0000000000700740

AUTHOR

Mareike Lorenz

showing 3 related works from this author

Human antiphospholipid antibodies induce TNFα in monocytes via Toll-like receptor 8

2009

The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or venous thromboses, pregnancy loss and the presence of antiphospholipid antibodies (aPL). One of the discussed mechanisms of this thrombotic activity in APS patients is attributed to TNFalpha secretion in monocytes after aPL stimulation. To investigate this mechanism in detail, we employed a monoclonal aPL and IgG fractions of APS patients for stimulation of human peripheral monocytes. Stimulation with this monoclonal aPL resulted in an increased expression and secretion of TNFalpha, caused by specific upregulation of TLR8 mRNA and protein expression levels. To confirm the specificity of this finding we could d…

medicine.medical_specialtymedicine.drug_classBlotting WesternImmunologyEnzyme-Linked Immunosorbent AssayStimulationCell SeparationBiologyMonoclonal antibodyPeripheral blood mononuclear cellMonocytesProinflammatory cytokineDownregulation and upregulationimmune system diseasesAntiphospholipid syndromeInternal medicinemedicineHumansImmunology and AllergyReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaAntibodies MonoclonalHematologyAntiphospholipid SyndromeFlow Cytometrymedicine.diseaseEndocrinologyToll-Like Receptor 8MonoclonalImmunologyAntibodies AntiphospholipidElectrophoresis Polyacrylamide GelTumor necrosis factor alphaImmunobiology
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Structural and functional characterization of a human IgG monoclonal antiphospholipid antibody

2009

Antiphospholipid antibodies (aPL) are likely involved in the pathogenesis of the antiphospholipid syndrome (APS). This study analyzes the structural and functional characteristics of a human monoclonal aPL (HL7G) from the IgG2 subtype with λ light chains generated from a patient with primary APS and recurrent cerebral microemboli. DNA encoding the variable region of heavy and light chains of the antibody was sequenced, analyzed, and compared to HL5B a previously described monoclonal aPL from the same patient. Both antibodies are derived from the same germline genes. HL7G had similar but more extensive somatic mutations in the CDR1 and 2 regions than HL5B, indicating that both antibodies are…

MaleCardiolipinsmedicine.drug_classImmunologySomatic hypermutationComplementarity determining regionMonoclonal antibodyImmunoglobulin light chainThromboplastinAntigenimmune system diseasesAntiphospholipid syndromemedicineHumansImmunology and AllergyneoplasmsCells CulturedMolecular StructurebiologyAntibodies MonoclonalT-Lymphocytes Helper-InducerHematologyMiddle AgedAntiphospholipid Syndromemedicine.diseaseComplementarity Determining RegionsMolecular biologybeta 2-Glycoprotein IImmunoglobulin GImmunologyMonoclonalAntibodies Antiphospholipidbiology.proteinSomatic Hypermutation ImmunoglobulinAntibodyImmunobiology
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TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic …

2009

TLRs represent the first line of defense against invading pathogens in the innate immune system. Certain cytokines are important mediators and essentially necessary to assure an appropriately regulated immune response. Recent data gave initial evidence that IL-1beta is one of the most relevant members of these regulating cytokines. We investigated the induction of IL-1beta production in monocytes and pDCs stimulated with ligands for TLR7 and TLR8 and with antiphospholipid antibodies (aPL). Using human monocytes and pDCs for stimulation with specific TLR7 and TLR8 ligands such as resiquimod (R848) and single stranded RNA (RNA42) as well as with a human monoclonal aPL HL5B resulted in a speci…

Malemedicine.drug_classImmunologyInterleukin-1betaCaspase 1Enzyme-Linked Immunosorbent AssayCell SeparationBiologyRegulatory Sequences Nucleic AcidMonoclonal antibodyLigandsMonocytesProinflammatory cytokinechemistry.chemical_compoundImmune systemmedicineImmunology and AllergyHumansInnate immune systemCaspase 1ImidazolesHematologyTLR7Dendritic CellsTLR8Oligonucleotides AntisenseAntiphospholipid SyndromeFlow CytometrychemistryToll-Like Receptor 7Toll-Like Receptor 8Enzyme InductionImmunologyAntibodies AntiphospholipidRNAFemaleResiquimodImmunobiology
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