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IgG Autoantibodies (igg + autoantibody)
Selected AbstractsPeripheral B cell receptor editing may promote the production of high-affinity autoantibodies in CD22-deficient miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2006Yuval Yarkoni Abstract CD22-deficient mice are characterized by B cell hyperactivity and autoimmunity. We have constructed knock-in CD22,/, mice, expressing an anti-DNA heavy (H) chain (D42), alone or combined with V,1-J,1 or V,8-J,5 light (L) chains. The Ig-targeted mice produced a lupus-like serology that was age- and sex-dependent. High-affinity IgG autoantibodies were largely dependent on the selection of B cells with a particular H/L combination, in which a non-transgenic, endogenous L,chain was assembled by secondary rearrangements through the mechanism of receptor editing. Moreover, we present evidence that these secondary rearrangements are very prominent in splenic peripheral B cells. Since CD22 is primarily expressed on the surface of peripheral B cells, we propose a model for the development of a lupus-like autoimmune disease by a combination of peripheral receptor editing and abnormal B cell activation. [source] Desmoglein-3 is a target autoantigen in spontaneous canine pemphigus vulgarisEXPERIMENTAL DERMATOLOGY, Issue 2 2003Thierry Olivry Abstract: Pemphigus vulgaris (PV) is an autoimmune blistering skin disease of humans and companion animals. In human patients, PV is associated with the production of IgG autoantibodies specific for keratinocyte desmosomal glycoproteins of the cadherin family. The purpose of this study was to determine whether antikeratinocyte IgG autoantibodies were present in the skin and serum of dogs with PV, and also to identify the canine PV autoantigen(s) targeted by circulating autoantibodies. Eleven dogs were selected because of the microscopic demonstration of suprabasal epithelial acantholysis. Direct immunofluorescence revealed the presence of IgG autoantibodies bound to the membrane of keratinocytes in skin biopsy specimens of 8/9 dogs (89%). Using indirect immunofluorescence, serum-circulating IgG autoantibodies were found in 10/11 (91%) and 5/11 (45%) dogs, using normal canine gingiva and cultured canine oral keratinocytes, respectively. By immunoblotting using cultured canine oral keratinocyte protein lysates, IgG autoantibodies from 7/9 (78%) tested dogs recognized a 130-kDa antigen that comigrated with that identified by rabbit polyclonal antibodies raised against desmoglein-3. This 130 kDa antigen was confirmed to represent the canine equivalent of human desmoglein-3 by immunoprecipitation-immunoblotting. The results of these studies provide evidence that the canine desmoglein-3 homologue is a major autoantigen in dogs with PV. These observations further establish spontaneous canine PV as a natural model for research on pathogenesis, etiology and novel therapeutic approaches for this disease of humans. [source] Pemphigus vegetans , immunopathological findings in a rare variant of pemphigus vulgarisJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 3 2010Babak Monshi Summary A patient with painful erosions of the oral cavity and the labia minora developed multifocal blisters in inter-triginous areas. These blisters eroded and evolved into papillomatous erosive vegetations. Histopathology and immunopathological investigations confirmed the diagnosis of pemphigus vegetans, mediated by IgG autoantibodies. The circulating IgG1 and IgG4 autoantibodies were exclusively directed against desmoglein 3, as shown by ELISA and indirect immunofluorescence studies. These IgG1 and IgG4 isotypes were also in vivo bound, as demonstrated with immunoperoxidase staining of perilesional skin. Our clinical, biochemical and immunopathological observations confirm the hypothesis that pemphigus vegetans is a variant of pemphigus vulgaris. [source] Novel recombinant congenic mouse strain developing arthritis with enthesopathyPATHOLOGY INTERNATIONAL, Issue 7 2008Shiro Mori Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp- lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ- lpr/lpr (C3H/lpr). In MRL/lpr × (MRL/lpr × C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH- lpr/lpr -RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy. [source] What's new in bullous pemphigoidTHE JOURNAL OF DERMATOLOGY, Issue 3 2010Hideyuki UJIIE Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP patients have autoantibodies against type XVII collagen (COL17, also called BP180 or BPAG2), a type II transmembrane protein that spans the lamina lucida and projects into the lamina densa of the epidermal basement membrane. The non-collagenous 16A domain of COL17 is considered to contain pathogenic epitopes of BP. The transfer of immunoglobulin (Ig)G from BP patients fails to cause blisters on mouse skin probably due to differences between humans and mice in the amino acid sequence of NC16A pathogenic epitope of COL17. Passive transfer of rabbit IgG antibodies against the murine homolog of human COL17 NC16A triggers immune reactions to COL17 in mice, including complement activation, mast cell degranulation and neutrophilic infiltration, resulting in dermal,epidermal separation. Recent studies using COL17-humanized mice that express human COL17 but lack murine COL17 were the first to demonstrate the pathogenicity of anti-COL17 human BP IgG autoantibodies in vivo. These new findings provide a greater understanding of BP pathomechanisms and facilitate the development of novel specific and efficient therapeutic strategies for BP. [source] ORIGINAL ARTICLE: Anti-Elastin Antibodies and Elastin Turnover in Normal Pregnancy and Recurrent Pregnancy LossAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Emiliana Konova Problem, The aim of this study was to investigate elastin turnover and autoimmunity in patients with a history of recurrent pregnancy loss (RPL) and during normal pregnancy. Method of study, Anti-,-elastin and anti-tropoelastin IgG and IgM antibodies were measured by a home-made ELISA in serum samples of 60 medically and obstetrically normal pregnant women, classified to three trimester groups, 18 female patients with RPL and 18 healthy non-pregnant women with a history of successful pregnancies. One way analyses of variance and Least Significant Difference method were used for a statistical analysis. Results, Anti-,-elastin IgG autoantibodies were significantly decreased in the third trimester pregnant women. IgM anti-,-elastin autoantibodies were significantly decreased in all pregnancy groups compared with the controls. Synthesis/degradation ratio of elastin was significantly increased in the third trimester pregnancy group, suggesting decreased elastin degradation during this period of pregnancy. Comparing the RPL patients with the healthy non-pregnant controls showed a significantly increased anti-,-elastin IgG antibody and significantly decreased synthesis/degradation ratio in the patient's group, suggesting increased elastin degradation in RPL. Conclusion, Elastin degradation is decreased during normal pregnancy. Increased anti-elastin IgG antibodies may contribute to the pathogenesis of pregnancy losses. [source] Decrease in glomerulonephritis and Th1-associated autoantibody production after progesterone treatment in NZB/NZW miceARTHRITIS & RHEUMATISM, Issue 6 2009Grant C. Hughes Objective While estrogen treatment exacerbates disease in models of systemic lupus erythematosus (SLE), the effects of progesterone are unclear. This study was undertaken to assess the effects of continuous progesterone treatment on autoantibody production and spontaneous glomerulonephritis (GN) in a mouse model of SLE. Methods Female (NZB × NZW)F1 (NZB/NZW) mice were treated with vehicle, 2 mg of depot medroxyprogesterone acetate (DMPA), or 10 mg of DMPA every 6 weeks. Survival, proteinuria, and serum anti,double-stranded DNA (anti-dsDNA) levels were monitored. At 39 weeks of age, kidneys were analyzed for abnormalities and glomerular accumulation of IgG subclasses and C3. Spleen leukocyte subsets were also analyzed. Results DMPA treatment reduced mortality in a dose-dependent manner in association with reduced proteinuria and glomerular damage. High-dose DMPA treatment resulted in a reduction of total serum IgG and IgG2a anti-dsDNA antibody levels, whereas IgG1 anti-dsDNA antibody levels were modestly increased. High-dose DMPA reduced glomerular accumulation of IgG1, IgG2a, IgG3, and complement, while low-dose DMPA decreased glomerular IgG2a and IgG3 levels compared with vehicle treatment. Conclusion Our findings indicate that treatment of premorbid female NZB/NZW mice with DMPA reduces mortality and attenuates spontaneous GN, likely through multiple mechanisms, including altered ratios of protective Th2-related IgG antibodies versus nephritogenic Th1-related IgG autoantibodies. Thus, estrogen and progesterone may have disparate effects on lupus autoimmunity, lending new significance to observed hormonal imbalances in patients with SLE. These data also suggest that treatment of SLE patients with DMPA may have therapeutic benefit. [source] Childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type VII collagen: case report and review of the literatureBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006M. Mayuzumi Summary Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies to type VII collagen, a major component of anchoring fibrils. Most patients with EBA are adult and develop autoantibodies to the noncollagenous (NC) 1 domain of type VII collagen. We describe a 4-year-old Japanese boy presenting pruritic vesicles and tense blisters over his whole body. Immunofluorescence studies revealed linear IgG/C3 deposits along the dermal,epidermal junction of the patient's skin, and circulating IgG autoantibodies mapping to the dermal side of 1 M NaCl-split skin. By immunoblotting analysis using dermal extracts as a substrate, the patient's IgG antibodies labelled a 290-kDa protein corresponding to type VII collagen. Immunoblotting studies using recombinant proteins demonstrated that the patient's circulating autoantibodies recognized not only the NC1 but also the NC2 domain of type VII procollagen. Review of the previously reported cases and the present case suggested that patients with EBA with autoantibodies to regions other than the NC1 domain are all children younger than 10 years of age with clinical features of an inflammatory phenotype. [source] Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severityBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006N. Oyama Summary Background, Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. Objectives, To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Methods, Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Results, Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), ,4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) ,4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to ,4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Conclusions, Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP. [source] A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004M. Aoki-Ota Summary Background, Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3,/, mice to Rag2,/, immunodeficient mice that expressed Dsg3. Objectives, We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3,/, mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. Methods, We adoptively transferred naive Dsg3,/, splenocytes into Rag2,/, mice and compared their PV phenoytpe with those mice receiving immunized Dsg3,/, splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. Results, Mice that received naive Dsg3,/, splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3,/, mice were essential for the production of anti-Dsg3 IgG antibodies. Conclusions, Dsg3-specific naive lymphocytes in Dsg3,/, mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets. [source] Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin ECLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002M. N. Sato Summary Background The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy. Objective To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated. Methods A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay. Results IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen. Conclusions This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy. [source] Diagnosis of pemphigus by ELISA: a critical evaluation of two ELISAs for the detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2000Experimental dermatology, Original article Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are characterized by autoantibodies to the desmosomal glycoproteins desmoglein 3 (Dsg 3) and Dsg 1 (Dsg 1), respectively. In this study, two enzyme-linked immunosorbent assays (ELISA) which detect IgG autoantibodies to Dsg 1 and Dsg 3 have been evaluated. A total of 317 normal and disease controls, 82 patients with PV and 25 with PF were studied. The Dsg 3 ELISA was positive in all 34 patients with untreated PV and the Dsg 1 ELISA was positive in all 10 with untreated PF. When patients undergoing treatment were included, the sensitivities fell to 95% and 92%, respectively, but still compared favourably to the sensitivity of indirect immunofluorescence which was 79% in PV and 84% in PF. All PF sera were negative in the Dsg 3 ELISA and the specificity of both assays was 98% or greater. Large numbers of samples could be analysed simultaneously over a relatively short time period. The Dsg 1 and Dsg 3 ELISAs also provided objective, quantitative, reproducible data which allowed differentiation of PV from PF and in view of these advantages, they are likely to become a routine technique in diagnostic laboratories. [source] Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin ECLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2002M. N. Sato Summary Background The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy. Objective To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated. Methods A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay. Results IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen. Conclusions This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy. [source] | ||||||||||||||||||||||