Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With age, NZB mice develop anti-RBC autoantibodies resulting in the development of autoimmune hemolytic anemia. We now have evidence that this spontaneous autoantibody response consists of antibodies that are similar in specificity and Id expression to a pathogenic autoantibody (G8) that was cloned from an autoimmune NZB mouse. Similar to autoantibodies eluted from Coombs'-positive mouse E (MRBC), the G8 mAb recognizes native (unmodified) MRBC but not RBC from other species. Interestingly, G8 and four additional mAb bind with a higher titer to bromelain-treated MRBC than to native MRBC. Nucleotide sequence analysis reveals, however, that unlike "natural" antibodies that react solely with bromelain-MRBC, G8 is encoded by a J558 VH gene and a V kappa 12,13 L-chain gene. Thus G8 is clearly distinct from antibodies to bromelain-MRBC which are encoded by unrelated V genes. Instead, the sequence of the G8 VH chain was found to be nearly identical to that of an anti-DNA mAb derived from an MRL-lpr/lpr mouse. The results suggest Coombs'-positive autoantibodies from NZB mice are not derived from "natural" antibodies, but rather, consist of a restricted set of autoantibodies expressing the G8 IdX.
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PMID:A pathogenic monoclonal antibody, G8, is characteristic of antierythrocyte autoantibodies from Coombs'-positive NZB mice. 154 19

Both normal and autoimmune mice have IgM natural autoantibodies to bromelain-treated erythrocytes in which phosphatidylcholine (PTC) becomes exposed. At one stage this antibody may participate in the genesis of autoimmune hemolytic anemia in the NZB mouse. We have recently studied a patient with hemolytic anemia who had persistently high serum titers of IgM anticardiolipin antibodies (aCL) that were also demonstrated in a hemolysate of his erythrocytes obtained at the time of the anemia. We affinity-purified the antibody and sought its binding to normal human bromelain-treated erythrocytes (BrE) because of the IgM isotype of the antibody, since cardiolipin is not a constituent of the erythrocyte wall, and because the anionic phospholipids, with which aCL are known to cross-react, are not located at the outer leaflet of the erythrocyte membrane. We found binding of the antibody to HBrE in their hemolysates and by flow cytometry. We also demonstrated that the aCL cross-reacted extensively with PTC, as well as with other anionic or zwitterionic phospholipids. The purified IgM antibody lysed BrE in the presence of complement and also bound to in vitro-aged erythrocytes. Because this patient had no other evidence of systemic lupus erythematosus or any other autoimmune condition, his disease may represent a variant of the recently described primary antiphospholipid syndrome.
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PMID:Hemolytic anemia related to an IgM autoantibody to phosphatidylcholine that binds in vitro to stored and to bromelain-treated human erythrocytes. 208 93

New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain-treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation.
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PMID:Spontaneous production of anti-mouse red blood cell autoantibodies is independent of the polyclonal activation in NZB mice. 225 80

In 1990 our group reported a patient with autoimmune hemolytic anemia and high titers of IgM anticardiolipin antibodies that cross-reacted with phosphatidylcholine (PTC). These autoantibodies also recognized bromelain-treated erythrocytes (BrE) and in vitro aged erythrocytes. The epitope exposed with this treatment is PTC. To detect and characterize antiphosphatidylcholine antibodies (anti-PTC) in a normal human population, we studied by ELISA the presence of serum anti-PTC (IgG and IgM) in clinically healthy human subjects. The most representative samples were also studied for IgG or IgM activity against BrE by flow cytometry, rheumatoid factor activity, anti-dsDNA, anti-ssDNA by ELISA and by indirect immunofluorecence (IIF) using HEp-2 line and a healthy human fibroblast strain as substratum. Eighty five percent of sera had IgM anti-PTC and none had IgG. IgM antibodies against BrE were inhibited by PTC micelles (mPTC). Anti-PTC were also inhibited by phosphorylcholine and phosphatidic acid. Aggregated gammaglobulin (AGG) reactivity was inhibited by dsDNA and mPTC. The IgM anti-dsDNA activity was inhibited by soluble dsDNA, AGG and mPTC. All sera gave intermediate filaments pattern by IIF and reacted against purified vimentin by dot blot and Western blot.Our study shows hemolytic IgM anti-PTC present in normal human serum. The main epitope recognized by these autoantibodies is phosphorylcholine. The physicochemical characteristics, crossreactivity with self-antigens and functional properties are typical features of natural autoantibodies.
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PMID:Characterization of anti-phosphatidylcholine polyreactive natural autoantibodies from normal human subjects. 1190 50