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Peptide Antibodies (peptide + antibody)
Selected AbstractsCitrullinated peptide and its relevance to rheumatoid arthritis: an updateINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2010Stanislav LUBAN Abstract Citrullinated peptides in autoimmune diseases have been extensively studied in the last two decades. It is suggested that citrullination and the anti-citrullinated peptide antibodies (ACPA) plays a critical role in initiating inflammatory responses in autoimmune diseases, such as rheumatoid arthritis (RA). The most commonly accepted molecular mechanism for citrullinated peptides/proteins in RA is that the modified antigen resulting from cell damage or uncontrolled apoptosis could evoke an immune response leading to autoantibodies against these peptide or the whole protein. Citrullination of arginine is catalyzed by the enzyme peptidylarginine-deiminase (PAD) in the presence of calcium, changing the positively charged arginine to a polar but neutral citrulline. These citrullinated peptides/proteins and the relevant antibodies (ACPA) are important, not only in initiation of RA, but also in the diagnosis of the disease. In this evidence-based clinical review, we summarize recently published data on peptide citrullination and ACPA gauging the ability of anti-cyclic citrullinated peptide (anti-CCP) antibodies for diagnosis of RA. We also recapitulate results of studies elucidating the mechanism underlying the disease. [source] Detection of the Sm31 antigen in sera of Schistosoma mansoni, infected patients from a low endemic areaPARASITE IMMUNOLOGY, Issue 1 2010G. S. SULBARÁN Summary Schistosoma mansoni cathepsin B (Sm31) is a major antigen from adult worms that circulates in the blood of infected patients (Li et al., Parasitol Res 1996; 82: 14,18). An analysis of the Sm31 sequence (Klinkert et al., Mol Biochem Parasitol 1989; 33: 113,122) allowed the prediction of seven hydrophilic regions that were confirmed to be exposed on the surface of a 3D model of Sm31; the species specificity of these regions was checked using BLAST analysis. The corresponding peptides were chemically synthesized in polymerazible forms using the t-Boc technique. Rabbits developed a high humoral response against these peptides as tested by a multiple antigen blot assay; it recognized native Sm31 in crude S. mansoni extracts and as circulating antigen in sera of S. mansoni-infected patients by western blot. Relevant antigenic determinants were located at the N- and C-terminus sequences. Antibodies against these regions recognized the native enzyme in an ELISA-like assay called cysteine protease immuno assay in which the immunocaptured enzyme was revealed by the intrinsic cathepsin B hydrolytic activity of Sm31. The method successfully and specifically detected Sm31 in sera of infected individuals, most of them (83·3%) with light infections, offering a rationale for the development of parasite enzyme capture assays using anti-synthetic peptide antibodies for possible use in the diagnosis of schistoso,iasis. [source] Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serumPROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2009H. Ulrich Scherer Abstract In several autoimmune disorders, including rheumatoid arthritis (RA), autoantibodies are thought to be the driving force of pathogenicity. Glycosylation of the Fc-part of human Igs is known to modulate biological activity. Hitherto, glycosylation of human IgG-Fc has been analyzed predominantly at the level of total serum IgG, revealing reduced galactosylation in RA. Given the pathogenic relevance of autoantibodies in RA, we wished, in the present study, to address the question whether distinct Fc-glycosylation features are observable at the level of antigen-specific IgG subpopulations. For this purpose, we have developed a method for the microscale purification and Fc-glycosylation analysis of anti-citrullinated peptide antibodies (ACPA). ACPA represent a group of autoantibodies that occur with unique specificity in RA patients. Their presence is associated with increased inflammatory disease activity and rapid joint destruction. Results indicate that ACPA of the IgG1 subclass vary considerably from total serum IgG1 with respect to Fc-galactosylation, with galactosylation being higher on ACPA than on serum IgG1 for some patients, while other patients show higher galactosylation on serum IgG1 than on ACPA. Using this method, studies can be performed on the biological and clinical relevance of ACPA glycosylation within RA patient cohorts. [source] Anti,cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathwaysARTHRITIS & RHEUMATISM, Issue 7 2009L. A. Trouw Objective It has been suggested that anti,citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti,cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. Methods We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide,coated plates, specific buffers, and normal and complement-deficient sera as a source of complement. Results Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti-CCP antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place. Conclusion Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA. [source] Different roles for anti,cyclic citrullinated peptide antibodies and CD4+CD28null cells in the acceleration of atherosclerosis in rheumatoid arthritis: Comment on the article by Farragher et alARTHRITIS & RHEUMATISM, Issue 2 2009Roberto Gerli MD No abstract is available for this article. [source] Patients with pulmonary tuberculosis are frequently positive for anti,cyclic citrullinated peptide antibodies, but their sera also react with unmodified arginine-containing peptideARTHRITIS & RHEUMATISM, Issue 6 2008Prasanthi Kakumanu Objective The anti,cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) has high sensitivity and specificity for rheumatoid arthritis (RA). However, detection of anti-CCP in patients with active pulmonary tuberculosis (TB) has recently been reported. To determine whether this activity was specific for the citrullinated residue, the specificity of anti-CCP,positive sera for CCP versus that for unmodified arginine-containing peptide (CAP) was examined in patients with TB and compared with that in patients with RA. Methods Anti-CCP and anti-CAP in sera from patients with pulmonary TB (n = 49), RA patients (n = 36), and controls (n = 18) were tested by ELISA. Sera were available at diagnosis from most TB patients. All TB patients were treated with a combination of 2,4 antibiotics for at least 6 months, and sera were collected over time. Results Anti-CCP was found in 37% of TB patients and in 43% of RA patients. CAP reactivity was more common in TB than in RA. High anti-CCP:anti-CAP ratios (>2.0) were seen far more commonly in anti-CCP,positive RA patients than in anti-CCP,positive TB patients (94% versus 22%). Anti-CCP was inhibited by CCP peptide in sera from RA patients, but not in sera from TB patients. A slight increase in anti-CCP was common after initiating treatment for TB, although the anti-CCP level decreased after 1,2 months. Conclusion Anti-CCP is frequently present in patients with active TB. However, many anti-CCP,positive TB sera also reacted with CAP, and anti-CCP:anti-CAP ratios in TB sera were low. Anti-CCP:anti-CAP ratios should be useful clinically for distinguishing CCP-specific reactivity seen in RA from reactivity with both CCP and CAP frequently seen in pulmonary TB. [source] Anti,cyclic citrullinated peptide antibodies in psoriasis patients without arthritisARTHRITIS & RHEUMATISM, Issue 5 2006Raik Böckelmann MD No abstract is available for this article. [source] Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti,citrullinated protein antibodies in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 3 2006Federico Pratesi Objective To test the hypothesis that deimination of viral sequences containing Arg,Gly repeats could generate epitopes recognized by anti,citrullinated protein antibodies (ACPAs) that are present in rheumatoid arthritis (RA) sera. Methods Multiple antigen peptides derived from Epstein-Barr virus (EBV),encoded Epstein-Barr nuclear antigen 1 (EBNA-1) were synthesized, substituting the arginines with citrulline, and were used to screen RA sera. Anti,cyclic citrullinated peptide antibodies were purified by affinity chromatography and tested on a panel of in vitro deiminated proteins. Their ability to bind in vivo deiminated proteins was evaluated by immunoprecipitation, using EBV-infected cell lines. Results Antibodies specific for a peptide corresponding to the EBNA-135,58 sequence containing citrulline in place of arginine (viral citrullinated peptide [VCP]) were detected in 50% of RA sera and in <5% of normal and disease control sera. In addition, affinity-purified anti-VCP antibodies from RA sera reacted with filaggrin-derived citrullinated peptides, with deiminated fibrinogen, and with deiminated recombinant EBNA-1. Moreover, anti-VCP antibodies immunoprecipitated, from the lysate of calcium ionophore,stimulated lymphoblastoid cell lines, an 80-kd band that was reactive with a monoclonal anti,EBNA-1 antibody and with anti,modified citrulline antibodies. Conclusion These data indicate that ACPAs react with a viral deiminated protein and suggest that EBV infection may play a role in the induction of these RA-specific antibodies. [source] Topology and patch-clamp analysis of the sodium channel in relationship to the anti-lipid a antibody in campylobacteriosisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2008Seigo Usuki Abstract An infecting strain VLA2/18 of Campylobacter jejuni was obtained from an individual with campylobacteriosis and used to prepare chicken sera by experimental infection to investigate the role of serum anti-ganglioside antibodies in Guillain-Barré syndrome. Both sera of the patient and chicken contained anti-ganglioside antibodies and anti-Lipid A (anti-Kdo2-Lipid A) antibodies directed against the lipid A portion of the bacterial lipooligosaccharide. The anti-Kdo2-Lipid A activities inhibited voltage-gated Na (Nav) channel of NSC-34 cells in culture. We hypothesized that anti-Kdo2-Lipid A antibody acts on the functional inhibition of Nav1.4. To test this possibility, a rabbit peptide antibody (anti-Nav1.4 pAb) against a 19-mer peptide (KELKDNHILNHVGLTDGPR) on the , subunit of Nav1.4 was produced. Anti-Nav1.4 pAb was cross-reactive to Kdo2-Lipid A. Anti-Kdo2-lipid A antibody activity in the chicken serum was tested for the Na+ current inhibition in NSC-34 cells in combination with ,-Conotoxin and tetrodotoxin. Contrary to our expectations, the anti-Kdo2-Lipid A antibody activity was extended to Nav channels other than Nav1.4. By overlapping structural analysis, it was found that there might be multiple peptide epitopes containing certain dipeptides showing a structural similarity with v-Lipid A. Thus, our study suggests the possibility that there are multiple epitopic peptides on the extracellular domains of Nav1.1 to 1.9, and some of them may represent target sites for anti-Kdo2-Lipid A antibody, to induce neurophysiological changes in GBS by disrupting the normal function of the Nav channels. © 2008 Wiley-Liss, Inc. [source] Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010N. R. LEWIS Summary Background, Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity. Aim, To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies. Methods, Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease. Results, Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6,89.9) and 93.0% (95% CI, 91.2,94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5,95.5) and 96.5% (95% CI, 95.2,97.5) respectively. Conclusion, Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease. [source] ACVIM Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment, and PreventionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2006Meryl P. Littman The purpose of this report is to offer a consensus opinion of ACVIM diplomates on the diagnosis, treatment, and prevention of Borrelia burgdorferi infections in dogs (canine Lyme disease). Clinical syndromes known to commonly be associated with canine Lyme disease include polyarthritis and glomerulopathy. Serological test results can be used to document exposure to B. burgdorferi but not prove illness. Although serum enzyme-linked immunosorbent assay/indirect fluorescent antibody assay titers can stay positive for months to years after treatment, quantitative C6 peptide antibody paired tests need more study. Serological screening of healthy dogs is controversial because it can lead to overdiagnosis or overtreatment of normal dogs, most of which never develop Lyme disease. However, serological screening can provide seroprevalence and sentinel data and stimulate owner education about tick infections and control. Although it is unknown whether treatment of seropositive healthy dogs is beneficial, the consensus is that seropositive dogs should be evaluated for proteinuria and other coinfections and tick control prescribed. Tick control can include a product that repels or protects against tick attachment, thereby helping to prevent transmission of coinfections as well as Borrelia spp. Seropositive dogs with clinical abnormalities thought to arise from Lyme disease generally are treated with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer treatment as well as medications and diets for protein-losing nephropathy. The ACVIM diplomates believe the use of Lyme vaccines still is controversial and most do not administer them. It is the consensus opinion that additional research is needed to study predictors of illness, "Lyme nephropathy," and coinfections in Lyme endemic areas. [source] Experimental model of IgA nephropathy using KM mouse (second report): Possible protective effect of anti-IgA1 synthetic hinge peptide antibody on glomerular deposition of underglycosylated IgA1NEPHROLOGY, Issue 2006YOSHIYUKI HIKI [source] A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 10 2010Wenfeng Tan Objective We previously observed the association of the co-occurrence of the HLA,DRB1 shared epitope (SE) and RANKL single-nucleotide polymorphisms (SNPs) with younger age at the onset of rheumatoid arthritis (RA) in 182 rheumatoid factor (RF),positive European American patients with early-onset RA. The aim of this study was to fine-map the 48-kb RANKL region in the extended cohort of 210 European American RF-positive patients with early RA, to seek replication of RA-associated SNPs in additional RA cohorts of 501 European Americans and 298 African Americans, and to explore the functional consequences of RA-associated SNPs. Methods SNP genotyping was conducted using pyrosequencing or TaqMan polymerase chain reaction (PCR) assays. Associations of rs7984870 with RANKL expression in plasma, peripheral blood mononuclear cells, and isolated T cells were quantified using enzyme-linked immunosorbent assay and reverse transcription,PCR. Site-directed mutagenesis of rs7984870 within the 2-kb RANKL promoter was performed to drive the luciferase reporter gene in osteoblast and stromal cell lines. Interaction of DNA and protein was determined by electrophoretic mobility shift assay. Results A single promoter SNP, rs7984870, was consistently significantly associated with earlier age at the onset of RA in 3 independent seropositive (RF or anti,cyclic citrullinated peptide antibody) RA cohorts but not in seronegative RA patients. The C risk allele of rs7984870 conferred 2-fold higher plasma RANKL levels in RF-positive patients with RA, significantly elevated RANKL messenger RNA expression in activated normal T cells, and increased promoter activity after stimulation in vitro via differential binding to the transcription factor SOX5. Conclusion The RANKL promoter allele that increased transcription levels upon stimulation might promote interaction between activated T cells and dendritic cells, predisposing to a younger age at the onset of RA in seropositive European American and African American patients. [source] Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2010Heidi Kokkonen Objective To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA). Methods A nested case,control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system. Results The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1, [IL-1,], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-,, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow,derived factors (IL-7, granulocyte,macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1,). The levels were particularly increased in anti,cyclic citrullinated peptide antibody, and rheumatoid factor,positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell,related cytokines, while chemokines, stromal cell,derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA. Conclusion Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell,related factors); after disease onset, the involvement and activation of the immune system was more general and widespread. [source] Anti-cyclic citrullinated peptide antibody (anti-CCP antibody) is present in the sera of patients with dementia of Alzheimer's type in AsianACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010K. Satoh Satoh K, Kawakami A, Shirabe S, Tamai M, Sato A, Tsujihata M, Nagasato K, Eguchi K. Anti-cyclic citrullinated peptide antibody (anti-CCP antibody) is present in the sera of patients with dementia of Alzheimer's type in Asian. Acta Neurol Scand. 2010: 121: 338,341. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background,,, In the hippocampi of Alzheimer's disease (AD) patients, aberrant expression of citrullinated proteins and peptidylarginase 2 (PADI2) has been identified. We explored the functional roles of these proteins by means of detection of serum anti-cyclic citrullinated peptide antibody (anti-CCP antibody) in patients with dementia of Alzheimer's type (DAT). Methods,,, Sera were obtained from 42 patients with DAT, 30 patients with other neurological disorders and 42 healthy controls. Gender ratio and age were comparable among the three groups. The level of anti-CCP antibody in sera was examined by ELISA. Findings,,, Anti-CCP antibody was not found in the 30 patients with other neurological disorders, and only one of the 42 healthy controls (2.4%) was positive. However, surprisingly, anti-CCP antibody was clearly detected in eight of the 42 DAT patients. Interpretation,,, Anti-CCP antibody appears to be a simple and early serologic biomarker for DAT among dementia patients. Additionally, our data imply that citrullinated proteins accumulated in the astrocytes of AD patients acquire neo-antigenicity, inducing anti-CCP antibody production. [source] Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010N. R. LEWIS Summary Background, Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity. Aim, To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies. Methods, Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease. Results, Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6,89.9) and 93.0% (95% CI, 91.2,94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5,95.5) and 96.5% (95% CI, 95.2,97.5) respectively. Conclusion, Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease. [source] | |||||||||||||