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Molecular characterization of the variable domains of an αIIbβ3‐specific immunoglobulin M κ platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between αIIbβ3 integrin antibodies
Author(s) -
Jennings Nicola S.,
Harmer Ian J.,
Campbell Kate,
Stafford Prachi,
Smith Graham A.,
Metcalfe Paul,
Benton M. Ann,
Marsh Judith C.W.,
Ouwehand Willem H.
Publication year - 2007
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2006.01142.x
Subject(s) - cold agglutinin , antibody , immunology , rituximab , medicine , chemistry
BACKGROUND: Cold hemagglutinins are generally immunoglobulin M (IgM) κ antibodies reactive at temperatures below 37°C and if of high titer may cause hemolysis. Platelet (PLT) cold agglutinins (CAs) are rare and poorly characterized. A detailed molecular characterization of the variable domains of a pathologic, PLT‐reactive, CA is presented. CASE REPORT: A 70‐year‐old woman was admitted with rectal bleeding accompanied by widespread petechiae, bruising, tongue and buccal mucosa bleeding, and epistaxes and proved refractory to HLA‐ and HPA‐matched PLTs. Detailed investigation showed monoclonal heavy‐chain gene rearrangement with an IgM paraprotein of 3.3 g per L and a trace of κ Bence Jones protein in the urine, compatible with a diagnosis of secretory B‐cell non‐Hodgkin's lymphoma (B‐NHL). PLT antibody (PAIg) investigations revealed a potent IgM κ PLT CA. Sequencing of the rearranged variable domain genes of the malignant clone together with idiotype‐specific antibodies obtained by DNA‐based immunization of rabbits and matrix‐assisted laser desorption/ionization–time‐of‐flight analysis of the PAIgM provided a irrefutable link between the thrombocytopenia, the IgM paraprotein, and the PAIgM against αIIbβ3. The thrombocytopenia and bleeding were refractory to standard treatment and PLT transfusion, but treatment with rituximab resulted in a recovery of the PLT count and a complete remission of B‐NHL. CONCLUSION: The IgM κ paraprotein derived from the malignant B‐cell clone was a potent and clinically significant CA against αIIbβ3. The testing for PLT CAs in patients with a paraprotein and refractory to matched PLTs may aid the selection of appropriate treatment.