Home About us Contact
|
Home About us Contact | ||
|
|
||
Autoantibody Specificities (autoantibody + specificity)
Selected AbstractsClose temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodiesARTHRITIS & RHEUMATISM, Issue 9 2010Ami A. Shah Objective This study was undertaken to examine the temporal relationship between scleroderma development and malignancy, and to evaluate whether this differs by autoantibody status among affected patients. Methods Study participants had a diagnosis of scleroderma, a diagnosis of cancer, cancer, an available serum sample, and a cancer pathology specimen. Sera were tested for autoantibodies against topoisomerase I, centromere, and RNA polymerase I/III by immunoprecipitation and/or enzyme-linked immunosorbent assay. Clinical and demographic characteristics were compared across autoantibody categories. Expression of RNA polymerases I and III was evaluated by immunohistochemistry using cancerous tissue from patients with anti,RNA polymerase antibodies. Results Twenty-three patients were enrolled. Six patients tested positive for anti,RNA polymerase I/III, 5 for anti,topoisomerase I, and 8 for anticentromere, and 4 were not positive for any of these antigens. The median duration of scleroderma at cancer diagnosis differed significantly between groups (,1.2 years in the anti,RNA polymerase I/III group, +13.4 years in the anti,topoisomerase I group, +11.1 years in the anticentromere group, and +2.3 years in the group that was negative for all antigens tested) (P = 0.027). RNA polymerase III demonstrated a robust nucleolar staining pattern in 4 of 5 available tumors from patients with antibodies to RNA polymerase I/III. In contrast, nucleolar RNA polymerase III staining was not detected in any of 4 examined tumors from the RNA polymerase antibody,negative group (P = 0.048). Conclusion Our findings indicate that there is a close temporal relationship between the onset of cancer and scleroderma in patients with antibodies to RNA polymerase I/III, which is distinct from scleroderma patients with other autoantibody specificities. In this study, autoantibody response and tumor antigen expression are associated. We propose that malignancy may initiate the scleroderma-specific immune response and drive disease in a subset of scleroderma patients. [source] Analysis of the autoimmune epitopes on human testicular NASP using recombinant and synthetic peptidesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2000I. N. Batova The human nuclear autoantigenic sperm protein, NASP, is a testicular histone-binding protein of 787 amino acids to which most vasectomized men develop autoantibodies. In this study to define the boundaries of antigenic regions and epitope recognition pattern, recombinant deletion mutants spanning the entire protein coding sequence and a human NASP cDNA sublibrary were screened with vasectomy patients' sera. Employing panel sera from 21 vasectomy patients with anti-sperm antibodies, a heterogeneous pattern of autoantibody binding to the recombinant polypeptides was detected in ELISA and immunoblotting. The majority of sera (20/21) had antibodies to one or more of the NASP fusion proteins. Antigenic sites preferentially recognized by the individual patients' sera were located within aa 32,352 and aa 572,787. Using a patient's serum selected for its reactivity to the whole recombinant protein in Western blots, cDNA clones positive for the C-terminal domain of the molecule were identified. The number and location of linear epitopes in this region were determined by synthetic peptide mapping and inhibition studies. The epitope-containing segment was delimited to the sequence aa 619,692 and analysis of a series of 74 concurrent overlapping 9mer synthetic peptides encompassing this region revealed four linear epitopes: amino acid residues IREKIEDAK (aa 648,656), KESQRSGNV (aa 656,664), AELALKATL (aa 665,673) and GFTPGGGGS (aa 680,688). All individual patients' sera reacted with epitopes within the sequence IRE,.GGS (aa 648,688). The strongest reactivity was displayed by peptides corresponding to the sequence AELALKATL (aa 665,673). Thus, multiple continuous autoimmune epitopes in NASP involving sequences in the conserved C-terminal domain as well as in the less conserved testis-specific N-terminal region comprising the histone-binding sites, as predicted for an antigen-driven immune response, may be a target of autoantibodies in vasectomized men and may provide a relevant laboratory variable to describe more accurately the spectrum of autoantibody specificities associated with the clinical manifestation of vasectomy. [source] Methods to detect antifibrillarin antibodies in patients with systemic sclerosis (SSc): A comparisonJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2004Josefina Huerta García Abstract Autoantibodies against nucleolar antigens are common in systemic sclerosis (SSc). They include autoantibodies against fibrillarin (Fb), which are serological markers for SSc. Fb is associated with the evolutionally-conserved box C/D of small nucleolar RNAs (snoRNAs). We compared indirect immunofluorescence (IIF), Western blot (WB), and immunoprecipitation (IPP) of total small RNAs assays to determine which of these techniques is most specific for the detection of snoRNPs. We also examined the frequency and specificity of autoantibodies from SSc patients to snoRNAs, snRNAs, and scRNAs, and concluded that 1) IIF can not determine autoantibody specificity against Fb, 2) 36% of SSc sera were false-negative by WB, and 3) by IPP, anti-Fb autoantibodies from SSc patients can bind U3, U8, U13, U15, and U22 snoRNAs. J. Clin. Lab. Anal. 18:19,26, 2004. © 2004 Wiley-Liss, Inc. [source] A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathyARTHRITIS & RHEUMATISM, Issue 9 2010Lisa Christopher-Stine Objective Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune-mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, and the question of which patients would benefit from immunosuppression remains unanswered. The aim of this study was to identify novel autoantibodies in patients with necrotizing myopathy. Methods Muscle biopsy specimens and serum samples were available for 225 patients with myopathy. Antibody specificities were determined by performing immunoprecipitations from 35S-methionine,labeled HeLa cell lysates. Selected biopsy specimens were stained for membrane attack complex, class I major histocompatibility complex (MHC), and endothelial cell marker CD31. Results Muscle biopsy specimens from 38 of 225 patients showed predominantly myofiber necrosis. Twelve of these patients had a known autoantibody association with or other etiology for their myopathy. Sixteen of the remaining 26 sera immunoprecipitated 200-kd and 100-kd proteins; this specificity was observed in only 1 of 187 patients without necrotizing myopathy. Patients with the anti-200/100 autoantibody specificity had proximal weakness (100%), high creatine kinase levels (mean maximum 10,333 IU/liter), and an irritable myopathy on electromyography (88%). Sixty-three percent of these patients had been exposed to statins prior to the onset of weakness. All patients responded to immunosuppressive therapy, and many experienced a relapse of weakness when the medication was tapered. Immunohistochemical studies showed membrane attack complex on small blood vessels in 6 of 8 patients and on the surface of non-necrotic myofibers in 4 of 8 patients. Five of 8 patients had abnormal capillary morphology, and 4 of 8 patients expressed class I MHC on the surface of non-necrotic myofibers. Conclusion An anti,200/100-kd specificity defines a subgroup of patients with necrotizing myopathy who previously were considered to be autoantibody negative. We propose that these patients have an immune-mediated myopathy that is frequently associated with prior statin use and should be treated with immunosuppressive therapy. [source] | ||||||||||