Wegener's granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin.
Wegener's granulomatosis (WG) is a severe autoimmune disorder ranging from localized granulomatous disease to generalised anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A previous analysis of immunoglobulin heavy chain genes derived from tissue, i.e. Wegener's granuloma indicated selection and affinity maturation towards local antigen(s). The current study focused on determining the specificity of immunoglobulins from distinct B lymphocytes out of Wegener's granuloma. Four pairs of variable region immunoglobulin light and heavy chain genes, isolated before, were recombinantly expressed using the baculovirus/insect cell system. These immunoglobulins were then analysed for their antigenic target employing a protein macroarray based upon a human fetal brain tissue cDNA expression library. The lysosomal transmembrane protein 9B, a key regulator for TNFα activation, was identified as the putative antigenic target of two immunoglobulins and a tetraspanin, which might play a role in leukocyte activation and motility, was identified as the putative antigenic target of another one. Recombinant monoclonal antibodies out of Wegener's granuloma represent a new tool aiding in elucidation of its and WG immunopathogenesis.
Thurner
Lorenz
L
Saarland University Medical School, José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Homburg/Saar, Germany. lorenz.thurner@web.de
Müller
Antje
A
Cérutti
Martine
M
Martin
Thierry
T
Pasquali
Jean-Louis
JL
Gross
Wolfgang L
WL
Preuss
Klaus-Dieter
KD
Pfreundschuh
Michael
M
Voswinkel
Jan
J
D000595:Amino Acid Sequence; D000918:Antibody Specificity / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D015723:Gene Library; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D040081:Protein Array Analysis; D059470:Tetraspanins
D001323:Autoantibodies; D001324:Autoantigens; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C467804:TMEM9 protein, human; C404405:TSPAN7 protein, human; D059470:Tetraspanins