Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small nuclear RNA molecules (snRNAs) are associated with polypeptides in vivo, forming small nuclear ribonucleoprotein complexes (snRNPs). These snRNP complexes are targets for certain autoimmune antisera. Antisera of the type anti-Sm precipitate (and therefore define) a class including U1, U2, U4, U5, and U6 snRNAs, whereas antisera of the anti-RNP type precipitate only U1 snRNPs. We used these two types of autoimmune antisera (from patients with systemic lupus erythematosus) to study the polypeptide components in human cells. Sequential immunoprecipitation of the complexes from nuclear extracts with anti-RNP and anti-Sm antibodies, along with radioimmunoassay of protein transfers, identified four polypeptides of 14,000 (P14), 17,000 (P17), 26,000 (P26), and 27,000 (P27) daltons that are present on all members of this class, whereas a 68,000-dalton (P68) polypeptide is present only on U1 snRNPs. Based on the radioimmunoassay, three of these polypeptides, P17, P26, and P27, are also the antigens for anti-Sm antisera, whereas P68 is the antigen for anti-RNP antisera. Long-term phosphate labeling experiments show that the only detectably phosphorylated polypeptide is P68, which contains phosphoserine.
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PMID:Polypeptide components of human small nuclear ribonucleoproteins. 622 17

The aims of this study were to investigate the influence of antiphospholipid antibodies (APA) on cumulative pregnancy and live-birth rates in patients undergoing assisted reproductive treatment. Serum samples from 173 patients were collected prior to initiation treatment cycle and tested by enzyme-linked immunosorbent assay (ELISA) for the presence of immunoglobulin (Ig)G, IgM and IgA against cardiolipin, phosphoserine, phosphoethanolamine, phosphoinositol, phosphatidic acid, and phosphoglycerol. Fifty-six samples from patients who had at least two failed cycles by assisted reproductive treatment were also tested by a bioassay for the presence of lupus anticoagulants. Both cumulative pregnancy and live birth rates were not affected by the presence of any specific or any number of seropositive APA. There was no association between multiple assisted reproductive treatment failures and APA seropositivity. Neither the serum concentration of any of the 18 APA, nor the number of positive APA was correlated with the number of assisted reproductive treatment failed cycles or affected the probability of pregnancy. No patient was found to be positive for lupus anticoagulants. Using life table analyses, which has been recognized as the most appropriate method available to analyse assisted reproductive treatment results, we conclude that there is no relationship between circulating APA and assisted reproductive treatment outcome. APA do not affect the early process of implantation or maintenance of pregnancy among assisted reproductive treatment patients.
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PMID:Cumulative pregnancy and live birth rates in women with antiphospholipid antibodies undergoing assisted reproduction. 1092 Jan 21

Using the recombinant La (SS-B) protein or a phosphorylated peptide derived thereof 27 La-specific human recombinant autoantibodies were selected from anti-La-positive systemic lupus erythematosus and systemic sclerosis patient-derived combinatorial phage display antibody libraries. Binding of these anti-La antibodies to various isoforms of the La protein present in normal and apoptotic cell extracts was analysed by Western blotting. Twenty-four of the selected antibodies recognize most, if not all isoforms of La, whereas three are exclusively reactive with the protein phosphorylated at serine-366. Sequence analysis of the selected antibodies showed a restricted spectrum of diversity in their VH germline gene usage. Remarkably, the recombinant antibodies recognizing exclusively the phosphoserine-366-containing isoform of La displayed a spleckled nucleoplasmic staining pattern in immunofluorescence analysis of HeLa and HEp-2 cells. This pattern differed markedly from those obtained with anti-La antibodies recognizing all isoforms of the La protein. Colocalization experiments with marker antibodies for spliceosomal UsnRNPs and RNA polymerase III subunits revealed that the anti-phosphorylated La antibodies stain the same nucleoplasmic speckles as anti-UsnRNP antibodies. In contrast to anti-UsnRNP antibodies the anti-phosphorylated La antibodies did not stain the Cajal bodies. In addition, no colocalization of phosphorylated La with RNA polymerase III was observed. Potential functional implications of the accumulation of phosphorylated La in nucleoplasmic speckles are discussed.
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PMID:Human recombinant anti-La (SS-B) autoantibodies demonstrate the accumulation of phosphoserine-366-containing la isoforms in nucleoplasmic speckles. 1269 Dec 62

Fmoc-O-benzyl-l-phosphoserine is an important building block in the synthesis of Forigerimod, a phosphopeptide being investigated for Systemic Lupus Erythematosus (SLE). An efficient one-pot process was developed using inexpensive, readily available starting materials. This general procedure was used to prepare a variety of protected phosphoamino acids.
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PMID:A general preparation of protected phosphoamino acids. 2235 80

The P140 peptide, a 21-mer linear peptide (sequence 131-151) generated from the spliceosomal SNRNP70/U1-70K protein, contains a phosphoserine residue at position 140. It significantly ameliorates clinical manifestations in autoimmune patients with systemic lupus erythematosus and enhances survival in MRL/lpr lupus-prone mice. Previous studies showed that after P140 treatment, there is an accumulation of autophagy markers sequestosome 1/p62 and MAP1LC3-II in MRL/lpr B cells, consistent with a downregulation of autophagic flux. We now identify chaperone-mediated autophagy (CMA) as a target of P140 and demonstrate that its inhibitory effect on CMA is likely tied to its ability to alter the composition of HSPA8/HSC70 heterocomplexes. As in the case of HSPA8, expression of the limiting CMA component LAMP2A, which is increased in MRL/lpr B cells, is downregulated after P140 treatment. We also show that P140, but not the unphosphorylated peptide, uses the clathrin-dependent endo-lysosomal pathway to enter into MRL/lpr B lymphocytes and accumulates in the lysosomal lumen where it may directly hamper lysosomal HSPA8 chaperoning functions, and also destabilize LAMP2A in lysosomes as a result of its effect on HSP90AA1. This dual effect may interfere with the endogenous autoantigen processing and loading to major histocompatibility complex class II molecules and as a consequence, lead to lower activation of autoreactive T cells. These results shed light on mechanisms by which P140 can modulate lupus disease and exert its tolerogenic activity in patients. The unique selective inhibitory effect of the P140 peptide on CMA may be harnessed in other pathological conditions in which reduction of CMA activity would be desired.
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PMID:Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide. 2571 62