Nitration of H2B histone elicits an immune response in experimental animals.


:Histone H2B is an autoantigen that appears in circulation due to altered apoptosis/or insufficient clearance and is likely to be involved in the induction and progression of autoimmune diseases since modified-H2B is immunogenic. Our studies demonstrate that tyrosines of H2B histone spontaneously converts to free and nitrotyrosine bound protein in vivo. Commercially available H2B histone was modified with peroxynitrite in vitro. Modified H2B was found to be more immunogenic than native form in experimental animals. Furthermore, the sera of rabbits were analyzed for the native and modified forms of the H2B histone. The binding specificity of autoantibodies was characterized by competitive enzyme-linked immunosorbent assay (ELISA) and band shift assay. The free 3-nitrotyrosine in systemic lupus erythematosus sera was quantified by high-performance liquid chromatography. Peroxynitrite-modified H2B induced high titre antibodies as compared to native form which were directly proportional to the nitrotyrosine content. Furthermore, the induced antibodies showed specificity towards the immunogen and cross-reacted with tyrosine-nitrated proteins. ELISA showed preferential binding of induced anti-peroxynitrite modified H2B antibodies to modified H2B as compared to native H2B. The present study shows that peroxynitrite modification of self-antigen(s) generates neoepitopes capable of inducing modified-H2B autoantibodies in experimental animals.






Khan MA,Alam K,Hassan SM,Rizvi MMA




Has Abstract


2017-06-01 00:00:00












  • Lack of 64,000-M(r) islet autoantigen overexpression and antibody development following coxsackievirus B4 infection in diabetes-resistant mice.

    abstract::Congenic B10.BR/SgSnJ H-2kTlaa mice were infected with a diabetogenic strain of coxsackievirus CB4 to correlate abnormalities of sugar metabolism with virus replication in islets, 64,000-M(r) (64K) islet autoantigen expression, 64K antibody development, and pancreas histopathology in early and late infection. Plaque a...


    pub_type: 杂志文章


    authors: Gerling I,Chatterjee NK

    更新日期:1993-01-01 00:00:00

  • HLA-DP-positive T cells in patients with systemic lupus erythematosus.

    abstract::HLA-DP+ T cells in peripheral blood from 23 patients with systemic lupus erythematosus (SLE) were examined using two-colour flow cytometry analysis. A marked increase of HLA-DP+ T cells was observed in patients with SLE (20.5-98.7%; 59.8 +/- 20.8%) in comparison to normal subjects (1.3-20.6%; 11.1 +/- 7.2%), and the r...


    pub_type: 杂志文章


    authors: Tokano Y,Hishikawa T,Hirose T,Sekigawa I,Hashimoto H,Okumura K,Hirose S

    更新日期:1990-01-01 00:00:00

  • Polyarthritis in MRL-lpr/lpr mice: mouse type II collagen is antigenic but not arthritogenic.

    abstract::In addition to a lupus-like syndrome and massive T cell proliferation, MRL-lpr/lpr(MRL/l) mice develop an arthritic process very similar serologically and histologically to human rheumatoid arthritis (RA). Recently, we have developed in DBA/1 mice an experimental model of autoimmune arthritis (EAA) which shares clinic...


    pub_type: 杂志文章


    authors: Boissier MC,Texier B,Carlioz A,Fournier C

    更新日期:1989-01-01 00:00:00

  • Oral tolerisation to pyruvate dehydrogenase complex as a potential therapy for primary biliary cirrhosis.

    abstract::Primary biliary cirrhosis (PBC) is characterised by immune-mediated damage to the intra-hepatic biliary epithelial cells (BEC). Immuno-modulatory/suppressive therapy represents, therefore, alogical approach to treatment in this disease. Conventional immuno-suppressive and immuno-modulatory agents suffer from the bread...


    pub_type: 杂志文章


    authors: Jones DE,Palmer JM,Robe A,Kirby JA

    更新日期:2002-12-01 00:00:00

  • Autoimmunity in vitiligo: relationship with HLA, Gm and Km polymorphisms.

    abstract::Eighty-six patients affected by vitiligo were investigated for Gm, and Km polymorphisms, HLA markers and the presence of organ and non organ-specific autoantibodies. Vitiligo patients had an increased frequency of autoantibodies (71%), in particular anti-parietal cells (26.6%), antithyroglobulin (24.4%) and antithyroi...


    pub_type: 杂志文章


    authors: Lorini R,Orecchia G,Martinetti M,Dugoujon JM,Cuccia M

    更新日期:1992-01-01 00:00:00

  • Induction of a multiple sclerosis-like disease in mice with an immunodominant epitope of myelin oligodendrocyte glycoprotein.

    abstract::Myelin oligodendrocyte glycoprotein (MOG) is postulated to be a target autoantigen in multiple sclerosis (MS). Here we investigated the encephalitogenicity of an immunodominant epitope of MOG, peptide 35-55, in various strains of mice. An MS-like disease was induced in NOD/Lt mice (H-2g7) and C57BL/6 mice (H-2b) by a ...


    pub_type: 杂志文章


    authors: Slavin A,Ewing C,Liu J,Ichikawa M,Slavin J,Bernard CC

    更新日期:1998-01-01 00:00:00

  • CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice.

    abstract::NZW "x" BXSB F1 mice develop SLE that is associated with an anti-phospholipid syndrome characterized by anti-cardiolipin antibodies, thrombocytopenia and small coronary artery thrombosis. This syndrome is immune mediated and, dependent, on CD4+T cells. To determine whether disease in these mice can be treated with blo...


    pub_type: 杂志文章


    authors: Akkerman A,Huang W,Wang X,Ramanujam M,Schiffer L,Madaio M,Factor SM,Davidson A

    更新日期:2004-09-01 00:00:00

  • Anti-carbonic anhydrase II antibodies in systemic sclerosis: association with lung involvement.

    abstract::Carbonic anhydrase II (CAII) is expressed on alveolar epithelium and participates to CO2 elimination, fluid secretion and post-capillary pH regulation. CAII is overexpressed in animal models of lung fibrosis in sites of epithelial injury. Autoantibodies directed against CAII (anti-CAII) have been described in sera fro...


    pub_type: 杂志文章


    authors: Alessandri C,Bombardieri M,Scrivo R,Viganego F,Conti F,de Luca N,Riccieri V,Valesini G

    更新日期:2003-03-01 00:00:00

  • Immunosuppressive therapies in myasthenia gravis.

    abstract::Immunosuppression is the mainstay of treatment for myasthenia gravis (MG). In this paper, we review the mechanisms of action and clinical application of corticosteroids and different classes of immunosuppressive drugs that are currently used in MG patients, and present the results of their use in more than 1000 patien...


    pub_type: 杂志文章,评审


    authors: Sanders DB,Evoli A

    更新日期:2010-08-01 00:00:00

  • Distinct role of T helper Type 17 immune response for Graves' hyperthyroidism in mice with different genetic backgrounds.

    abstract::T helper type 17 (Th17) cells, a newly identified effector T-cell subset, have recently been shown to play a role in numerous autoimmune diseases, including iodine-induced autoimmune thyroiditis in non-obese diabetic (NOD)-H2(h4) mice, which had previously been thought Th1-dominant. We here studied the role of Th17 in...


    pub_type: 杂志文章


    authors: Horie I,Abiru N,Saitoh O,Ichikawa T,Iwakura Y,Eguchi K,Nagayama Y

    更新日期:2011-03-01 00:00:00

  • Apoptotic cells selectively suppress the Th1 cytokine interferon gamma in stimulated human peripheral blood mononuclear cells and shift the Th1/Th2 balance towards Th2.

    abstract::Apoptotic cells are readily recognized and engulfed by phagocytes and usually do not induce inflammation or tissue damage. Furthermore, they can actively suppress a pro-inflammatory response in phagocytes: In the presence of apoptotic cells, activated monocytes/macrophages produce more of the anti-inflammatory and imm...


    pub_type: 杂志文章


    authors: Girkontaite I,Urbonaviciute V,Maseda D,Neubert K,Herrmann M,Voll RE

    更新日期:2007-06-01 00:00:00

  • Elevated levels of anti-Helicobacter pylori antibodies in Henoch-Schönlein purpura.

    abstract:OBJECTIVE:Henoch-Schonlein purpura (HSP) is a systemic vasculitis characterized by IgA-containing deposits in the skin, joints, gastrointestinal mucosa and glomeruli. HSP is much rarer in adults than in children. Among a number of other pathogenic factors, Helicobacter pylori (Hp) has recently been implicated in the ga...


    pub_type: 杂志文章


    authors: Novák J,Szekanecz Z,Sebesi J,Takáts A,Demeter P,Bene L,Sipka S,Csiki Z

    更新日期:2003-08-01 00:00:00

  • CTLs' repertoire shaping in the thymus: a Monte Carlo simulation.

    abstract:MOTIVATION:The human immune system evolved a multi-layered control mechanism to eliminate self-reactive cells. Of these so-called tolerance induction mechanisms, lymphocytes T education in the thymus gland represents the very first one. This complicated process is not fully understood and quantitative models able to he...


    pub_type: 杂志文章


    authors: Castiglione F,Santoni D,Rapin N

    更新日期:2011-06-01 00:00:00

  • Systematic simulation of cross-reactivity predicts ambiguity in Tk memory: it may save lives of the infected, but limits specificities vital for further responses.

    abstract::The present study uses the agent-based model IMMSIM to simulate immune responses to a viral infection, with a focus on the impact of preformed memory (homologous and heterologous) on the quality and the efficacy of the response. The in machina results confirm the observed thwarting of new, naïve responses exerted by c...


    pub_type: 杂志文章


    authors: Pearson YE,Cheng Y,Selin LK,Puzone R,Celada F

    更新日期:2011-06-01 00:00:00

  • A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE.

    abstract::In a previous study, we showed that the Ly6G(-)CD11b(+) blood monocytes residing in naïve mice are intrinsically immunosuppressive and that loss of this suppressive function may contribute to the development of autoimmunity in experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis....


    pub_type: 杂志文章


    authors: Slaney CY,Toker A,Fraser JD,Harper JL,Bäckström BT

    更新日期:2013-06-01 00:00:00

  • Effect of mycobacterial infection in the lupus-prone MRL/lpr mice: enhancement of life span of autoimmune mice, amelioration of kidney disease and transient decrease in host resistance.

    abstract::We have used the MRL/lpr murine model of spontaneous lupus to investigate three questions in infection immunity: (1) does mycobacterial infection have any effect on the mortality of the autoimmunity-prone lpr mice?; (2) does the infection modify the progression of kidney disease of lpr lupus?; and (3) does the lpr gen...


    pub_type: 杂志文章


    authors: Castro AP,Esaguy N,Aguas AP

    更新日期:1993-01-01 00:00:00

  • Complement regulatory proteins and autoimmunity.

    abstract::The complement system is known to be involved in autoimmunity at several levels. Activated complement contributes to the inflammatory tissue injury characteristic of many autoimmune disease settings. On the other hand, early components of the classical pathway, including C1q, C4 and C2, are thought to be important for...


    pub_type: 杂志文章,评审


    authors: Song WC

    更新日期:2006-08-01 00:00:00

  • The infectious etiology of vasculitis.

    abstract::Infectious agents have been implicated in the etiopathogenesis of various vasculitides via numerous and overlapping mechanisms including direct microbial invasion of endothelial cells, immune complex mediated vessel wall damage and stimulation of autoreactive B and/or T cells through molecular mimicry and superantigen...


    pub_type: 杂志文章,评审


    authors: Lidar M,Lipschitz N,Langevitz P,Shoenfeld Y

    更新日期:2009-08-01 00:00:00

  • PD-1/PD-L pathway and autoimmunity.

    abstract::Programmed cell death 1 (PD-1) was isolated in 1992 by subtractive-hybridization technique, as a molecule whose expression is enhanced by apoptotic stimuli. Since then we have been analyzing the function of PD-1 in the regulation of immune responses. Generation of PD-1 deficient mice, pathophysiological analyses of au...


    pub_type: 杂志文章,评审


    authors: Okazaki T,Wang J

    更新日期:2005-08-01 00:00:00

  • Costimulatory molecules and autoimmune thyroid diseases.

    abstract::At least two signals for proliferation and cytokine secretion by T-cells are required. The first signal is delivered through the interaction of the T-cell receptor with major histocompatibility complex (MHC) molecules expressed on the surface of antigen-presenting cells (APC). The second or costimulatory signal is del...


    pub_type: 杂志文章,评审


    authors: Salmaso C,Olive D,Pesce G,Bagnasco M

    更新日期:2002-05-01 00:00:00

  • High circulating IL-6 level in Graves' ophthalmopathy.

    abstract::IL-6 is a paracrine and autocrine cytokine, which acts in the regulation of immunological and inflammatory processes. Its production can be observed in different cell types, as well as thyrocytes. The purpose of the study was to examine the serum IL-6 levels between the patients with Graves' disease (N = 47) and witho...


    pub_type: 杂志文章


    authors: Molnár I,Balázs C

    更新日期:1997-01-01 00:00:00

  • T cells infiltrating the skin of Tsk2 scleroderma-like mice exhibit T cell receptor bias.

    abstract::The T cell repertoire expressed by Tsk2 mice, a novel experimental model of systemic sclerosis, was examined to determine whether cells infiltrating the areas of involved skin exhibit a T cell receptor (TCR) bias. Reverse transcription-polymerase chain reactions (RT-PCR) were conducted using RNA extracted from lymph n...


    pub_type: 杂志文章


    authors: Wooley PH,Sud S,Langendorfer A,Calkins C,Christner PJ,Peters J,Jimenez SA

    更新日期:1998-01-01 00:00:00

  • Distinct surface phenotypes of B cells responsible for spontaneous production of IgM and IgG anti-DNA antibodies in autoimmune-prone NZB x NZW F1 mice.

    abstract::Autoimmune-prone NZB x NZW F1 (B/W F1) mice produce a high titer of anti-DNA antibodies, In vivo and in vitro studies showed that in the early life of these mice, the immunoglobulin isotype of these antibodies almost exclusively belongs to IgM class, however, IgG anti-DNA antibodies begin to develop when the mice are ...


    pub_type: 杂志文章


    authors: Okada T,Abe M,Takiura F,Hirose S,Shirai T

    更新日期:1990-01-01 00:00:00

  • The clinical characteristics of autoimmune haemolytic anaemia/Evans syndrome patients with clonal immunoglobulin/T cell receptor gene rearrangement.

    abstract:OBJECTIVE:To investigate the clinical features of AIHA/ES patients with clonal Ig/TCR gene rearrangement. METHODS:Ig/TCR gene rearrangements were measured by BIOMED-2 PCR. 44 primary AIHA/ES patients were enrolled in the study. Clinical characteristics were analyzed and compared between patients with and without clona...


    pub_type: 杂志文章


    authors: Zhu H,Zhao M,Cao Z,Yang J,Li Y,Xing L

    更新日期:2020-11-01 00:00:00

  • Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients.

    abstract:OBJECTIVE:The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. MATERIAL AND METHODS:Peripheral blood from 40 healthy donors (HD) and 66 MS patients [...


    pub_type: 杂志文章


    authors: Teniente-Serra A,Grau-López L,Mansilla MJ,Fernández-Sanmartín M,Ester Condins A,Ramo-Tello C,Martínez-Cáceres E

    更新日期:2016-06-01 00:00:00

  • Thymosin and the spontaneously diabetic BB rat.

    abstract::The biological basis for autoimmunity and immunoincompetence in the BB rat has yet to be localized. In spite of normal thymic histology, thymocyte subsets and blastogenesis, thymus gland products (thymosins) have yet to be studied. In the present report, thymus gland function was studied by measuring thymosin alpha 1 ...


    pub_type: 杂志文章


    authors: Winter WE,Robbins V,Elder M,Barrett D,Martin N,Maclaren NK

    更新日期:1988-01-01 00:00:00

  • Inflammatory arthritis and systemic bone loss are attenuated by gastrointestinal helminth parasites.

    abstract::Infections with different helminth species have been observed to ameliorate a variety of chronic inflammatory diseases. Herein, we show that the natural murine helminth species, Heligmosomoides polygyrus bakeri (Hp) is capable of attenuating disease severity in two different inflammatory arthritis models. Furthermore,...


    pub_type: 杂志文章


    authors: Sarter K,Kulagin M,Schett G,Harris NL,Zaiss MM

    更新日期:2017-05-01 00:00:00

  • Inhibition of autoimmune disease by the immunomodulator linomide correlates with the ability to activate macrophages.

    abstract::Linomide is a potent immunomodulator that has been shown to inhibit autoimmunity in several animal models of autoimmune disease, including experimental autoimmune encephalomyelitis (EAE). Linomide's mechanism of action is unknown, however, it has been suggested to modulate the function of antigen presenting cells (APC...


    pub_type: 杂志文章


    authors: Dahlén E,Andersson M,Dawe K,Tellander AC,Brunmark C,Björk A,Hedlund G

    更新日期:2000-10-01 00:00:00

  • Both early and late apoptotic blebs are taken up by DC and induce IL-6 production.

    abstract::During apo blebs, containing nuclear components, are formed at the cells' surfaces. When these blebs separate from the dying cell an apo cell body remains. The contents of apo blebs are modified and can be released, especially in patients with systemic lupus erythematosus (SLE) since impaired clearance of apo material...


    pub_type: 杂志文章


    authors: Fransen JH,Hilbrands LB,Jacobs CW,Adema GJ,Berden JH,Van der Vlag J

    更新日期:2009-05-01 00:00:00

  • A study of conformational restraints on reactivity of human PR3-specific autoantibodies (ANCA) facilitated through protein folding manipulations of a new recombinant proteinase 3 protein.

    abstract::Proteinase 3 (PR3)-specific antineutrophil cytoplasmic autoantibodies (PR3-ANCA) recognize conformational epitopes on PR3. This study evaluates PR3-ANCA target epitopes utilizing a novel recombinant PR3 (rPR3) produced to accommodate manipulations of the N-terminal domain. The rPR3 molecule contains an N-terminus six ...


    pub_type: 杂志文章


    authors: Farrag L,Pendergraft WF 3rd,Yang JJ,Jennette JC,Falk RJ,Preston GA

    更新日期:2007-11-01 00:00:00