title: Oligoclonal IgA response in the vascular wall in acute Kawasaki disease.
abstract: Kawasaki Disease (KD) is a potentially fatal acute vasculitis of childhood. Although KD is the leading cause of acquired heart disease in children in developed nations, its pathogenesis remains unknown. We previously reported the novel observation that IgA plasma cells infiltrate the vascular wall in acute KD. We have now examined the clonality of this IgA response in vascular tissue from three fatal cases of KD to determine whether it is oligoclonal, suggesting an Ag-driven process, or polyclonal, suggesting nonspecific B cell activation or a response to a superantigen. We first sequenced VDJ junctions of 44 alpha genes isolated from a primary, unamplified KD vascular cDNA library. Five sets of clonally related alpha sequences were identified, comprising 34% (15 of 44) of the isolated alpha sequences. Furthermore, point mutations consistent with somatic mutation were detected in the related sequences. Next, using formalin-fixed coronary arteries from two additional fatal KD cases, we sequenced VDJ junctions of alpha genes isolated by RT-PCR, and a restricted pattern of CDR3 usage was observed in both. We conclude that the vascular IgA response in acute KD is oligoclonal. The identification of an oligoclonal IgA response in KD strongly suggests that the immune response to this important childhood illness is Ag-driven.
authors.affiliation: Departments of. Pediatrics and Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA. a-rowley@northwestern.edu
authors.forename: A H
authors.initials: AH
authors.lastname: Rowley
authors.forename: S T
authors.initials: ST
authors.lastname: Shulman
authors.forename: B T
authors.initials: BT
authors.lastname: Spike
authors.forename: C A
authors.initials: CA
authors.lastname: Mask
authors.forename: S C
authors.initials: SC
authors.lastname: Baker
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002999:Clone Cells; D003001:Cloning, Molecular; D003331:Coronary Vessels / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D015723:Gene Library; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000096:biosynthesis / Q000235:genetics; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains