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High-throughput sequencing of IgG B-cell receptors reveals frequent usage of the rearranged IGHV4-28/IGHJ4 gene in primary immune thrombocytopenia.
- Source :
-
Scientific reports [Sci Rep] 2019 Jun 14; Vol. 9 (1), pp. 8645. Date of Electronic Publication: 2019 Jun 14. - Publication Year :
- 2019
-
Abstract
- Primary immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia caused by IgG anti-platelet autoantibodies and represents an organ-specific autoimmune disorder. Although the glycoprotein (GP)IIb/IIIa and GPIb/IX have been shown to be targets for autoantibodies, the antigen specificity of autoantibodies is not fully elucidated. To identify the characteristics of IgG B-cell receptor (BCR) repertoires in ITP, we took advantage of adaptor-ligation PCR and high-throughput DNA sequencing methods for analyzing the clone-based repertoires of IgG-expressing peripheral blood B cells. A total of 2,009,943 in-frame and 315,469 unique reads for IGH (immunoglobulin heavy) were obtained from twenty blood samples. Comparison of the IGHV repertoires between patients and controls revealed an increased usage of IGHV4-28 in ITP patients. One hundred eighty-six distinct IGHV4-28-carrying sequences were identified in ITP patients and the majority of these clones used an IGHJ4 segment. The IGHV4-28/IGHJ4-carrying B-cell clones were found in all ITP patients. Oligoclonal expansions of IGHV4-28/IGHJ4-carrying B cells were accompanied by multiple related clones with single amino substitution in the CDR3 region suggesting somatic hypermutation. Taken together, the expansion of IGHV4-28/IGHJ4-carrying IgG-expressing B cells in ITP may be the result of certain antigenic pressure and may provide a clue for the immune pathophysiology of ITP.
- Subjects :
- Adult
Amino Acid Sequence
Clone Cells
Complementarity Determining Regions chemistry
Humans
Middle Aged
Somatic Hypermutation, Immunoglobulin genetics
Vaccination
Gene Rearrangement
High-Throughput Nucleotide Sequencing
Immunoglobulin G genetics
Purpura, Thrombocytopenic, Idiopathic genetics
Purpura, Thrombocytopenic, Idiopathic immunology
Receptors, Antigen, B-Cell genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31201346
- Full Text :
- https://doi.org/10.1038/s41598-019-45264-2