Oligo-monoclonal immunoglobulins frequently develop during concurrent cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infections in patients after renal transplantation

Abstract

In the present study we report that the appearance of oligo-monoclonal immunoglobulins (oligoM-Igs) in the sera of transplanted individuals is concurrent with the detection of coincident active CMV infection and EBV replication. Eighty-four renal allograft patients were monitored with respect to CMV isolation, to CMV conventional serology and humoral response against the EBV trans-activator ZEBRA (an immediate-early antigen also called BZLF1). Titration of anti-ZEBRA antibodies (IgG and IgM) and amount of EBV DNA in serum were evaluated. Using the combination of four techniques (agarose gel electrophoresis, analytical isoelectric focusing, high resolution immunoelectrophoresis, immunofixation electrophoresis), oligoM-Igs were found in 25% of patients after allografting and significantly associated with rejection episodes (P < 0.001). Twenty out of 23 (86%) concurrent CMV/EBV infections were associated with serum oligoM-Igs (P < 0.001). One can thus reasonably assume that a sustained EBV replication following iatrogenic immunosuppression can promote the immunoglobulin heavy chain expression in EBV-infected B lymphocytes. The proliferation of immunoglobulin-secreting clones might occur after active CMV infection, through a transient over-immunosuppression or via immune subversion.

Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma

“…Some studies found associations between occurrence of sMGUS and CMV or EBV reactivation or development of (acute/chronic) GvHD. 19,23,[30][31][32][33][34][35] This suggests that oligoclonal bands may represent the generation of an immune response to infectious agents or that the oligoclonal bands mediate alloimmune reactions after allo-SCT. In our study, we demonstrated a trend towards a higher incidence of post-transplant MGUS in the presence of chronic GvHD, but no association with CMV, EBV, or aspergillus infections.…”

Paraproteinaemia after allo-SCT, association with alemtuzumab-based conditioning and CMV reactivation

“…[4][5][6][7][8][9][10] Post transplant paraproteinaemia has also been described following auto-SCT [11][12][13] and in recipients of solid organ transplants (SOT). [14][15][16][17][18] There is consensus on several points: (1) paraproteinaemia following allo-SCT is frequent; incidence estimates range from 18 to 100% depending on the patient group studied and sensitivity of detection method. 5,9,10 (2) The majority, if not all, of the paraproteins detected are transient.…”

“…7,10 In SOT there is a strong association between both CMV seropositivity and CMV reactivation and paraprotein development. [14][15][16][17][18] Paraproteins have also been associated with primary CMV infection and CMV reactivation in both immunocompetent and post transplant immunosuppressed patients. 22 One study has suggested such an association with CMV following allo-SCT 7 although the number of affected patients was small and the association was not statistically significant.…”

“…In SOT there is a strong association between CMV infection and/or reactivation and the development of paraproteinaemia, [14][15][16][17][18] an association suggested, but not proven, by one previous investigation in allo-SCT. 7 The association with alemtuzumab (known to increase CMV reactivation after allo-SCT 27 ) prompted us to investigate the role of CMV reactivation.…”

“…One candidate would be EBV; others have not found an association between EBV and paraproteinaemia. 5,14,22 However, Drouet et al found that co-infection with both CMV and EBV was required for an association with paraproteinaemia in renal transplant patients, 16 and EBV lymphoproliferation has been associated with paraproteinaemia in children following allo-SCT. 4 We did not routinely monitor EBV levels and so cannot test whether an association exists in our patient cohort.…”