Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autoimmune Response”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1987

Humoral response in Treponema pallidum-infected guinea pigs. II. Circulating immune complexes and autoimmune responses.

Guinea pigs of inbred strain 2 and of a strain deficient in complement component 4 (C4D) responded to intradermal infection with Treponema pallidum by production of antibodies to treponemal antigens, normal rabbit serum proteins, fibronectin, and creatine kinase and with formation of circulating immune complexes (IC). IC started to appear at low concentrations 1 mo after infection and increased between 3 and 5 mo post-infection. Antibodies to fibronectin appeared after the second month but were not detectable 30 days later. Antibody activity to creatine kinase was detectable at the fourth month and became significantly higher at 5 mo post-infection. Reinoculation with a dose similar to that used for primary infection caused a significant increase in all antibodies and IC. Dissociation products of IC formed after primary infection consisted predominantly of treponemal antibodies and antigens, whereas IC detected after reinfection consisted predominantly of antibodies and normal rabbit serum proteins. Antibodies to fibronectin and creatine kinase are considered autoantibodies, and the underlying mechanism responsible for their production in syphilis is discussed.

Animals↗
PubMed2001

Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid.

Bullous pemphigoid is an autoimmune blistering skin disease characterized by IgG autoantibodies targeting the skin basement membrane component type XVII collagen (BPAg2). To gain understanding of the disease's induction phase, we subcutaneously immunized adult BALB/c mice with peptides of human and/or the murine-equivalent BPAg2 pathogenic NC16A domain. Female mice were injected with peptides (human, murine, or combined human and murine), or PBS control emulsified in CFA, on a four-week interval. At the fourth and subsequent immunizations, all peptide-immunized mice were given murine peptides. Two weeks after the sixth immunization, ELISA detected IgG circulating autoantibodies against self peptides in 92% (47/51) of mice immunized with murine peptides; whereas none of the preimmune sera or the sera from PBS control-immunized mice reacted to the self peptides. In four mice their autoantibodies labeled mouse skin basement membrane. Breaking B-cell tolerance to BPAg2 sets the first step in dissecting the disease's induction phase.

Amino Acid Sequence↗
PubMed1986

Rabbit ocular and pineal autoimmune response to retina antigens.

Different forms of experimental autoimmune uveitis (EAU) can be produced by varying protocols to present different autoantigens to several species of experimental animal. We have studied the clinical, histological and serological responses of rabbits to footpad injection of various fractions of retina extract. Rabbits injected with retina extract or S antigen developed posterior uveitis. However, rabbits injected with retina extract, also developed an anterior uveitis and pinealitis not seen in rabbits receiving S antigen. The Serological response of rabbits to retina extract was different than that to purified S antigen. Antisera of rabbits receiving retina extract reacted with rabbit retina and pineal gland as well as with guinea pig retina but not with guinea pig pineal gland. In contrast anti-S antigen sera reacted with rabbit retina and guinea pig retina and pineal gland but not with rabbit pineal gland. Gel filtration chromatography of the ammonium sulfate supernate of retina extract was used to differentiate the antigens with which these two sera reacted. An analysis of these experiments gives preliminary evidence of an autoantigen(s) of rabbit retina and pineal gland that is not S antigen. The existence of multiple autoantigens common to retina and pineal gland in various species is significant in that it further underscores the relationship of these tissues. Furthermore, it is not unrealistic to expect more than one autoantigen of retina or uvea to be involved in autoimmune uveitis.

Animals↗
PubMed1986

Immunization of mice with purified U1 small nuclear ribonucleoprotein (RNP) induces a pattern of antibody specificities characteristic of the anti-Sm and anti-RNP autoimmune response of patients with lupus erythematosus, as measured by monoclonal antibodies.

Sera of patients with systemic lupus erythematosus and related autoimmune diseases often possess anti-Sm and anti-ribonucleoprotein (RNP) autoantibodies that recognize antigenic sites on small nuclear (sn) RNPs containing the snRNAs U1, U2, U4, U5, and U6. Although the major immunoreactive Sm polypeptides B', B, and D are present in snRNPs U1-U6, the RNP-antigenic proteins termed 70 kDa, A, and C are found only in U1 snRNP particles. We have immunized genetically nonautoimmune C57BL/6 mice with isolated human U1 snRNP particles and found that the major RNP and Sm antigenic polypeptides are also primarily immunogenic in the experimental immune response. Monoclonal antibodies (mAbs) derived from the mice thus immunized reacted specifically with polypeptides 70 kDa or A or recognized the Sm polypeptides B', B, and D simultaneously. One mAb reacted with an epitope shared by the U1 RNP polypeptide A and the U2 RNP polypeptide B". Competitive binding studies with the mAbs and anti-RNP/Sm patient sera indicated that the mAbs recognize the same regions on the antigenic snRNP polypeptides as the autoantibodies. This shows that B cells capable of producing autoantibodies against snRNPs are in principle present in the normal immune system. The striking similarity that we observed between the antibody pattern produced by the mice against exogenous U1 snRNP particles and that of systemic lupus erythematosus patients suggests the possibility that the anti-Sm and anti-RNP autoimmune response may be triggered by the endogenous U snRNPs rather than by a crossreacting viral or bacterial neoantigen. The possibility of eliciting anti-RNP and -Sm-type autoantibodies against exogenous snRNPs in normal mice should also allow potential pathogenic effects of such circulating antibodies to be investigated.

Animals↗
PubMed2006

Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses.

Multiple sclerosis (MS) is a disabling inflammatory, autoimmune demyelinating disease of the central nervous system. Despite intensive investigation, the mechanisms of disease pathogenesis remain unclear, and curative therapies are unavailable for MS. The current study describes a possible new strategy for the treatment of MS, based on the administration of the vasoactive intestinal peptide (VIP), a well-known immunosuppressive neuropeptide. Treatment with VIP significantly reduced incidence and severity of experimental autoimmune encephalomyelitis (EAE), in a MS-related rodent model system. VIP suppressed EAE neuropathology by reducing central nervous system inflammation, including the regulation of a wide spectrum of inflammatory mediators, and by selectively blocking encephalitogenic T-cell reactivity. Importantly, VIP treatment was therapeutically effective in established EAE and prevented the recurrence of the disease. Consequently, VIP represents a novel multistep therapeutic approach for the future treatment of human MS.

Animals↗
PubMed2000

Maturation of the humoral autoimmune response to epitopes of GAD in preclinical childhood type 1 diabetes.

GAD is a major target of autoimmunity in preclinical type 1 diabetes. Here we examine the maturation of the humoral response to GAD epitopes sequentially from birth to diabetes onset or current follow-up in 29 GAD antibody (GADA)+ offspring of parents with diabetes from the BABYDIAB Study. Antibodies were measured against GAD65, GAD67, and GAD65/67 chimeras by radiobinding assay. In 28 of 29 offspring, the first GADAs contained reactivity against epitopes within GAD65 residues 96-444, suggesting that the middle GAD65 region is a primary target of GAD humoral autoimmunity. In 7 of these 28 offspring, initial antibody reactivity was against all epitope regions tested (middle GAD65, COOH-terminal GAD65 residues 445-585, NH2-terminal GAD65 residues 1-95, and GAD67); in 16 offspring, reactivity was to middle and COOH-terminal GAD65 epitopes, and in 5 offspring, reactivity was only to the middle GAD65 epitopes. The single offspring without middle GAD65 reactivity had antibodies to the NH2-terminal epitopes in the absence of all other islet autoimmunity. Subsequent GADA epitope spreading was frequent and seen in 10 of 15 offspring with informative follow-up samples. Spreading was mostly (eight cases) to NH2-terminal GAD65 epitopes. In two offspring, spreading to new epitopes was found when antibody titers to GAD65 and early epitopes were declining, suggesting determinant-specific regulation of the humoral response. None of the GADA reactivities nor any changes in reactivity over time were specifically associated with diabetes onset. The findings suggest that the humoral autoimmune response to GAD found in childhood is dynamic, is initially against epitopes within the middle portion of GAD65, and spreads to epitopes in other regions of GAD65 and GAD67.

Antibody Formation↗
PubMed1999

Isoaspartyl post-translational modification triggers autoimmune responses to self-proteins.

The normal functioning immune system is programmed to attack foreign pathogens and other foreign proteins while maintaining tolerance to self-proteins. The mechanisms by which tolerance is broken in the initiation of autoimmunity are not completely understood. In the present study, mice immunized with the murine cytochrome c peptide 90-104 showed no response by the B or T cell compartments. However, immunization with the isoaspartyl form of this peptide, where the linkage of Asp(93) to Leu(94) occurs through the beta-carboxyl group, resulted in strong B and T cell autoimmune responses. Antibodies elicited by immunization with the isoaspartyl form of self-peptide were cross-reactive in binding to both isoforms of cytochrome c peptide and to native cytochrome c self-protein. In a similar manner, immunization of mice with the isoaspartyl form of a peptide autoantigen of human systemic lupus erythematosus (SLE) resulted in strong B and T cell responses while mice maintained tolerance to the normal aspartyl form of self-antigen. Isoaspartyl linkages within proteins are enhanced in aging and stressed cells and arise under physiological conditions. These post-translationally modified peptides may serve as an early immunologic stimulus in autoimmune disease.

Amino Acid Sequence↗
PubMed1990

Epitope patterns of anti-RNP antibodies in rheumatic diseases. Evidence for an antigen-driven autoimmune response.

Autoantibodies against small nuclear ribonucleoproteins (snRNP) are common in systemic lupus erythematosus and related disorders. The 3 categories, anti-(U1)RNP, anti-(U1, U2)RNP, and anti-Sm, all contain a common antibody specificity directed against the U1 snRNP-associated A protein. To determine the specificity of anti-U1 snRNP A protein antibodies for various antigenic sites, we tested 26 different anti-snRNP-positive sera for reactivity with fragments of the U1 snRNP A protein, which was produced using recombinant DNA technology. Several different fragments were shown to contain autoimmune-reactive epitopes, which indicates that the antibody response against the U1 snRNP A protein is polyclonal. Antibodies against a discontinuous or conformational epitope were found in most of the sera tested, regardless of whether they were classified as anti-(U1)RNP, anti-Sm, or anti-(U1, U2) RNP. These results strongly support the hypothesis that the anti-snRNP autoimmune response is antigen driven.

Antibodies, Antinuclear↗
PubMed1993

Humoral autoimmune response in Chagas' disease: Trypanosoma cruzi ribosomal antigens as immunizing agents.

Molecular expression cloning techniques have revealed that patients with chronic Chagas' heart disease (cChHD) present a strong humoral response against the cloned C-terminal portions of the four Trypanosoma cruzi ribosomal P proteins TcP1, TcP2 alpha (TcP2b), TcP2 beta (TcPJL5), and TcP0. This protein family presents several features that may be important in the immunopathology of Chagas disease. Their exposed location on the ribosome, and the amplification of their parasite-specific, Ser free C-terminal domain, generate a strong anti-parasite P response that may induce anti-P autoimmunity. Evidences indicate that the serological pattern of the anti-P response from chagasic patients may be the consequence of a chronic immunization with T. cruzi ribosomal antigens.

Amino Acid Sequence↗
PubMed1997

Time-dependent autoimmune response of dichloroacetyl chloride in female MRL +/+ mice.

Welders are exposed to dichloroacetyl chloride (DCAC) when trichloroethene (TCE) is used as a degreasing agent. Human exposure to TCE and tetrachloroethane can also lead to formation of DCAC in situ through metabolism. Due to its strong acylating property, it can bind with cellular macromolecules and act as hapten and consequently may elicit autoimmune (Al) response. Earlier, we reported that both TCE and DCAC induce/accelerate Al response in MRL +/+ mice, and DCAC even at 50 fold lower concentration induced greater Al responses. These studies, however, were conducted at a single time point (six weeks of treatment) and therefore necessitate a time-dependent characterization of this DCAC-induced Al response. Female MRL +/+ were given ip treatments of 0.2 mmol/kg DCAC in 100 microliters of corn oil every 4th day, while controls received an equal volume of corn oil only. DCAC treatment resulted in spleen weight increases at all time points whereas serum IgG showed significant increases at 4, 6 and 8 weeks of treatment. Serum autoantibodies, i.e., antinuclear antibodies, anti-single stranded DNA antibodies and anticardiolipin antibodies showed positive responses only after 4 weeks of treatment. However, the optimal responses were observed at 6 weeks and subsequently the responses diminished (at 8 weeks). The DCAC-specific antibodies showed a pattern similar to autoantibodies, i.e., an optimal response at 6 weeks of treatment. Our results thus suggest that DCAC under the current experimental conditions induces an optimal Al response at 6 weeks of treatment and further emphasize the usefulness of MRL +/+ mice in studying chemical-induced autoimmunity.

Acetates↗
PubMed2006

In the rat, citrullinated autologous fibrinogen is immunogenic but the induced autoimmune response is not arthritogenic.

Conversion of arginyl to citrullyl residues (citrullination) is essential for the formation of the epitopes recognized by rheumatoid arthritis (RA)-associated autoantibodies to citrullinated proteins (ACPA). ACPA are secreted by plasma cells of the rheumatoid synovial tissue where their major target, citrullinated fibrin, is abundant. Although numerous arguments suggest that ACPA play an important role in RA, their pathological relevance remains to be established. In the present study, we assessed the immunogenicity and arthritogenicity of complete Freund's adjuvant-emulsified autologous citrullinated (C-rFBG) or non-citrullinated (NC-rFBG) fibrinogen in Lewis (LEW) and Brown-Norway rats, which exhibit drastic differences in their susceptibility to induced autoimmune diseases. NC-rFBG induced no antibody response. In contrast, a single injection of C-rFBG induced an IgG response directed mainly to citrullinated determinants of rFBG. However, all rat strains remained devoid of clinical and histological signs of arthritis up to 3 months after C-rFBG inoculation. Next, in LEW rats, we tested whether autoimmunity to C-rFBG could aggravate acute ankle arthritis triggered by intra-articular injection of incomplete Freund's adjuvant (IFA). However, such arthritis evolved identically in the presence or absence of anti-C-rFBG autoantibodies. However, IFA-injected joints were devoid of citrullinated fibrin deposits. Therefore, citrullination allows breakdown of immunological tolerance but the autoimmune response developed is not spontaneously arthritogenic. Whether or not it can aggravate arthritis with citrullinated fibrin deposits remains to be evaluated.

Animals↗
PubMedDate not supplied

Isolated autoimmune response: definition, analysis of the prevalence in an outpatient rheumatology clinic, relationship to pre-clinical autoimmune disease and infections by hepatotropic viruses.

OBJECTIVE: To define the clinical significance of non-organ specific autoantibody positivity in patients in whom routine clinical and laboratory examinations did not detect any disease that might have caused the serological finding. METHODS: Out of 1,120 patients consecutively admitted to an outpatient rheumatology clinic, 28 were referred for the evaluation of an autoantibody positivity unrelated to the clinical status. These patients and 28 sex- and age-matched controls underwent a specific work-up with the aim of detecting any underlying infection or autoimmune disease. RESULTS: Eight of the 28 patients (28.5%) were found to be affected by a previously undetected disease: 3 chronic hepatitis C, 3 Sjögren's syndrome, and 2 autoimmune thyroiditis. The remaining 20 did not show any autoimmune or hepatic disease, although 4 of them showed active infection by HBV (n = 1) or HGV (n = 3) and 15 had had a previous infection by hepatotropic viruses (HBV, CMV or EBV). After a follow-up lasting 6-54 months, none of the last 20 patients developed any autoimmune or chronic hepatic disease. CONCLUSIONS: A diagnostic work-up is necessary in patients presenting with unexpected autoantibody positivity in order to detect an underlying pre-clinical autoimmune disease and/or unexpected hepatic infection. Patients in whom such a work-up fails to point out any condition should be further followed in order to make an early diagnosis of autoimmune disease.

Adolescent↗
PubMed1997

Diabetes results from a late change in the autoimmune response of NOD mice.

IDDM in the NOD mouse is the result of a chronic autoimmune process. NOD mice are shown to express benign autoimmunity that converts to a state of malignant autoimmunity and the development of IDDM. Young disease-prone NOD mice are in a state of benign autoimmunity that is correlated with a non-destructive response to islet tissue and the preservation of insulin-containing beta-cells. A proportion of mice with benign autoimmunity convert to having malignant autoimmunity. Clinical diabetes is diagnosed approximately 3 weeks from the development of malignant autoimmunity which is correlated with a destructive response to grafted islet tissue and extensive beta-cell destruction. We conclude that the development of clinical disease is correlated with a change in the state of autoimmunity, that is, from benign to malignant autoimmunity.

Animals↗
PubMed1993

Effect of gangliosides in the autoimmune response induced by liposome-associated antigens.

A model of autoimmunity to rat male accessory glands (RAG) was recently developed by intraperitoneal administration of three doses of native RAG associated with liposomes. In this work we analysed the effects of gangliosides in the cellular response to RAG when they were intraperitoneally administrated prior to the second dose of liposome-associated RAG. Results show that the ganglioside treatment could modify an established DTH response. Also, gangliosides markedly reduced the number of Ia antigen-positive peritoneal exudated cells (PEC). However, they modified neither the processing of liposomes through PEC nor their viability. Moreover, we obtained cellular response by transferring PEC from immunized donors into naive receptors.

Animals↗
PubMed1990

Humoral autoimmune response against S-antigen and IRBP in ocular onchocerciasis.

Autoimmune mechanisms are thought to play a role in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. In this study, the involvement of autoimmunity against retinal antigens in developing chorioretinitis was investigated. Serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid-binding protein (IRBP), were determined in patients with onchocerciasis (n = 46) and endemic controls (n = 38) from Sierra Leone with the use of an enzyme immunoassay. In both groups high levels of anti-human S-antigen and IRBP antibodies were detected. No relationship could be demonstrated between the antiretinal antibody level and the occurrence of chorioretinitis in onchocerciasis. The levels of both anti-human S-antigen and IRBP antibodies were significantly higher in patients with onchocerciasis compared with endemic controls (P less than 0.001). Cross-reactivity of antiretinal antibodies with parasitic antigens could not be demonstrated as a possible explanation for the higher levels in patients with onchocerciasis. No correlation was found between the levels of antibodies of different classes against the crude Onchocerca volvulus, the egg antigen, or the microfilariae and the antiretinal antibody levels. Furthermore, in a panel of 13 different monoclonal antibodies directed against O. volvulus, only one showed a slight anti-human IRBP reactivity and none reacted with S-antigen. The immune response against the two retinal antigens investigated was not specific for onchocerciasis because high antibody levels were also found in patients with Bancroftian filariasis from Papua, New Guinea, and Surinam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1962

Autoimmune response in rabbits injected with rat and rabbit liver ribosomes.

Autoimmune hemolytic anemia and leukopenia, circulating autoantibodies for erythrocytes, leukocytes, and ribosomes; pathological changes in liver, spleen, heart, brain, and kidneys were produced in rabbits injected with rat or rabbit liver ribosomes. The hematologic and pathologic changes were reproduced by injection of anti-ribosomal serum into normal rabbits. The autoantibody specificity was related primarily to nucleotides and nucleosides.

Animals↗