Clonal B-cell populations in patients with idiopathic thrombocytopenic purpura

Harst, D van der; Jong, D. de; Limpens, Jacqueline; Kluin, Ph. M.; Rozier, Y.; Ommen, G.J.B. van; Brand, A.

doi:10.1182/blood.v76.11.2321.2321

Cited by 38 publications

(5 citation statements)

References 16 publications

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“…ITP is a primary autoimmune disease that causes thrombocytopenia from autoantibody‐producing B cells with no other recognized underlying cause (Aster et al , 1998; Davidson & Diamond, 2001). There is debate as to whether ITP can be conceptualized as a B‐cell disorder with oligoclonal antibody production, or whether it is a polyclonal disorder (van der Harst et al , 1990; Christie et al , 1993; Shimomura et al , 1996; McMillan, 2000a,b).…”

Section: Discussionmentioning

confidence: 99%

“…There is debate as to whether ITP is an oligoclonal or polyclonal autoantibody‐producing disorder (van der Harst et al , 1990; Christie et al , 1993; Shimomura et al , 1996; Kelton & Bussel, 2000). This led to the question of whether or not there is a pattern of IgG subclass distribution associated with ITP that may account for the clinical diversity or provide insight into the nature of the autoantibody production.…”

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confidence: 99%

“…Traditionally, oligoclonality is investigated in a number of ways, including the documentation of restricted B‐ or T‐cell populations, in ITP. van der Harst et al (1990) used blood and spleen lymphocytes to detect B‐cell populations using kappa‐lambda flow cytometry and DNA analysis. They reported that 10 patients with ITP had clonal B‐cell populations with three of these patients having oligoclonal characteristics.…”

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confidence: 99%

“…They reported that 10 patients with ITP had clonal B‐cell populations with three of these patients having oligoclonal characteristics. They hypothesized that ITP represents an oligo(clonal) B‐cell proliferative disorder (van der Harst et al , 1990). Christie et al (1993) used platelet antibody light chain analysis, flow cytometry, Southern blot analysis and polymerase chain reaction to conclude that clonal B cells are common in ITP.…”

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confidence: 99%

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The IgG subclasses of platelet‐associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

Chan¹,

Moore²,

Finch

et al. 2003

Br J Haematol

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Summary. The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n ¼ 31) and healthy controls (n ¼ 30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity ¼ 73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity ¼ 91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity ¼ 92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity ¼ 83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n ¼ 14) or with other IgG subclass antibodies (n ¼ 19). However, there were also patients with only IgG2 (n ¼ 2), IgG3 (n ¼ 3) or IgG4 (n ¼ 3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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The IgG subclasses of platelet‐associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

Chan¹,

Moore²,

Finch

et al. 2003

Br J Haematol

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“…We found preferential usage of the rearranged IGHV4–28/IGHJ4 gene in circulating IgG B cells in ITP. Oligoclonal proliferation of B cells has previously been reported, but the structural information of BCRs in primary ITP was unclear 21 . Roark et al .…”

Section: Discussionmentioning

confidence: 99%

High-throughput sequencing of IgG B-cell receptors reveals frequent usage of the rearranged IGHV4–28/IGHJ4 gene in primary immune thrombocytopenia

Hirokawa

Fujishima

Togashi

et al. 2019

Sci Rep

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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.

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