVN, and urine AGT levels were reported to be related to renal involvement of IgAV and may monitor the progression of IgAV. Thus, it is reasonable that serum AGT level is higher in IgAVN compared to that in IgAV in our study. It is worthy to further investigate the predictive role of serum AGT on the progression to IgAVN. For this propose, we collected samples during active phase from 102 patients with IgAV and followed up at least 6-months, among these patients, 16 missed follow-up, and 19 developed into IgAVN. After ELISA analysis, significantly higher AGT levels during active IgAV phase were found in patients who developed to IgAVN (19 cases) than patients who recovered (67 cases) (p<0.0001), and the AUC was 0.833 (95%CI: 0.74–0.93, p<0.001).


Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis.

He X, Yin W, Ding Y, Cui SJ, Luan J, Zhao P, Yue X, Yu C, Laing X, Zhao Y - PLoS ONE (2015)

The levels of serum AGT, C4A, SAA1, and KNG1 were measured by ELISA in IgAV, IgAVN and healthy controls (Con).Data represents the mean±SD. The expression levels were compared between different groups, IgAV(35), IgAVN (28), and Con(24) using t test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476708&req=5

pone.0130536.g003: The levels of serum AGT, C4A, SAA1, and KNG1 were measured by ELISA in IgAV, IgAVN and healthy controls (Con).Data represents the mean±SD. The expression levels were compared between different groups, IgAV(35), IgAVN (28), and Con(24) using t test.
Mentions: In order to validate the results of proteomic analysis, we chose four proteins (SAA1, C4A, AGT, and KNG1) and measured their serum levels by using ELISA kits in the validation cohort, including 35 IgAV, 28 IgAVN, and 24 healthy controls. Consistent with the proteomic results, all four proteins were significantly high in IgAV and/or IgAVN patients (p<0.05). When comparing IgAV with IgAVN, IgAVN had prominently high AGT (p = 0.0005) but lower SAA1 and C4A (p = 0.031, p = 2.71E-5, respectively), and slightly lower KNG1 (p = 0.66) (Fig 3). SAA1 is an acute phase proteins, and it is not surprising that it was increased in patients with active IgAV. Moreover, we also investigated that SAA1 levels were positively correlated with C-reactive protein (CRP) [11], the most commonly used acute phase protein in clinical practice. C4A and KNG1 were not correlated with CRP, and the elevation in these serum proteins could not only due to systemic acute phase reaction but also contribute to the pathogenesis of IgAV. Among the four proteins, AGT is the only protein whose serum level was increased in IgAVN. AGT is the precursor of angiotensin I, which is further converted by ACE into angiotensin II, the key mediator of the renin-angiotensin system pathway. Therapy with ACE inhibitor has been shown to be beneficial in patients with IgAVN, and urine AGT levels were reported to be related to renal involvement of IgAV and may monitor the progression of IgAV. Thus, it is reasonable that serum AGT level is higher in IgAVN compared to that in IgAV in our study. It is worthy to further investigate the predictive role of serum AGT on the progression to IgAVN. For this propose, we collected samples during active phase from 102 patients with IgAV and followed up at least 6-months, among these patients, 16 missed follow-up, and 19 developed into IgAVN. After ELISA analysis, significantly higher AGT levels during active IgAV phase were found in patients who developed to IgAVN (19 cases) than patients who recovered (67 cases) (p<0.0001), and the AUC was 0.833 (95%CI: 0.74–0.93, p<0.001).

Bottom Line: A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA.More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV.This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

View Article: PubMed Central - PubMed

Affiliation: Clinical research center, Wuhan Children's Hospital, No. 100 Hongkong Rd,Wuhan, China.

ABSTRACT
IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.

No MeSH data available.


Related in: MedlinePlus