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PubMed1993

Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease.

Clinically healthy humans as well as patients suffering from various autoimmune diseases produce natural antibodies against a variety of self-components. Such antibodies have been proposed to carry out a physiologic role in maintaining the integrity of self, as well as potentially destructive roles in the generation of autoimmune diseases. Because human autoantigens, particularly membrane proteins, are usually present in extremely small amounts, it is generally impossible to obtain enough to carry out a detailed characterization of the antibodies or the antigenic determinants recognized. To circumvent this difficulty, we developed synthetic autoantigens predicted from the gene sequence of two functionally critical membrane proteins; the band 3 anion transport protein which is found on all cells, and the T-cell receptor (beta chain) which is the antigen-specific receptor on thymus-derived lymphocytes. We have investigated the natural human IgM and IgG antibody responses to peptides selected on the basis of predicted molecular surface exposure and previously known antigenicity, and correlate levels of binding with changes in age and by comparison with autoimmune diseases. We report that the IgM response to synthetic autoantigens tends to be higher than that of IgG molecules, but significant IgG binding occurs to some peptides. This situation is particularly noticeable in comparison of rheumatoid arthritis patients with normal individuals. Distinct peptide portions of individual molecules are recognized differently by the autochthonous immune system as manifested by age dependence of the response and differential levels of IgM and IgG activity. The synthetic autoantigens that tend to generate the highest amounts of natural antibody are those that are either exposed on the surface of the cell (band 3 peptides) or are exposed in the predicted 3-dimensional folding of the molecule (T-cell receptor beta peptides). Rheumatoid arthritis patients tend to give higher IgM reactivities to both band 3 and Tcr beta peptides than do normals, with this effect being less pronounced in the distinct autoimmune disease systemic lupus erythematosus. Studies of normal humans ranging in age from 20 to 90 years suggest two major patterns for the IgM natural antibody response to synthetic peptides giving high response. The first is that the level of IgM reactivity is high early in life and remains high throughout. The second pattern is one in which the reaction is high in younger individuals, but diminishes substantially in the latter decades of life.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Islet cell autoantigens in insulin-dependent diabetes.

A burgeoning number of antigenic targets of the islet cell autoimmunity in IDD have been identified, and more can be anticipated through improved methods for their identification. The challenge for those investigating the pathogenesis of IDD will be to assign the relative importance of these antigens to the development of the disease, and to resolve whether there is a dominant primary immunologic event that is followed by a series of secondary immunizations to a variety of normally sequestered islet cell antigens in the sequence of pathogenic events that culminate in IDD. One interesting observation that may have potential pathogenic implications is the observation that of all islet cell autoantigens described, only two (i.e., 64 kD/GAD, 38 kD) are reactive in their native configurations, implying that recognition of conformational epitopes is most important. This property argues for primary immunizing agents rather than secondary ones after release of denatured antigens and antigenic recognition through their epitopes. Given the complex and multiple physiological functions of islet cells and the continuous variation in their activity, it is reasonable to speculate that the speed of the progression to IDD could vary between individuals with respect to their insulin needs and the relative activities of their islets. Activated islets may express autoantigens that have only limited expression in quiescent islets. The often times striking variation in the severity of insulitis seen in different islets of a single pancreas may be explained by the level of activity of individual islets. Furthermore, disparity in HLA-DR/DQ associations with disease may involve differences in the immunological recognition of autoantigens. Whereas there is still much to learn, it is clear that disease predictability and disease intervention studies have been enhanced through the identification of the islet cell autoantigens in IDD.

Autoantigens↗
PubMed1994

Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus.

A role for helper T cells in the induction of pathogenic lupus autoantibodies is increasingly supported by data from studies of murine lupus and patients with systemic lupus erythematosus (SLE). However, the poor in vitro function of SLE T cells has hampered the identification and characterization of autoantigen-specific T cells. We used recombinant fusion proteins to study the T cell proliferative response of 31 lupus patients and 27 healthy subjects to a well-characterized SLE autoantigen, the ribosomal P2 protein. Although PBMC from SLE patients showed marked impairment in the proliferative response to the common recall antigen tetanus toxoid when compared with normal subjects, a significantly greater proportion of SLE patients (32%) than normal individuals (0%) showed a T cell response to a recombinant P2 fusion protein. When the SLE patients were subgrouped according to the presence of serum anti-P autoantibody, 7 of 10 anti-P antibody-positive patients, but 0 of 20 anti-P antibody-negative SLE patients, demonstrated > 2,000 cpm [3H]thymidine incorporation and a P2 stimulation index > 5. The specificity of the T cell proliferative response for the P2 protein was confirmed by studies using a second recombinant human P2 fusion protein and by the specific activation of P2-primed T cells by recombinant P2 in secondary cultures. Moreover, the T cell proliferative response to the P2 autoantigen was mediated by CD4-positive T cells and was inhibited by anti-MHC class II antibodies. These data demonstrate the presence of autoantigen-specific T helper cells in patients with SLE and suggest that these T cells drive the production of autoantibodies by B lymphocytes.

Autoantigens↗
PubMed2002

Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity.

The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for Sjögren syndrome. Specific inhibitor of cathepsin S (Clik60) in vitro markedly impaired presentation of an organ-specific autoantigen, 120-kDa alpha-fodrin, by interfering with MHC class II-peptide binding. Autoantigen-specific T cell responses were significantly and dose-dependently inhibited by incubation with Clik60, but not with inhibitor s of cathepsin B or L. Clik60 treatment of mouse salivary gland cells selectively inhibited autopeptide-bound class II molecules. Moreover, the treatment with Clik60 in vivo profoundly blocked lymphocytic infiltration into the salivary and lacrimal glands, abrogated a rise in serum autoantibody production, and led to recovery from autoimmune manifestations. Thus, inhibition of cathepsin S in vivo alters autoantigen presentation and development of organ-specific autoimmunity. These data identify selective inhibition of cysteine protease cathepsin S as a potential therapeutic strategy for autoimmune disease processes.

Animals↗
PubMed2005

Autoantigens act as tissue-specific chemoattractants.

We have investigated the chemoattractant properties of self-antigens associated with autoimmune diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi-protein-coupled receptors (GiPCR). Our initial observation that myositis-associated autoantigens, histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)- and CCR3-expressing leukocytes, while other nonautoantigenic aminoacyl-tRNA synthesases were not, suggested that only self-antigens capable of interacting with receptors on antigen-presenting cells were immunogenic. We next determined that self-antigens associated with autoimmune diseases, e.g., multiple sclerosis or experimental autoimmune encephalomyelitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoimmune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10-100 ng/ml, but did not induce DC maturation until they reached 1000-fold higher concentrations. Interphotoreceptor retinoid-binding protein and retinal arrestin (S-antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)- and/or CXCR3-expressing iDC. However, although S-antigen does not induce EAU in wild-type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue-specific self-antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoimmune responses subsequently develop only in subjects with impaired immunoregulatory function.

Animals↗
PubMed1998

The GM2-1 ganglioside islet autoantigen in insulin-dependent diabetes mellitus is expressed in secretory granules and is not beta-cell specific.

The pancreatic islet monosialo-ganglioside (GM2-1), an autoantigen in insulin-dependent diabetes mellitus (IDDM) recently shown to be the target of autoantibodies associated with diabetes development in relatives of IDDM patients, is islet specific within the pancreas, and its expression is metabolically regulatable. In the present study we sought to establish 1) whether GM2-1 is beta-cell specific, and 2) its intracellular localization. To this end, we analyzed the pattern of ganglioside expression in highly purified beta- and non-beta-cells isolated from rat islets. In addition, ganglioside levels were determined in subcellular fractions of a rat beta-cell line (INS). No qualitative or quantitative difference was found in the pattern of ganglioside expression between beta and non-beta rat islet cells, with GM3, GM2-1, and GD3 gangliosides expressed in both cell populations. Within INS cells, GM2-1 ganglioside was expressed in the fraction containing secretory granules and, to a lesser extent, in plasma membranes; GM3 was expressed in secretory granules, whereas GD3 was found only in plasma membranes. These data indicate that the GM2-1 autoantigen is not beta-cell specific within the islets, in accordance with the observation that this molecule is a target of islet cell autoantibodies that bind to the whole pancreatic islet. Interestingly, this autoantigen is present in secretory granules similarly to other autoantigens in IDDM (insulin, carboxypeptidase H, 38-kDa protein, etc.), suggesting that the autoimmunity to the components of this organelle may be central to the pathogenesis of the disease.

Animals↗
PubMed1994

Potential autoantigens in IDDM. Expression of carboxypeptidase-H and insulin but not glutamate decarboxylase on the beta-cell surface.

Insulin, carboxypeptidase-H (CP-H), and glutamate decarboxylase (GAD) have been identified as potential autoantigens in insulin-dependent diabetes mellitus (IDDM). Previous studies have described immunoreactive insulin as a surface molecule on the plasma membrane of rat islet cells and suggested that cell-surface insulin was derived during exocytosis by the fusion of insulin secretory granules with the beta-cell plasma membrane. These findings predict that insulin and other secretory granule-derived proteins such as the putative autoantigen CP-H may be colocalized with insulin at specific sites of exocytosis on the beta-cell surface. In studies to test this hypothesis, cell-surface staining of dispersed rat islet cells occurred in a granule-like pattern with antibodies for CP-H and insulin. The specificity of the CP-H antiserum was confirmed by immunoblotting and indicated that the antiserum was essentially monospecific for CP-H. Confocal laser microscopy confirmed that immunoreactive staining for CP-H and insulin was confined to the beta-cell surface. Colocalization of CP-H and insulin on the cell surface of beta-cells was demonstrated by double staining with antibodies to CP-H and insulin, and the percentage of beta-cells positive for both of these autoantigens increased twofold with increases in insulin secretion. In contrast, islet cells failed to reveal cell-surface staining for GAD65, another putative autoantigen in IDDM, under either basal or insulin stimulatory conditions or following exposure of islet cells to the cytokines interleukin-1 beta, tumor necrosis factor-alpha, and recombinant human interferon-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543).

Prevention of type 1 diabetes in NOD mice by 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is accompanied by a T-helper (Th) 1/Th2 cytokine shift in the pancreas. The aim of this study was to investigate whether this immune shift also occurs outside of the pancreas and whether it is limited to autoantigen-specific immune responses. NOD mice treated with 1alpha,25(OH)2D3 (5 microg/kg every 2 days) or control vehicle were immunized with GAD65 (p524-543) or ovalbumin (OVA) in the rear footpads. First, we examined T-cell proliferation and cytokine production (via enzyme-linked immunosorbent assay) of draining lymph node cells in vitro with or without peptide rechallenge. Although no differences in proliferation were measured between control and 1alpha,25(OH)2D3-treated mice after in vitro GAD65 rechallenge, a marked shift in cytokine secretion profile was seen in 1alpha,25(OH)2D3-treated mice: interleukin-4 was increased (37 +/- 5 vs. 21 +/- 12 pg/ml in controls, P < 0.005), whereas gamma-interferon levels were decreased (6 +/- 3 vs. 9 +/- 3 ng/ml in controls, P < 0.05). This shift was absent in OVA-primed mice. Second, we measured cytokine profiles by reverse transcriptase-polymerase chain reaction in popliteal lymph nodes at different time points after priming with GAD65 or OVA in vivo. A marked Th1/Th2 shift occurred in 1alpha,25(OH)2D3-treated mice after in vivo priming with GAD65. Again, this shift was absent after OVA immunization. Finally, we measured cytokine profiles after rechallenge with a panel of autoantigens (GAD65, heat shock protein 65, insulin B-chain) and control antigens (OVA, keyhole limpet hemocyanine, myelin proteolipid protein, tetanus toxin) and confirmed the Th1/Th2 shift in autoantigen-injected mice but not in control antigen-injected mice. In conclusion, the immune deviation induced by 1alpha,25(OH)2D3 in NOD mice can also be induced in the peripheral immune system but is limited to pancreatic autoantigens.

Amino Acid Sequence↗
PubMed1993

T cell activation by autoantigens in multiple sclerosis.

A panel of autoantigens (myosin, actin, myelin basic protein MBP, and thyroglobulin) was used to analyze antigen recognition by the peripheral blood leukocytes (PBL) of patients with active and stable multiple sclerosis (MS), patients with other neurological diseases (OND) and healthy individuals. The immune responsiveness was studied by examining the in vitro cell proliferation and the increase in the expression of two T-cell-surface activation markers (the interleukin-2 receptor IL-2R, and a late activation antigen recognized by the 19.2 monoclonal antibody). In MS, autoantigen recognition occurred more frequently than in the other groups and it was manifested by moderate proliferation or marked elevation of the expression of the IL-2R, whereas autoantigen recognition in the other groups concerned essentially the expression of the late activation antigen. Results similar to those described above were obtained with enriched T lymphocytes either in the presence or absence of IL-2. Our results suggest that the peripheral immune system in MS patients may recognize and can be activated by different autoantigens and not only by MBP, and that this response is quantitatively and qualitatively different from that of PBL from OND patients and healthy individuals.

Actins↗
PubMed1995

Autoepitope mapping of the centrosome autoantigen PCM-1 using scleroderma sera with anticentrosome autoantibodies.

We previously characterized a scleroderma serum (serum 1) containing autoantibodies against centrosome autoantigens that have been named PCM-1, PCM-2 and PCM-3. In this study, we analyzed another scleroderma serum (serum 2) reactive with centrosome autoantigens of identical molecular weights to those recognized by serum 1. To further analyze the autoepitope domains in PCM-1 recognized by the autoantibodies present in scleroderma sera, cDNAs encoding different portions of the PCM-1 autoantigen were expressed in bacteria as fusion proteins. The immunoreactivity of the fusion proteins to the scleroderma sera was assayed by immunoblot analysis. Two regions containing autoepitope domains reactive with both sera were identified in the PCM-1 molecule. One is between amino acids 312-706 of the PCM-1 autoantigen, and the other is localized between amino acids 1,433-1,787, indicating that the immune response is oligoclonal. The results are important to clarify the mechanism of induction of anticentrosome autoantibodies. The potential diagnostic and prognostic significance of the autoantibodies for subgroups of scleroderma is discussed.

Animals↗
PubMed2001

Autoantigenic HCgp39 epitopes are presented by the HLA-DM-dependent presentation pathway in human B cells.

It is hypothesized that autoimmune diseases manifest when tolerance to self-Ags fails. One possible mechanism to break tolerance is presentation of self-Ag in an altered form. Most Ags are presented by APCs via the traditional presentation pathway that includes "epitope editing" by intracellular HLA-DM, a molecule that selects for stable MHC-peptide complexes. We were interested in testing the hypothesis that autoreactive MHC-peptide complexes may reach the cell surface by an alternate pathway without being edited by HLA-DM. We selected a cartilage autoantigen human cartilage glycoprotein 39 to which T cell responses are observed in rheumatoid arthritis (RA) patients and some DR(*)04 healthy subjects. RA is genetically associated with certain DRB1 alleles, including DRB1(*)0401 but closely related allele DRB1(*)0402 is either neutral or mildly protective with respect to RA. We generated human B lymphoblastoid cell line cells expressing DR(*)0401 or DR(*)0402 in the presence or absence of intracellular HLA-DM and assessed their ability to present a candidate autoantigen, human cartilage glycoprotein 39. Our results show that the presence of intracellular HLA-DM is critical for presentation of this autoantigen to CD4(+) T cell hybridomas generated from DR(*)04-transgenic mice. Presentation of an autoantigen by the traditional HLA-DM-dependent pathway has implications for Ag presentation events in RA.

Adipokines↗
PubMed2001

Granzyme B proteolysis of a neuronal glutamate receptor generates an autoantigen and is modulated by glycosylation.

Autoimmune processes are initiated when tolerance to self-proteins fails to be established or maintained and immune cells are stimulated by self-Ags. Although intracellular autoantigens are common, the origin of extracellular autoantigens is poorly defined and possibly more dangerous. In this study, we considered a mechanism for the origin of an extracellular autoantigen from the neuronal glutamate receptor subunit 3 (GluR3) in Rasmussen's encephalitis, a severe form of pediatric epilepsy. We demonstrate that specific cleavage of GluR3 by granzyme B (GB), a serine protease released by activated immune cells, can generate the GluR3B autoantigenic peptide, but only if an internal N:-linked glycosylation sequon within the GluR3-GB recognition sequence (ISND*S) is not glycosylated. However, this N:-glycon sequon while glycosylated normally is inefficiently used and glycosylation can fail. These results suggest that GB/N:-glycon sites may escape normal tolerance mechanisms and contribute to autoantibody-mediated immune diseases.

Amino Acid Sequence↗
PubMed2001

Possible role of organ-specific autoantigen for Fas ligand-mediated activation-induced cell death in murine Sjögren's syndrome.

Activation-induced cell death (AICD) is a well-known mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). In this study, we demonstrate that the administration of a soluble form of anti-FasL Ab, FLIM58, results in severe destructive autoimmune exocrinopathy in the murine model of human Sjögren's syndrome (SS), and we found that an organ-specific autoantigen may play an important role on down-modulation of AICD. A high titer of serum autoantibodies against 120-kDa alpha-fodrin autoantigen was detected in the FLIM58-treated mice, and splenic T cell culture supernatants contained high levels of IFN-gamma. In vitro T cell apoptosis assay indicated that FasL-mediated AICD is down-regulated by autoantigen stimulation in spleen cells from the murine SS model, but not from Fas-deficient MRL/lpr mice and FasL-deficient MRL/gld mice. FasL undergo metalloproteinase-mediated proteolytic processing in their extracellular domains, resulting in the release of soluble trimeric ligands (soluble FasL). We showed that the processing of soluble FasL occurs in autoantigen-specific CD4(+) T cells, and that a significant increase in expressions of metalloproteinase-9 mRNA was observed in spleen cells from SS model mice. These findings indicate that the increased generation of soluble FasL inhibits the normal AICD process, leading to the proliferation of effector CD4(+) T cells in the murine SS model.

Animals↗
PubMed2002

Prevention and induction of autoimmune exocrinopathy is dependent on pathogenic autoantigen cleavage in murine Sjögren's syndrome.

The in vivo role of autoantigen cleavage during apoptosis in autoimmune diseases remains unclear. Previously, we found a cleavage product of 120-kDa alpha-fodrin as an important autoantigen in the pathogenesis of primary Sjögren's syndrome (SS). In the murine primary SS model, tissue-infiltrating CD4(+) T cells purified from the salivary glands bear a large proportion of Fas ligand, and the salivary gland duct cells constitutively possess Fas. Infiltrating CD4(+) T cells, but not CD8(+) T cells, identified significant (51)Cr release against mouse salivary gland cells. In vitro studies demonstrated that apoptotic mouse salivary gland cells result in a specific alpha-fodrin cleavage into 120 kDa and that preincubation with caspase inhibitor peptides blocked alpha-fodrin cleavage. In vivo treatment with caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone and N-acetyl-Asp-Glu-Val-Asp-al-CHO into the murine model results in dramatic inhibitory effects on the development of autoimmune lesions and in restoration of sicca syndrome. Furthermore, we found that immunization with recombinant alpha-fodrin protein identical with an autoantigen into normal recipients induced autoimmune lesions similar to SS. These data indicate that prevention and induction of autoimmune exocrinopathy is dependent on autoantigen cleavage via caspase cascade and that caspase inhibitors might provide a new therapeutic option directed at reducing tissue damage in the murine model for SS.

Animals↗
PubMed2004

Nucleotide sequencing of psoriatic arthritis tissue before and during methotrexate administration reveals a complex inflammatory T cell infiltrate with very few clones exhibiting features that suggest they drive the inflammatory process by recognizing autoantigens.

Psoriatic arthritis is an interesting MHC class I allele associated autoimmune disease where injury is likely mediated exclusively by T cells. We used TCR beta-chain nucleotide sequencing to gain insight into the adaptive immune events responsible for this injury and determine whether the numerous oligoclonal expansions of this disease represent extreme determinant spreading among driving clones that recognize autoantigen or were non-Ag-driven, inflammation-related expansions. Because methotrexate suppresses but does not eliminate this inflammation, we hypothesized that clones persisting during methotrexate treatment would likely drive the inflammation. Seventy-six percent of the T cell clones in active tissue were polyclonal and unexpanded, accounting for 31% of transcripts. They were decreased greatly by methotrexate. Strikingly, most expanded clones in the inflamed joint did not persist during methotrexate treatment, were found only in inflammatory sites, exhibited no structural homology to one another, and were either CD4 or CD8 in lineage, suggesting they were non-autoantigen-driven, inflammation-related expansions. Only 12% of the expanded clones could be grouped into clonal sets distinguished by structurally homologous CDR3 beta-chain amino acid motifs suggesting Ag drive. These were exclusively CD8 in lineage, persisted during methotrexate administration, and were present in both joint fluid and blood implying they were candidate driver clones that recognized an autoantigen. However, a major set of putative driver clones exhibited a previously described EBV-specific beta-chain motif, emphasizing that the dominant feature of the disease was activation of multiple clones apparently lacking specificity for an inciting autoantigen.

Amino Acid Sequence↗
PubMed2005

Nuclear autoantigen translocation and autoantibody opsonization lead to increased dendritic cell phagocytosis and presentation of nuclear antigens: a novel pathogenic pathway for autoimmunity?

Autoreactivity in lupus requires the delivery of autoantigens to APCs in a proinflammatory context. It has been proposed that apoptotic cells are a source of lupus autoantigens and targets for autoantibodies. Using a histone H2B-GFP fusion protein as traceable Ag, we show here that lupus autoantibodies, directed against nuclear autoantigens, can opsonize apoptotic cells, enhance their uptake through induction of proinflammatory Fc gammaR-mediated phagocytosis, and augment Ag-specific T cell proliferation by increasing Ag loading. Apoptotic blebs and bodies seemed to be a preferred target of DC phagocytosis, via both "eat-me signals" and Fc gammaR-mediated mechanisms; furthermore, inhibition of nuclear Ag redistribution, by blockade of chromatin fragmentation, could stop binding and opsonization of apoptotic cells by autoantibodies, and inhibited Fc gamma-R-mediated enhancement of phagocytosis. Our results suggest that DC uptake of opsonized histones and other nuclear Ags from apoptotic cells is a novel pathway for the presentation of nuclear Ags in a highly inflammatory context. Blockade of chromatin fragmentation in lupus is a potential therapeutic approach, which could theoretically limit DC access to autoantigens delivered in proinflammatory context, while leaving available for tolerization those delivered in a noninflammatory context.

Active Transport, Cell Nucleus↗
PubMed2003

Possible role of Hsp70 in autoantigen shuttling to the dermo-epidermal junction in systemic lupus erythematosus.

The lupus band is the result of immune complex deposition along the dermo-epidermal junction; such complexes are formed in situ by the interaction of antinuclear antibodies with their respective autoantigens. Dermal autoantigens are released after sun exposure, concurrently a heat shock protein production take place and would participate in autoantigen transfer to the dermo-epidermal junction. In this work the presence of Hsp70 along with the lupus band was investigated by immunofluorescence in twenty SLE skin biopsies. Immune deposits were mainly composed by IgM, IgG and C3 and were found in all lupus biopsies at the dermo-epidermal junction. Immunoreagents were also present into papillary vessels and, with less extent, into epidermal keratinocytes. Hsp70 was present in 60% of lupus biopsies, and was mainly distributed along dermo-epidermal junction and around papillary vessels. Furthermore, by double fluorescence labelling assays, we found that immuno-reactants are co-localized with Hsp70. Our results suggest that Hsp70 would shuttle autoantigens to the dermo-epidermal junction.

Adolescent↗
PubMed1999

[Genes for autoantigens].

Thyroid autoantigens have been well studied in view of the identification corresponding to respective autoantibodies in circulation, which are utilized as a diagnostic or follow-up marker of autoimmune thyroid diseases. There are several thyroid autoantigen genes cloned, such as thyroglobulin (TG), thyroid peroxidase (TPO), thyrotropin receptor (TSHR) and iodine transporter (NIS). Recent progress of the molecular study on thyroid autoantigens has allowed us to examine the characteristic features of these genes. Here we introduce the four representative thyroid autoantigens (TG, TPO, TSHR and NIS) and summarize the specific findings of genetic alteration and the sites of antigenicity corresponding to autoantibodies.

Autoantigens↗