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  1. Article ; Online: Pemphigus vulgaris is characterized by low IgG reactivities to specific self-antigens along with high IgG reactivity to desmoglein 3.

    Fattal, Ittai / Rimer, Jacob / Shental, Noam / Molad, Yair / Gabrielli, Armando / Livneh, Avi / Sarig, Ofer / Goldberg, Ilan / Gafter, Uzi / Domany, Eytan / Cohen, Irun R

    Immunology

    2014  Volume 143, Issue 3, Page(s) 374–380

    Abstract: Pemphigus vulgaris (PV) is an autoimmune skin disease, which has been characterized by IgG autoantibodies to desmoglein 3. Here we studied the antibody signatures of PV patients compared with healthy subjects and with patients with two other autoimmune ... ...

    Abstract Pemphigus vulgaris (PV) is an autoimmune skin disease, which has been characterized by IgG autoantibodies to desmoglein 3. Here we studied the antibody signatures of PV patients compared with healthy subjects and with patients with two other autoimmune diseases with skin manifestations (systemic lupus erythematosus and scleroderma), using an antigen microarray and informatics analysis. We now report a previously unobserved phenomenon--patients with PV, compared with the healthy subjects and the two other diseases, show a significant decrease in IgG autoantibodies to a specific set of self-antigens. This novel finding demonstrates that an autoimmune disease may be associated with a loss of specific, healthy IgG autoantibodies and not only with a gain of specific, pathogenic IgG autoantibodies.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibody Specificity/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; Autoantigens/immunology ; Case-Control Studies ; Desmoglein 3/immunology ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Lupus Erythematosus, Systemic/immunology ; Male ; Middle Aged ; Pemphigus/immunology ; Scleroderma, Systemic/immunology
    Chemical Substances Autoantibodies ; Autoantigens ; Desmoglein 3 ; Immunoglobulin G
    Language English
    Publishing date 2014-05-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.12316
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ud II Zs.181: Show issues Location:
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  2. Article ; Online: Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome.

    Fattal, Ittai / Shental, Noam / Ben-Dor, Shifra / Molad, Yair / Gabrielli, Armando / Pokroy-Shapira, Elisheva / Oren, Shirly / Livneh, Avi / Langevitz, Pnina / Zandman-Goddard, Gisele / Sarig, Ofer / Margalit, Raanan / Gafter, Uzi / Domany, Eytan / Cohen, Irun R

    Immunology

    2015  Volume 146, Issue 3, Page(s) 401–410

    Abstract: In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus ... ...

    Abstract In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.
    MeSH term(s) Animals ; Antibodies, Antinuclear/blood ; Autoantibodies/blood ; Autoantigens/genetics ; Autoantigens/immunology ; Case-Control Studies ; CpG Islands ; Drosophila melanogaster/genetics ; Female ; Genome, Human ; Genome, Insect ; Humans ; Immunity, Innate ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NZB ; Pemphigus/genetics ; Pemphigus/immunology ; Poly G/genetics ; Poly G/immunology ; Poly T/genetics ; Poly T/immunology ; Scleroderma, Systemic/genetics ; Scleroderma, Systemic/immunology ; Species Specificity
    Chemical Substances Antibodies, Antinuclear ; Autoantibodies ; Autoantigens ; Immunoglobulin G ; Immunoglobulin M ; Poly T (25086-81-1) ; Poly G (25191-14-4)
    Language English
    Publishing date 2015-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.12514
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.181: Show issues Location:
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  3. Article ; Online: Epstein-Barr virus antibodies mark systemic lupus erythematosus and scleroderma patients negative for anti-DNA.

    Fattal, Ittai / Shental, Noam / Molad, Yair / Gabrielli, Armando / Pokroy-Shapira, Elisheva / Oren, Shirly / Livneh, Avi / Langevitz, Pnina / Pauzner, Rachel / Sarig, Ofer / Gafter, Uzi / Domany, Eytan / Cohen, Irun R

    Immunology

    2013  Volume 141, Issue 2, Page(s) 276–285

    Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities - anti-dsDNA is prominent. ... ...

    Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities - anti-dsDNA is prominent. Nevertheless, autoantibodies to dsDNA occur in only two-thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma (SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two-thirds of SLE patients reacted to a large spectrum of self-molecules that overlapped with their reactivity to dsDNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to dsDNA manifested abnormal antibody responses to Epstein-Barr virus (EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease.
    MeSH term(s) Antibodies, Antinuclear/blood ; Antibodies, Viral/blood ; Herpesvirus 4, Human/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Erythematosus, Systemic/immunology ; Scleroderma, Systemic/immunology
    Chemical Substances Antibodies, Antinuclear ; Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Language English
    Publishing date 2013-11-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.12200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins' diet.

    Ben-Ari, Ziv / Dalal, Adam / Morry, Ady / Pitlik, Silvio / Zinger, Pierre / Cohen, Jonathan / Fattal, Ittai / Galili-Mosberg, Ronit / Tessler, Debora / Baruch, Ruth Gershoni / Nuoffer, Jean-Marc / Largiader, Carlo R / Mandel, Hanna

    Journal of hepatology

    2010  Volume 52, Issue 2, Page(s) 292–295

    Abstract: Background & aims: Late-onset symptoms of urea-cycle disorder may lead to a life-threatening disease which is often undetected. We report the clinical and metabolic manifestations of acute hyperammonemic encephalopathy in a 47-year-old asymptomatic man ... ...

    Abstract Background & aims: Late-onset symptoms of urea-cycle disorder may lead to a life-threatening disease which is often undetected. We report the clinical and metabolic manifestations of acute hyperammonemic encephalopathy in a 47-year-old asymptomatic man with ornithine transcarbamylase (OTC) deficiency. The hyperammonemic encephalopathy was unmasked by a high-protein Atkins diet.
    Methods: Genetic analysis of the patient's family, 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects was performed using polymerase chain reaction amplification and DNA sequencing of the OTC gene.
    Results: Treatment with hemodialysis, provision of adequate calories to prevent catabolism, and protein elimination for 24h followed by protein restriction and ammonia scavenging medications effectively lowered the patient's plasma ammonia level and resulted in full recovery. Genetic analysis of the OTC gene revealed a novel hemizygous missense mutation in exon 5 (c.477T>G), leading to an isoleucine-to-methionine substitution in codon 159 (Ile159Met). Further genetic analysis of the patient's family yielded the mutation in many of them, although findings were negative in 89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects.
    Conclusions: This is the first reported case of an adult urea-cycle defect unmasked by the Atkins diet. Measurements of serum ammonia level must be part of the basic work-up in all patients presenting with encephalopathy of unknown origin even in the absence of liver dysfunction. Awareness of this important association can contribute to prompt diagnosis and life-saving treatment. Correct diagnosis is also important to prevent future recurrences and to provide genetic counselling for family members.
    MeSH term(s) Adult ; Age of Onset ; Amino Acid Substitution ; Brain Diseases, Metabolic/etiology ; Diet, Carbohydrate-Restricted/adverse effects ; Female ; Humans ; Hyperammonemia/etiology ; Jews/genetics ; Male ; Middle Aged ; Mutation, Missense ; Ornithine Carbamoyltransferase/genetics ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis ; Ornithine Carbamoyltransferase Deficiency Disease/enzymology ; Ornithine Carbamoyltransferase Deficiency Disease/genetics ; Pedigree
    Chemical Substances Ornithine Carbamoyltransferase (EC 2.1.3.3)
    Language English
    Publishing date 2010-02
    Publishing country Netherlands
    Document type Case Reports ; Journal Article
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2009.11.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: An antibody profile of systemic lupus erythematosus detected by antigen microarray

    Fattal, Ittai / Shental, Noam / Mevorach, Dror / Anaya, Juan-Manuel / Livneh, Avi / Langevitz, Pnina / Zandman-Goddard, Gisele / Pauzner, Rachel / Lerner, Miriam / Blank, Miri / Hincapie, Maria-Eugenia / Gafter, Uzi / Naparstek, Yaakov / Shoenfeld, Yehuda / Domany, Eytan / Cohen, Irun R

    Immunology. 2010 July, v. 130, no. 3

    2010  

    Abstract: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to ... ...

    Abstract Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states - SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.
    Keywords autoantibodies ; autoimmune diseases
    Language English
    Dates of publication 2010-07
    Size p. 337-343.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/j.1365-2567.2010.03245.x
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: An antibody profile of systemic lupus erythematosus detected by antigen microarray.

    Fattal, Ittai / Shental, Noam / Mevorach, Dror / Anaya, Juan-Manuel / Livneh, Avi / Langevitz, Pnina / Zandman-Goddard, Gisele / Pauzner, Rachel / Lerner, Miriam / Blank, Miri / Hincapie, Maria-Eugenia / Gafter, Uzi / Naparstek, Yaakov / Shoenfeld, Yehuda / Domany, Eytan / Cohen, Irun R

    Immunology

    2010  Volume 130, Issue 3, Page(s) 337–343

    Abstract: Summary: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim ... ...

    Abstract Summary: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states--SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.
    MeSH term(s) 12E7 Antigen ; Adult ; Antibodies, Anticardiolipin/immunology ; Antibodies, Antinuclear/blood ; Antibodies, Antinuclear/immunology ; Antigens, CD/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; Cell Adhesion Molecules/immunology ; Collagen Type III/immunology ; Down-Regulation/immunology ; Female ; Herpesvirus 4, Human/immunology ; Humans ; Hyaluronic Acid/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunoglobulin M/blood ; Immunoglobulin M/immunology ; Insulin-Like Growth Factor Binding Protein 1/immunology ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/immunology ; Lupus Nephritis/diagnosis ; Lupus Nephritis/immunology ; Male ; Middle Aged ; Peroxidase/immunology ; Protein Array Analysis ; Sensitivity and Specificity ; Up-Regulation/immunology
    Chemical Substances 12E7 Antigen ; Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Antigens, CD ; Autoantibodies ; CD99 protein, human ; Cell Adhesion Molecules ; Collagen Type III ; IGFBP1 protein, human ; Immunoglobulin G ; Immunoglobulin M ; Insulin-Like Growth Factor Binding Protein 1 ; Hyaluronic Acid (9004-61-9) ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2010-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/j.1365-2567.2010.03245.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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