17 results on '"HUMAN AUTOANTIBODIES"'
Search Results
2. Trichinella spiralis shares epitopes with human autoantigens
- Author
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Ivana Radovic, Alisa Gruden-Movsesijan, Natasa Ilic, Marija Mostarica-Stojkovic, and Ljiljana Sofronic-Milosavljevic
- Subjects
human autoantibodies ,Trichinella spiralis antigens ,conserved epitopes ,Microbiology ,QR1-502 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Like other helminths, Trichinella spiralis has evolved strategies to allow it to survive in the host organism, including the expression of epitopes similar to those present in either expressed or hidden host antigens. To identify T. spiralis-derived antigens that are evolutionarily conserved in the parasite and its host and that could be responsible for its evasion of the host immune response, we examined the reactivity of six different types of autoantibodies to T. spiralis larvae from muscle. T. spiralis antigens that share epitopes with human autoantigens were identified by assessing the cross-reactivity of autoantibody-containing serum samples with T. spiralis antigens in the absence of specific anti-parasite antibodies. Of the 55 autoantibody-containing human serum samples that we analysed by immunohistological screening, 24 (43.6%) recognised T. spiralis muscle larvae structures such as the subcuticular region, the genital primordium or the midgut. Using Western blots, we demonstrated that the same sera reacted with 24 protein components of T. spiralis muscle larvae excretory-secretory L1 antigens. We found that the human autoantibodies predominantly bound antigens belonging to the TSL1 group; more specifically, the autoantibody-containing sera reacted most frequently with the 53-kDa component. Thus, this protein is a good candidate for further studies of the mechanisms of T. spiralis-mediated immunomodulation.
- Published
- 2012
- Full Text
- View/download PDF
3. Clinical relevance of HEp-2 indirect immunofluorescent patterns
- Subjects
PRIMARY BILIARY-CIRRHOSIS ,CELL NUCLEAR ANTIGEN ,IDIOPATHIC INFLAMMATORY MYOPATHIES ,RHEUMATOLOGY/EUROPEAN LEAGUE ,HUMAN AUTOANTIBODIES ,CLASSIFICATION CRITERIA ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,ANTINUCLEAR ANTIBODIES ,HEALTHY-INDIVIDUALS ,PRIMARY SJOGRENS-SYNDROME - Abstract
The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.
- Published
- 2019
4. Clinical relevance of HEp-2 indirect immunofluorescent patterns
- Author
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Werner Klotz, Wilson de Melo Cruvinel, Minoru Satoh, Jan Damoiseaux, Paulo Luiz Carvalho Francescantonio, Luis Eduardo Coelho Andrade, Carlos Alberto von Mühlen, Orlando Gabriel Carballo, Karsten Conrad, Tsuneyo Mimori, Ignacio García-De La Torre, Marvin J. Fritzler, Edward K. L. Chan, and Manfred Herold
- Subjects
0301 basic medicine ,Anti-nuclear antibody ,Immunology ,Context (language use) ,Disease ,ANA patterns ,Bioinformatics ,ANTINUCLEAR ANTIBODIES ,PRIMARY SJOGRENS-SYNDROME ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,IDIOPATHIC INFLAMMATORY MYOPATHIES ,RHEUMATOLOGY/EUROPEAN LEAGUE ,Daily practice ,Immunology and Allergy ,Medicine ,Clinical significance ,CLASSIFICATION CRITERIA ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,HEALTHY-INDIVIDUALS ,030203 arthritis & rheumatology ,PRIMARY BILIARY-CIRRHOSIS ,Indirect immunofluorescence ,business.industry ,HUMAN AUTOANTIBODIES ,Recommendation ,indirect immunofluorescence ,clinical interpretation ,Fluorescence intensity ,CELL NUCLEAR ANTIGEN ,030104 developmental biology ,Healthy individuals ,business - Abstract
The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.
- Published
- 2019
5. Comparison of assay formats used for the detection of pre-existing anti-drug antibodies against monoclonal antibodies.
- Author
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Pöhler A, Emrich T, Jordan G, Schäfer M, Stubenrauch KG, Staack RF, Zach C, Meir J, and Faigle J
- Subjects
- Antibodies, Monoclonal, Antigen-Antibody Complex
- Abstract
Aim: Assessment of pre-existing anti-drug antibody (preADA) reactivity at early drug development stages can be beneficial for candidate selection. We investigated the applicability of a generic immune-complex anti-drug antibody (ADA) assay for early preADA assessment as an easily available alternative to the commonly used ADA bridging assay. Results: The results confirmed the expected assay difference regarding isotype detectability. Tested drug candidates were identified as preADA-reactive using the immune-complex ADA assay despite its limitation of not being able to detect IgM-type preADAs. Conclusion: We recommend a purpose-driven use of the two assay formats. For the purpose of ranking different Pro329Gly mutation-bearing drug candidates, the immune-complex ADA assay is preferred in the phase before selecting a drug for clinical development.
- Published
- 2022
- Full Text
- View/download PDF
6. Human autoantibodies against early endosome antigen-1 enhance excitatory synaptic transmission
- Author
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Selak, S., Paternain, A.V., Fritzler, M.J., and Lerma, J.
- Subjects
- *
ANTIGENS , *AUTOANTIBODIES , *IMMUNOGLOBULINS , *ENDOCYTOSIS - Abstract
Abstract: Early endosome antigen 1 (EEA1), a peripheral membrane protein associated with the cytoplasmic face of early endosomes, controls vesicle fusion during endocytosis, as extensively studied in non-neuronal cells. In neurons, early endosomes are involved in recycling of synaptic vesicles and neurotransmitter receptors. Since certain patients bearing autoantibodies that target EEA1 develop neurological disease, we studied the subcellular distribution of EEA1 in neurons and the effect on neurotransmission of purified immunoglobulins from the serum of a patient bearing EEA1 autoantibodies. EEA1 was localized in the soma and in the postsynaptic nerve terminals. Electrophysiological recordings in hippocampal slices including purified EEA1 antibodies in the patch pipette solution, revealed a run-up of AMPA, N-methyl-d-aspartate and kainate receptor-mediated excitatory post-synaptic currents recorded from CA3 pyramidal neurons, which was absent in the recordings obtained in the presence of control human immunoglobulin G. Inclusion of human EEA1 antibodies had no effect on inhibitory post-synaptic responses. Recordings in the presence of a dominant-negative C-terminal EEA1 deletion mutant produced a similar effect as observed with human anti-EEA1 antibodies. This specific effect on the excitatory synaptic transmission may be due to the impairment of internalization of specific glutamate receptors and their subsequent accumulation in the synapse. These results may account for the neurological deficits observed in some patients developing EEA1 autoantibodies. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
7. In vitro induction of microglial and endothelial cell apoptosis by cerebrospinal fluids from patients with human African trypanosomiasis
- Author
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Girard, Murielle, Bisser, Sylvie, Courtioux, Bertrand, Vermot-Desroches, Claudine, Bouteille, Bernard, Wijdenes, John, Preud'homme, Jean-Louis, and Jauberteau, Marie-Odile
- Subjects
- *
AFRICAN trypanosomiasis , *CENTRAL nervous system - Abstract
In human African trypanosomiasis, trypanosomes first develop in the blood and lymph (Stage 1), then spread to the central nervous system (CNS) (Stage 2). Disruption of the blood–brain barrier of unknown mechanism occurs in Stage 2 disease. The hypothesis that cerebrospinal fluids (CSF) from African trypanosomiasis patients might contain factor(s) able to induce apoptosis in endothelial cells led us to evaluate this effect by two methods, the TdT-mediated dUTP nick end labelling (TUNEL) method and the measurement of soluble nucleosomes released by apoptotic cells in culture supernatant by ELISA. Apoptosis induction by CSF was also studied with microglial cells, the resident macrophages in the brain, which participate in the blood–brain barrier in the perivascular area. In contrast with control CSF, African trypanosomiasis patients'' CSF induced apoptosis in both microglial and endothelial cells. The results obtained with the two methods correlated well, and showed that Stage 2 CSF induced apoptosis at higher levels in microglial cells, whereas the disease stage was not decisive for apoptosis induction in endothelial cells. We measured soluble Fas ligand (sFasL) and anti-Fas antibodies levels, two potent inducers of the Fas signalling pathway leading to apoptosis, in CSF from African trypanosomiasis patients and controls. CSF from African trypanosomiasis patients contained sFasL, and anti-Fas antibodies at higher levels than in controls. Stage 2 CSF contained more sFasL than Stage 1 CSF, and anti-Fas antibodies were detected only in Stage 2 CSF. Caspase-8 inhibitor effect and statistical data suggest that other pro-apoptotic factors may be involved in some CSF-induced apoptosis. Apoptosis induction may participate in the pathogenesis during African trypanosomiasis, and the presence of sFasL and anti-Fas antibodies may provide new tools for diagnosis and prognosis of the disease. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
8. Anti-idiotypic induced suppression of Sjögren's syndrome associated anti-La autoantibody secretion in vitro.
- Author
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Horsfall, Angela C., Mumford, Patricia A., Venables, P. J. W., and Maini, R. N.
- Subjects
- *
ANTI-idiotypic antibodies , *AUTOANTIBODIES , *IMMUNOREGULATION , *SJOGREN'S syndrome , *T cells , *IMMUNOGLOBULINS - Abstract
Peripheral blood mononuclear cells from patients with Sjögren's Syndrome spontaneously secrete autoantibodies to the La antigen when cultured in vitro. This paper reports that specific IgG autoantibody production in vitro is suppressed by pre-treatment of CD8+ enriched T cells with rabbit polyclonal antibodies to idiotypes borne by circulating autologous anti-La antibodies. Treatment of this T cell subpopulation with anti-idiotypes specific for circulating anti-La antibodies from other patients or for anti-DNA antibodies was without effect on anti-La antibody production. Similarly anti-La anti-idiotypes had no effect on the production of autoantibodies to other ribonucleoprotein antigens such as nRNP/Sm. These data show that CD8+ T cells are the main targets for anti-idiotypic control in vitro. We suggest that the relative deficit of these cells, plus a surfeit of CD4+ T cells at the site of the pathological lesion within the salivary gland permits localized production of autoantibodies. Thus, dysregulation of the idiotypic network could contribute to the pathogenesis of Sjögren's Syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 1988
9. Antibodies against insulin measured by electrochemiluminescence predicts insulitis severity and disease onset in non-obese diabetic mice and can distinguish human type 1 diabetes status
- Author
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Lo Bernice, Swafford Austin DE, Shafer-Weaver Kimberly A, Jerome Lawrence F, Rakhlin Luba, Mathern Douglas R, Callahan Conor A, Jiang Ping, Davison Lucy J, Stevens Helen E, Lucas Carrie L, White Jill, von Borstel Reid, Todd John A, and Lenardo Michael J
- Subjects
NOD mice ,diabetes ,human autoantibodies ,insulin ,electrochemiluminescence ,IAA ,IA ,ECL ,Medicine - Abstract
Abstract Background The detection of insulin autoantibodies (IAA) aids in the prediction of autoimmune diabetes development. However, the long-standing, gold standard 125I-insulin radiobinding assay (RBA) has low reproducibility between laboratories, long sample processing times and requires the use of newly synthesized radiolabeled insulin for each set of assays. Therefore, a rapid, non-radioactive, and reproducible assay is highly desirable. Methods We have developed electrochemiluminescence (ECL)-based assays that fulfill these criteria in the measurement of IAA and anti-insulin antibodies (IA) in non-obese diabetic (NOD) mice and in type 1 diabetic individuals, respectively. Using the murine IAA ECL assay, we examined the correlation between IAA, histopathological insulitis, and blood glucose in a cohort of female NOD mice from 4 up to 36 weeks of age. We developed a human IA ECL assay that we compared to conventional RBA and validated using samples from 34 diabetic and 59 non-diabetic individuals in three independent laboratories. Results Our ECL assays were rapid and sensitive with a broad dynamic range and low background. In the NOD mouse model, IAA levels measured by ECL were positively correlated with insulitis severity, and the values measured at 8-10 weeks of age were predictive of diabetes onset. Using human serum and plasma samples, our IA ECL assay yielded reproducible and accurate results with an average sensitivity of 84% at 95% specificity with no statistically significant difference between laboratories. Conclusions These novel, non-radioactive ECL-based assays should facilitate reliable and fast detection of antibodies to insulin and its precursors sera and plasma in a standardized manner between laboratories in both research and clinical settings. Our next step is to evaluate the human IA assay in the detection of IAA in prediabetic subjects or those at risk of type 1 diabetes and to develop similar assays for other autoantibodies that together are predictive for the diagnosis of this common disorder, in order to improve prediction and facilitate future therapeutic trials.
- Published
- 2011
- Full Text
- View/download PDF
10. Antinuclear human autoantibodies as markers in Nicotiana tabacum pollen tubes
- Author
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Rita Vignani, R. Marcolongo, Mauro Cresti, Gabriella Morozzi, Antonio Tiezzi, and C. Poggialini
- Subjects
medicine.diagnostic_test ,Confocal laser scanning microscope ,Nicotiana tabacum ,fungi ,Autoantibody ,food and beverages ,Confocal microscopy ,Human autoantibodies ,Immunofluorescence ,Pollen tube ,Plant Science ,Biology ,biology.organism_classification ,confocal microscopy ,Molecular biology ,pollen tube ,law.invention ,lcsh:QK1-989 ,law ,lcsh:Botany ,Botany ,medicine ,immunofluorescence - Abstract
In the present paper we report on the use of antinuclear human autoantibodies as specific markers in Nicotiana tabacum pollen tubes. The antibodies have been tested by fluorescence techniques using a confocal laser scanning microscope. All the antibodies showed specifc labelling pattern and the results, although preliminary in nature, could open new perspectives of research.
- Published
- 2014
11. Antibodies against insulin measured by electrochemiluminescence predicts insulitis severity and disease onset in non-obese diabetic mice and can distinguish human type 1 diabetes status
- Author
-
Kimberly Shafer-Weaver, John A. Todd, Lawrence F. Jerome, Jill White, Austin D. Swafford, Michael J. Lenardo, Conor A Callahan, Luba Rakhlin, Carrie L. Lucas, Reid von Borstel, Ping Jiang, Helen Stevens, Bernice Lo, Douglas R. Mathern, L. J. Davison, Davison, Lucy [0000-0002-1920-0817], and Apollo - University of Cambridge Repository
- Subjects
medicine.medical_treatment ,Insulin Antibodies ,lcsh:Medicine ,32 Biomedical and Clinical Sciences ,Nod ,Mice ,Radioligand Assay ,0302 clinical medicine ,electrochemiluminescence ,Mice, Inbred NOD ,Insulin-Secreting Cells ,Electrochemistry ,Medicine ,3202 Clinical Sciences ,NOD mice ,Medicine(all) ,0303 health sciences ,IAA ,Diabetes ,General Medicine ,3. Good health ,human autoantibodies ,Disease Progression ,Female ,Radiobinding assay ,4.2 Evaluation of markers and technologies ,medicine.medical_specialty ,insulin ,030209 endocrinology & metabolism ,Autoimmune Disease ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Clinical Research ,Diabetes mellitus ,Internal medicine ,Animals ,Humans ,Metabolic and endocrine ,030304 developmental biology ,Autoantibodies ,Type 1 diabetes ,ECL ,business.industry ,IA ,Biochemistry, Genetics and Molecular Biology(all) ,Insulin ,Research ,Prevention ,lcsh:R ,Autoantibody ,Reproducibility of Results ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,Endocrinology ,Diabetes Mellitus, Type 1 ,ROC Curve ,Immunology ,Luminescent Measurements ,business ,4 Detection, screening and diagnosis ,Insulitis - Abstract
Background The detection of insulin autoantibodies (IAA) aids in the prediction of autoimmune diabetes development. However, the long-standing, gold standard 125I-insulin radiobinding assay (RBA) has low reproducibility between laboratories, long sample processing times and requires the use of newly synthesized radiolabeled insulin for each set of assays. Therefore, a rapid, non-radioactive, and reproducible assay is highly desirable. Methods We have developed electrochemiluminescence (ECL)-based assays that fulfill these criteria in the measurement of IAA and anti-insulin antibodies (IA) in non-obese diabetic (NOD) mice and in type 1 diabetic individuals, respectively. Using the murine IAA ECL assay, we examined the correlation between IAA, histopathological insulitis, and blood glucose in a cohort of female NOD mice from 4 up to 36 weeks of age. We developed a human IA ECL assay that we compared to conventional RBA and validated using samples from 34 diabetic and 59 non-diabetic individuals in three independent laboratories. Results Our ECL assays were rapid and sensitive with a broad dynamic range and low background. In the NOD mouse model, IAA levels measured by ECL were positively correlated with insulitis severity, and the values measured at 8-10 weeks of age were predictive of diabetes onset. Using human serum and plasma samples, our IA ECL assay yielded reproducible and accurate results with an average sensitivity of 84% at 95% specificity with no statistically significant difference between laboratories. Conclusions These novel, non-radioactive ECL-based assays should facilitate reliable and fast detection of antibodies to insulin and its precursors sera and plasma in a standardized manner between laboratories in both research and clinical settings. Our next step is to evaluate the human IA assay in the detection of IAA in prediabetic subjects or those at risk of type 1 diabetes and to develop similar assays for other autoantibodies that together are predictive for the diagnosis of this common disorder, in order to improve prediction and facilitate future therapeutic trials.
- Published
- 2016
12. Trichinella spiralis shares epitopes with human autoantigens
- Author
-
Marija Mostarica-Stojkovic, Ljiljana Sofronic-Milosavljevic, Alisa Gruden-Movsesijan, Ivana Radovic, and Natasa Ilic
- Subjects
Microbiology (medical) ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Blotting, Western ,030231 tropical medicine ,Trichinella spiralis ,Antibodies, Helminth ,lcsh:QR1-502 ,Enzyme-Linked Immunosorbent Assay ,Cross Reactions ,Autoantigens ,lcsh:Microbiology ,Epitope ,030308 mycology & parasitology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Animals ,Humans ,Parasite hosting ,0303 health sciences ,biology ,conserved epitopes ,Autoantibody ,Midgut ,biology.organism_classification ,Virology ,3. Good health ,Trichinella spiralis antigens ,Antigens, Helminth ,human autoantibodies ,biology.protein ,Antibody - Abstract
Like other helminths, Trichinella spiralis has evolved strategies to allow it to survive in the host organism, including the expression of epitopes similar to those present in either expressed or hidden host antigens. To identify T. spiralis-derived antigens that are evolutionarily conserved in the parasite and its host and that could be responsible for its evasion of the host immune response, we examined the reactivity of six different types of autoantibodies to T. spiralis larvae from muscle. T. spiralis antigens that share epitopes with human autoantigens were identified by assessing the cross-reactivity of autoantibody-containing serum samples with T. spiralis antigens in the absence of specific anti-parasite antibodies. Of the 55 autoantibody-containing human serum samples that we analysed by immunohistological screening, 24 (43.6%) recognised T. spiralis muscle larvae structures such as the subcuticular region, the genital primordium or the midgut. Using Western blots, we demonstrated that the same sera reacted with 24 protein components of T. spiralis muscle larvae excretory-secretory L1 antigens. We found that the human autoantibodies predominantly bound antigens belonging to the TSL1 group; more specifically, the autoantibody-containing sera reacted most frequently with the 53-kDa component. Thus, this protein is a good candidate for further studies of the mechanisms of T. spiralis-mediated immunomodulation.
- Published
- 2012
13. Immunoblot assay in differential diagnosis of autoimmune blistering skin diseases
- Subjects
CIRCULATING IGA ,BIOCHEMICAL-CHARACTERIZATION ,LAMINA-LUCIDA AUTOANTIGEN ,HERPES-GESTATIONIS ,HUMAN AUTOANTIBODIES ,BASEMENT-MEMBRANE ZONE ,BULLOUS PEMPHIGOID ANTIGEN ,PARANEOPLASTIC PEMPHIGUS ,EXTRACELLULAR DOMAIN ,LINEAR IGA DERMATOSIS - Published
- 2001
14. Human autoantibodies against early endosome antigen-1 enhance excitatory synaptic transmission
- Author
-
S. Selak, Ana V. Paternain, M.J. Fritzler, and Juan Lerma
- Subjects
Kainic acid ,Patch-Clamp Techniques ,Vesicular Transport Proteins ,Kainate receptor ,Biology ,Neurotransmission ,Inhibitory postsynaptic potential ,Synaptic vesicle ,Hippocampus ,Synaptic Transmission ,Receptor endocytosis ,EEA1 ,chemistry.chemical_compound ,Mice ,Autoimmune Diseases of the Nervous System ,Organ Culture Techniques ,Early endosomes ,Chlorocebus aethiops ,AMPA ,Animals ,Humans ,Autoantibodies ,General Neuroscience ,Pyramidal Cells ,Receptor Aggregation ,Glutamate receptor ,Excitatory Postsynaptic Potentials ,Membrane Proteins ,Kainate ,Middle Aged ,Immunohistochemistry ,Human autoantibodies ,Endocytosis ,Mice, Inbred C57BL ,chemistry ,Receptors, Glutamate ,NMDA ,COS Cells ,Mutation ,Excitatory postsynaptic potential ,Female ,Neuroscience - Abstract
12 páginas, 6 figuras., Early endosome antigen 1 (EEA1), a peripheral membrane protein associated with the cytoplasmic face of early endosomes, controls vesicle fusion during endocytosis, as extensively studied in non-neuronal cells. In neurons, early endosomes are involved in recycling of synaptic vesicles and neurotransmitter receptors. Since certain patients bearing autoantibodies that target EEA1 develop neurological disease, we studied the subcellular distribution of EEA1 in neurons and the effect on neurotransmission of purified immunoglobulins from the serum of a patient bearing EEA1 autoantibodies. EEA1 was localized in the soma and in the postsynaptic nerve terminals. Electrophysiological recordings in hippocampal slices including purified EEA1 antibodies in the patch pipette solution, revealed a run-up of AMPA, N-methyl-d-aspartate and kainate receptor-mediated excitatory post-synaptic currents recorded from CA3 pyramidal neurons, which was absent in the recordings obtained in the presence of control human immunoglobulin G. Inclusion of human EEA1 antibodies had no effect on inhibitory post-synaptic responses. Recordings in the presence of a dominant-negative C-terminal EEA1 deletion mutant produced a similar effect as observed with human anti-EEA1 antibodies. This specific effect on the excitatory synaptic transmission may be due to the impairment of internalization of specific glutamate receptors and their subsequent accumulation in the synapse. These results may account for the neurological deficits observed in some patients developing EEA1 autoantibodies., This work was supported by grants to J.L. from the MCYT (BFI2003-00161) and the European Union (QLG3- CT2001-00929). S.S. was a recipient of a fellowship from the Program of Foreign Doctors and Technologists in Spain (MCYT) and currently is an I3P Program CSIC Research Fellow.
- Published
- 2006
15. Human autoantibodies against early endosome antigen-1 enhance excitatory synaptic transmission
- Author
-
Selak, Sanja, Paternain, Ana V., Fritzler, Marvin J., Lerma Gómez, Juan, Selak, Sanja, Paternain, Ana V., Fritzler, Marvin J., and Lerma Gómez, Juan
- Abstract
Early endosome antigen 1 (EEA1), a peripheral membrane protein associated with the cytoplasmic face of early endosomes, controls vesicle fusion during endocytosis, as extensively studied in non-neuronal cells. In neurons, early endosomes are involved in recycling of synaptic vesicles and neurotransmitter receptors. Since certain patients bearing autoantibodies that target EEA1 develop neurological disease, we studied the subcellular distribution of EEA1 in neurons and the effect on neurotransmission of purified immunoglobulins from the serum of a patient bearing EEA1 autoantibodies. EEA1 was localized in the soma and in the postsynaptic nerve terminals. Electrophysiological recordings in hippocampal slices including purified EEA1 antibodies in the patch pipette solution, revealed a run-up of AMPA, N-methyl-d-aspartate and kainate receptor-mediated excitatory post-synaptic currents recorded from CA3 pyramidal neurons, which was absent in the recordings obtained in the presence of control human immunoglobulin G. Inclusion of human EEA1 antibodies had no effect on inhibitory post-synaptic responses. Recordings in the presence of a dominant-negative C-terminal EEA1 deletion mutant produced a similar effect as observed with human anti-EEA1 antibodies. This specific effect on the excitatory synaptic transmission may be due to the impairment of internalization of specific glutamate receptors and their subsequent accumulation in the synapse. These results may account for the neurological deficits observed in some patients developing EEA1 autoantibodies.
- Published
- 2006
16. Immunoblot assay in differential diagnosis of autoimmune blistering skin diseases
- Author
-
Pas, HH and Translational Immunology Groningen (TRIGR)
- Subjects
CIRCULATING IGA ,BIOCHEMICAL-CHARACTERIZATION ,LAMINA-LUCIDA AUTOANTIGEN ,HERPES-GESTATIONIS ,HUMAN AUTOANTIBODIES ,BASEMENT-MEMBRANE ZONE ,BULLOUS PEMPHIGOID ANTIGEN ,PARANEOPLASTIC PEMPHIGUS ,EXTRACELLULAR DOMAIN ,LINEAR IGA DERMATOSIS - Published
- 2001
17. Mining the human autoantibody repertoire: isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma.
- Author
-
Beerli RR, Bauer M, Fritzer A, Rosen LB, Buser RB, Hanner M, Maudrich M, Nebenfuehr M, Toepfer JA, Mangold S, Bauer A, Holland SM, Browne SK, and Meinke A
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal genetics, Antibodies, Monoclonal isolation & purification, Antibodies, Monoclonal, Humanized genetics, Antibodies, Monoclonal, Humanized immunology, Antibodies, Monoclonal, Humanized isolation & purification, Antibodies, Neutralizing genetics, Antibodies, Neutralizing isolation & purification, Antibody Affinity immunology, Autoantibodies genetics, Autoantibodies isolation & purification, Cell Line, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, Humans, Immunoglobulin Fc Fragments genetics, Immunoglobulin Fc Fragments immunology, Immunoglobulin G genetics, Immunoglobulin G immunology, Interleukin-17 genetics, Molecular Sequence Data, Neutralization Tests, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Recombinant Proteins immunology, Sequence Homology, Amino Acid, Single-Chain Antibodies genetics, Single-Chain Antibodies immunology, Thymoma blood, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Autoantibodies immunology, Interleukin-17 immunology, Thymoma immunology
- Abstract
Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development.
- Published
- 2014
- Full Text
- View/download PDF
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