DISTINCT CLONOTYPIC EPSTEIN-BARR VIRUS-INDUCED FATAL LYMPHOPROLIFERATIVE DISORDER IN A PATIENT WITH WISKOTT-ALDRICH SYNDROME

Background. Recently, reports of Epstein-Barr virus (EBV)-induced lymp hoproliferative disorders (LPD) have increased in number among immunos uppressed recipients of organ transplants. The importance of analyzing both the immunoglobulin gene and EBV termini is advocated for the inv estigation of pathogenetic mechanisms for clonal proliferation in EBV- induced LPD; however, the oncogenic mechanisms of EBV-induced LPD rema in unclear. Furthermore, there are very few clonotypic studies of EBV- induced LPD in patients with primary immunodeficiency diseases. The au thors studied the clonality of an EBV-induced fatal LPD in a 20-year-o ld patient with Wiskott-Aldrich syndrome (WAS), an X-linked recessive primary immunodeficiency disease. Methods and Results. An autopsy show ed non-Hodgkin lymphoma of B-cell origin with diffuse large cells in b oth systemic lymph nodes and extranodal organs. Immunohistochemical an d Southern blot analyses showed polyclonal rearrangement of immunoglob ulin genes in most of the lesions except for the pulmonary hilar lymph node. Furthermore, the analysis of restriction fragment length polymo rphism with several fragments from EBV genome indicated that EBV genom es in all lesions were identical; however, a single but different-size d EBV termini was detected in every EBV-positive lesion when probed wi th the EcoRI-Dhet spanning terminal repeat region of EBV. Conclusions. The EBV-induced fatal LPD in a patient with WAS showed the characteri stic clonotype, polyclonal immunoglobulin gene rearrangement, and mono clonal EBV terminal configuration. Furthermore, EBV termini in each le sion varied in size. This particular clonotype implicates several uniq ue pathogenetic mechanisms for clonal proliferation of EBV-induced LPD .