Human autoantibodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients

Pemphigus foliaceus (PF) patients have antibodies against a tightly, but noncovalently bound complex of polypeptides, which consists of desmoglein I (DGI) and other, possibly desmosomal, proteins. Most PF antibodies bind a calcium-sensitive epitope on this complex and chelation of calcium destroys the reactivity of these sera with the complex, but not the complex itself. The PF sera that do bind the desmosomal complex in the absence of calcium are those sera capable of binding denatured DGI on immunoblotting, and these same sera also immunoprecipitate only DGI when the desmosomal complex is dissociated with SDS. These findings demonstrate that autoantibodies against a complex of desmosome-associated proteins are characteristic of PF and define a calcium-sensitive conformational epitope on this complex.     

A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein

An antibody phage-display library was constructed from the B cells of convalescent severe acute respiratory syndrome (SARS) patients and screened using inactivated SARS coronavirus (CoV) virions as antigens. More than 80 positive clones were isolated from the library and one of them, scFv H12, was extensively characterized. scFv H12 bound to SARS-CoV with high affinity (equilibrium dissociation constant, Kd=73.5 nM), and neutralized SARS virions in vitro. The facts that scFv H12 bound to the SARS-S1 protein under non-reducing conditions and that it did not bind to monomeric S1 protein under reducing conditions strongly suggest that scFv H12 recognizes a conformational epitope shared by oligomeric S1 proteins. This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine.     

A student-developed tool for assessing safety in schizophrenic patients

Schizophrenia is a chronic, disabling disease of mind and behavior. Since some schizophrenics are prone to violence, nursing students devised a safety risk assessment tool to help health care personnel screen clients in acute care settings who may be at risk for violent behavior. The tool is accurate, quick, and user-friendly, and it enhances communication among members of the multidisciplinary health care team. The results obtained from the assessment tool guide nurses and other health care team members in implementing appropriate interventions. Future research and pilot studies are warranted to increase the reliability and validity of this tool.     

Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas'' disease patients

Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.     

57例精神分裂症患者康复治疗效果分析

目的促进社区精神残疾工作规范化 ,科学地评估各种康复措施及社会心理因素对精神病患者预后的影响。方法对研究社区采用整群抽样 ,建立精神病家庭社会康复机构 ,街道居委会建立监护小组或指定监护人 ,精神科医生对患者进行维持治疗和康复评估。结果实施社区康复措施后 ,精神分裂症患者均能坚持药物维持治疗 ,社会功能评价与康复效果较为满意。结论社区康复治疗可提高精神分裂症患者的治疗依从性 ,减少复发。     

Streptokinase binds to lactate dehydrogenase subunit-M, which shares an epitope with plasminogen

The bacterial thrombolytic agent streptokinase binds to human, porcine, and chicken lactate dehydrogenase (EC 1.1.1.27; LD) isoenzyme subunit M, but not to the H or C subunits. There is amino acid sequence homology between LD and the streptokinase binding site on plasminogen to account for this interaction that results in the formation of high-molecular-mass complexes in serum that contain LD activity. Binding of highly immunogenic streptokinase with LD may lead to induction of anti-LD autoantibodies, known to occur in some patients after therapeutic administration of streptokinase for treatment of acute myocardial infarction. This interaction may also be a general mechanism for inducing autoimmunity against other proteins that share the streptokinase binding epitope.     

Natural anti-A and anti-B of the ABO system: allo- and autoantibodies have different epitope specificity

BACKGROUND: According to Landsteiner's law, alloantibodies are prevalent and autoantibodies are absent in the ABO blood group system. However, one study (Spalter et al., Blood 1999;93:4418‐24) has suggested that low‐affinity ABO autoantibodies, mitigated by anti‐idiotypic immunoglobulins are also prevalent, while another publication (Rieben et al., Eur J Immunol 1992;22:2713‐7) shows that humans do not have B‐lymphocytes capable of producing immunoglobulin G ABO autoantibodies. STUDY DESIGN AND METHODS: We used hapten‐specific chromatography to isolate allo‐ and autoantibodies from pools of A or B serum and then characterized the resultant antibodies against a wide range of ABO and related glycoconjugates. RESULTS: We found that the apparent autoantibodies are directed against blood group A or B disaccharides, without consideration for the presence of fucose, but requiring the absence of elongating sugar X in composition of Gal(NAc)α1‐3(Fucα1‐2)Galβ1‐X–terminated carbohydrate chain. In contrast, ABO alloantibodies required a minimum trisaccharide Gal(NAc)α1‐3(Fucα1‐2)Gal epitope and recognize the elongated type‐specific tetrasaccharides. Furthermore, alloantibodies appear to be a small set of specific yet crossreactive antibodies that detect all backbone types of A or B antigens, rather than being a collection of specific antibodies, each of which detects a different type of A or B antigen. CONCLUSION: Apparent ABO autoantibodies appear to have no natural human target.