Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers of autoantibodies to HLA molecules and other surface markers of CD4+ T cells appear to increase with the progression of disease and may correlate with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the immune system. Genesis of autoreactivity may be related to structural homologies of HIV-1 env-products to such functional molecules involved in the control of self-tolerance. The most impressive similarities include the HLA-DR4 and DR2, the variable regions of TCR alpha-, beta-, and gamma-chain, the Fas protein, and several functional domains of IgG and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response, through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could also include the activation of membrane-to-nucleus signal transducers resulting in increased apoptosis. The evolution of autoimmune mechanisms during HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since aspects of oligoclonal immune response to HIV-1 components may occur in several autoimmune diseases which in some instances evolve to lymphoma.
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PMID:Autoreactivity in HIV-1 infection: the role of molecular mimicry. 776 37

Previous studies have demonstrated that T cell-reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR-N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.
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PMID:Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients. 897 84

Epstein-Barr virus has been implicated in the etiology of systemic lupus erythematosus (SLE) through serologic and immunologic studies. A potential mechanism for this influence is through molecular mimicry. The EBV nuclear antigen EBNA-1 contains a region, PPPGRRP, with considerable homology to the initial sequence targeted by antibodies in Sm B' autoimmunity, PPPGMRPP. This study examined whether immunization of rabbits and mice with peptides containing the PPPGRRP sequence from EBNA-1 constructed on a poly-lysine backbone was able to drive the development of autoantibodies against the Smith antigen (Sm) and the related antigenic complex, the U1 nuclear ribonucleoproteins (nRNPs). PPPGRRP immunization, and immunization with an EBNA-1 fragment containing PPPGRRP, led to autoantibodies in both rabbits and mice at high frequency (83% of rabbits and 43% of mice). Five out of six immunized rabbits developed either leucopenia or lymphopenia or both. The fine specificity of antibody binding against the lupus-associated autoantigens Sm B', nRNP A, and nRNP C after immunization with the EBNA-1-derived peptides was very similar to the early antibody binding patterns against these proteins in human SLE. This similarity, as well as the prevalence of autoimmunity after immunization with these peptides, identifies PPPGRRP as a strong candidate for molecular mimicry in SLE etiology.
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PMID:Lupus-like autoantibody development in rabbits and mice after immunization with EBNA-1 fragments. 1884 43

Systemic Lupus Erythematosus (SLE) is a disease of many faces and great mimicry. Women of child bearing ages are the potential candidates for this disease though it may occur in any age and sex group and the clinical manifestations do not vary with sex differentiation. Etiology of SLE is still to be defined and it has a prevalence of 27.7/100,000 population with higher rate of incidence in Asian and African women. This is a prospective study done from January, 2002 to December, 2006. The objective of the study was to observe the clinical profile and outcome of patients suffering from SLE. 33 patients were diagnosed following the ARA criteria. All the patients were investigated with ANA, anti ds-DNA antibody, routine blood and urine examination and follow up was done following SLE Disease Activity Index (SLEDAI) scoring system along with routine blood and urine examination. Mean age at presentation was 27.3 years with a standard deviation of 12.5. Among them, constitutional symptoms were present in 91% of the patients, hematological features were also present in 91% of patients where anemia was almost universal, one patient was suffering from autoimmune hemolytic anemia and 4 patients had thrombocytopenia. Mild leucopenia and lymphopenia was also observed in 33% patients. 60% patients show an ESR higher than 100 mm in 1st hour. Musculoskeletal and cutenous features were present in 81% and 75% cases respectively. 36% patients had some degree of renal involvement at the time of diagnosis. 6% patients had severe neuropsychiatric features. After appropriate management 52% patients leading a normal life with medication, 30% patients had a fluctuating course, 9% patients died and 9% lost follow up. Outcome was better in the patients who were diagnosed and treated early.
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PMID:Clinical profile, management and outcome of lupus. 1894 54