The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte differentiation antigen BP-1/6C3 suggested that it is a member of the zincdependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [microsomal aminopeptidase; a-aminoacyl-peptide hydrolase (microsomal), EC 3. (refs. 4-6; unpublished results).While its broad tissue distribution implied diverse biological function, studies of the BP-1/6C3 antigen thus far have been focused mainly on its possible role in B lymphocyte development. The BP-1/6C3 molecule is expressed on pre-B and immature B-lineage cells in the bone marrow (2, 3, 7), and its expression on stromal cell lines correlates with their ability to support pre-B-cell growth (4). Moreover, interleukin 7 (IL-7) preferentially induces BP-1/6C3 expression together with pre-B-cell proliferation (6, 8) and up-regulated expression of the BP-1/6C3 antigen, which is often seen on transformed pre-B cells (1, 2, 9, 10).In an effort to define the structure and function of this interesting cell-surface molecule, we purified the antigen and cloned its cDNA from an Abelson murine leukemia virustransformed pre-B-cell line (11). The amino acid sequence predicted from the cDNA sequence suggested that the murine BP-1/6C3 antigen is a member of the zinc-dependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [APN; microsomal aminopeptidase; a-aminoacyl-peptide hydrolase (microsomal) EC 3.4.11.2]. Four distinctive types of aminopeptidases have been reported (12). These include APN, which has a relatively broad specificity acting on peptides with an N-terminal neutral amino acid; aminopeptidase A [APA; u-a-aspartyl(L-a-glutamyl)-peptide hydrolase, EC 3.4.11.7], acting on peptides with N-terminal acidic amino acids; aminopeptidase P (aminoacrylprolyl-peptide hydrolase, EC 3.4.11.9) and aminopeptidase W, which hydrolyze peptides in which the penultimate amino acid is a proline or a tryptophan.In the present studies, we have obtained evidence that the BP-1/6C3-reactive molecule exhibits APA activity.
Purpose
To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN).
Methods
Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD).
Results
Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters.
Conclusion
Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.
ABSTRACT. Current methods for diagnosing tuberculous pleurisy are poor. Some studies have explored the diagnostic value of a pleural effusion enzyme-linked immunospot (ELISPOT) assay, but its accuracy remains controversial. Therefore, we performed a meta-analysis of the existing evidence on the ability of the ELISPOT assay to diagnose tuberculous pleurisy. We systematically searched PubMed, Google Scholar, and EMBASE databases for studies measuring the sensitivity, specificity, and other measures of accuracy of the pleural effusion ELISPOT assay for diagnosis of tuberculous pleurisy. A total of nine studies were identified and subjected to meta-analysis, giving the following pooled values for sufficiently accurate to diagnose tuberculous pleurisy as a stand-alone technique. In fact, it appears to be superior to assays based on adenosine deaminase and gamma interferon for screening patients and confirming the diagnosis of tuberculous pleurisy.
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