Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0033687 (
proteinuria
)
24,015
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Preeclampsia is a placental disease characterized by hypertension and
proteinuria
in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C), endothelial activation (such as soluble endoglin and CD146), and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified
VSIG4
as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.
...
PMID:Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker. 2434 25
Background
C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G.
Methods
We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (
CRIg
-Fc) in the treatment of C3G.
CRIg
-Fc binds C3b and inhibits C3 and C5 convertases of the AP. Mice with mutations in the factor H and properdin genes (FH
m/m
P
-/-
) develop early-onset C3G, with AP consumption, high
proteinuria
, and lethal crescentic GN.
Results
Treatment of FH
m/m
P
-/-
mice with
CRIg
-Fc, but not a control IgG, inhibited AP activation and diminished the consumption of plasma C3, factor B, and C5.
CRIg
-Fc-treated FH
m/m
P
-/-
mice also had significantly improved survival and reduced
proteinuria
, hematuria, BUN, glomerular C3 fragment, C9 and fibrin deposition, and GN pathology scores.
Conclusions
Therapeutics developed on the basis of the mechanism of action of soluble
CRIg
may be effective for the treatment of C3G and should be explored clinically.
...
PMID:Prevention of Fatal C3 Glomerulopathy by Recombinant Complement Receptor of the Ig Superfamily. 2992 19
