Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the most distinguishing features of systemic lupus erythematosus is the presence of high concentrations of autoantibodies that recognize a limited number of self-antigens. Even though many lupus autoantigens have been identified, the inciting triggers of these abnormal immune responses are not fully understood. One mechanism that could generate these autoantibodies is a normal immune response toward a foreign epitope that mimics a common antigenic target of an autoantigen. Antibody generated toward the foreign epitope could also bind the autoantigen. This "cross-reactivity" would result in the presentation of the autoantigen to the immune system. Under autoimmune-prone conditions, tolerance toward the native protein is broken and an autoimmune response is initiated. Previously, it was suggested that Epstein-Barr virus might use such a mechanism to initiate an autoimmune response. Cross-reactive epitopes may have a similar amino acid sequence or a similar tertiary structure that is independent of amino acid sequence. A major, and likely initial, target of the lupus anti-SmB' response is a repeated, proline-rich sequence, PPPGMRPP. To identify potential cross-reactive targets, we used affinity-purified autoantibodies specific for PPPGMRPP to screen a random heptapeptide phage display library. Eighty-five clones were isolated and sequenced with eleven distinct sequence motifs being identified. Two of these motifs were homologous to the SmB' epitope, while the other nine were not. Interestingly, one of the peptide motifs that mimicked the SmB' epitope is identical to a peptide sequence found in the Epstein-Barr virus major DNA binding protein.
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PMID:Peptide mimics of a major lupus epitope of SmB/B'. 1272 42

The chromatin non-histone DNA binding protein high mobility group box one (HMGB1) has recently been extensively studied in autoimmune diseases. In addition to its nuclear functions, HMGB1 has been identified as alarmin that can 'alarm' both innate and adaptive immunity. HMGB1 can amplify inflammation and enhance immune responses by interacting with the receptor for Advanced Glycation End Products (RAGE) and Toll-like receptors 2,4 and 9 (TLRs) . Release of HMGB1 occurs during cell activation as well as cell death. Cells die by apoptosis and eventually necrosis which both are thought to lead to release of HMGB1 into the microenvironment. In the past years disturbed apoptosis or clearance of apoptotic cells has been put forward as a major pathophysiological feature in autoimmune diseases such as Systemic Lupus Erythematosus (SLE), which is a prototypic autoimmune disease that affects many organs. Accumulation of apoptotic cells has been found in SLE. Also, elevated levels of HMGB1 have been detected in the serum of SLE patients and increased expression of HMGB1 was demonstrated in skin lesions of lupus patients. In this review the general characteristics and activities of HMGB1 are highlighted and its role in SLE will be discussed with special attention to its involvement in the pathogenesis of skin lesions.
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PMID:HMGB1 in systemic lupus Erythematosus: Its role in cutaneous lesions development. 2054 55

The HERV-W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV-W-derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin-1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV-W members is highly desirable. A peptide nucleic acid (PNA)-mediated technique for the discrimination between multiple sclerosis-associated retrovirus and ERVWE1 sequence has been developed. The assay uses a PNA probe that, being fully complementary to the ERVWE1 but not to multiple sclerosis-associated retrovirus (MSRV) template, shows high selective potential. Single-stranded DNA binding protein facilitates the PNA-mediated, sequence-specific formation of strand invasion complex and, consequently, local DNA unwinding. The target DNA may be then excluded from further analysis in any downstream process such as single-stranded DNA-specific exonuclease action. Finally, the reaction conditions have been optimized, and several PNA probes that are targeted toward distinct loci along whole HERV-W env sequences have been evaluated. We believe that PNA/single-stranded DNA binding protein-based application has the potential to selectively discriminate particular HERV-W molecules as they are at least suspected to play pathogenic role in a broad range of medical conditions, from psycho-neurologic disorders (multiple sclerosis and schizophrenia) and cancers (breast cancer) to that of an auto-immunologic background (psoriasis and lupus erythematosus).
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PMID:The application of strand invasion phenomenon, directed by peptide nucleic acid (PNA) and single-stranded DNA binding protein (SSB) for the recognition of specific sequences of human endogenous retroviral HERV-W family. 2792 23