Detection of circulating B cells producing anti-GPIb autoantibodies in patients with immune thrombocytopenia.
BACKGROUND
We previously reported that an enzyme-linked immunospot (ELISPOT) assay for detecting anti-GPIIb/IIIa antibody-secreting B cells is a sensitive method for identifying patients with immune thrombocytopenia (ITP). Here we assessed the clinical significance of measuring circulating B cells producing antibodies to GPIb, another major platelet autoantigen.


METHODS
Anti-GPIb and anti-GPIIb/IIIa antibody-producing B cells were simultaneously measured using ELISPOT assays in 32 healthy controls and 226 consecutive thrombocytopenic patients, including 114 with primary ITP, 25 with systemic lupus erythematosus (SLE), 30 with liver cirrhosis, 39 with post-hematopoietic stem cell transplantation (post-HSCT), and 18 non-ITP controls (aplastic anemia and myelodysplastic syndrome).


RESULTS
There were significantly more circulating anti-GPIb and anti-GPIIb/IIIa antibody-producing B cells in primary ITP, SLE, liver cirrhosis, and post-HSCT patients than in healthy controls (P<0.05 for all comparisons). For diagnosing primary ITP, the anti-GPIb ELISPOT assay had 43% sensitivity and 89% specificity, whereas the anti-GPIIb/IIIa ELISPOT assay had 86% sensitivity and 83% specificity. When two tests were combined, the sensitivity was slightly improved to 90% without a reduction in specificity. In primary ITP patients, the anti-GPIb antibody response was associated with a low platelet count, lack of Helicobacter pylori infection, positive anti-nuclear antibody, and poor therapeutic response to intravenous immunoglobulin.


CONCLUSIONS
The ELISPOT assay for detecting anti-GPIb antibody-secreting B cells is useful for identifying patients with ITP, but its utility for diagnosing ITP is inferior to the anti-GPIIb/IIIa ELISPOT assay. Nevertheless, detection of the anti-GPIb antibody response is useful for subtyping patients with primary ITP.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Masataka
M
Kuwana
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Yuka
Y
Okazaki
Faculty of Science and Engineering, Waseda University, Japan.
Yasuo
Y
Ikeda
D000974:Antibodies, Antinuclear / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007564:Japan; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis* / Q000276:immunology*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D000974:Antibodies, Antinuclear; D019038:Platelet Glycoprotein GPIb-IX Complex