EBNA1 expression in a lung transplant recipient with hypocomplementemic urticarial vasculitis syndrome

Abstract

This article describes a transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome who expressed persistently Epstein-Barr virus nuclear antigen 1 (EBNA1) in peripheral blood. The patient received a bilateral lung transplant and was subsequently followed with monitoring of EBV expression in peripheral blood. Evaluation of viral expression in peripheral blood, serum, and graft tissue was performed with RT-PCR, Q-PCR, indirect immunofluorescence, anti-peptide assays, and in situ hybridization; samples were collected at various time-points up to 91 days post-transplantation. The patient expressed EBNA1 in 8/10 (80%) of the peripheral blood samples tested during the post-transplantation period, and interestingly, even including the day of transplantation. After analyses of indicative EBV mRNA, EBNA1 expression was found mainly to be Qp-initiated EBNA1, known to be important for EBV maintenance. Anti-EBNA1 epitope mapping showed significantly higher and broader antibody responses to EBNA1 epitopes pre-transplantation when compared to normal controls and a matched lung transplant control. Post-transplantation this response was largely diminished but there were still epitopes significantly higher than controls. Our results show the presence of EBV-positive proliferating cells before onset of intensive immunosuppressive treatment. Although no previous connection between EBV and hypocomplementemic urticarial vasculitis syndrome has been reported, it is tempting to speculate that the continuous EBNA1 expression is not caused by immunosuppression or post-transplant lymphoproliferative disease, but may be a factor involved in the etiology of the autoimmune disease.

Infectious Serologies and Autoantibodies in Wegener's Granulomatosis and Other Vasculitides

“…EBV has been linked to numerous vasculitides, including Kawasaki disease, PAN, urticarial vasculitis, Henoch–Schonlein purpura, large‐vessel vasculitis, and Behçet disease 4,53–58 . However, no association between EBV and WG has been hitherto established, rendering our finding of increased serologic prevalence of IgG antibodies to EBV VCA and EBV early antigen in WG patients a novel one.…”

“…EBV has been linked to numerous vasculitides, including Kawasaki disease, PAN, urticarial vasculitis, Henoch-Schonlein purpura, large-vessel vasculitis, and Behçet disease. 4,[53][54][55][56][57][58] However, no association between EBV and WG has been hitherto established, rendering our finding of increased serologic prevalence of IgG antibodies to EBV VCA and EBV early antigen in WG patients a novel one. Theoretically, the true prevalence of EBV past infection may be underestimated as a result of decreased IgG production by peripheral blood mononuclear cells in response to in vitro stimulation with EBV, as has been demonstrated in blood samples from WG patients.…”

Comorbidity and pathogenic links of chronic spontaneous urticaria and systemic lupus erythematosus – a systematic review

“…Hypocomplementaemia can be found in 18–32% of UV patients and indicates a more severe disease . Rare hypocomplementemic urticarial vasculitis syndrome (HUVS) is considered to be an unusual type of SLE, SLE‐associated syndrome or an entirely separate entity . Histologically, UV is characterized by signs of leukocytoclastic vasculitis involving small veins in superficial layers of the skin .…”

Urticarial lesions: If not urticaria, what else? The differential diagnosis of urticaria

“…Among these, the most common are autoimmune connective tissue diseases (particularly SLE, 19,20,[48][49][50][51][52][53][54][55] but also systemic sclerosis, 56 GougeroteSjögren syndrome, 57 and paraneoplastic dermatomyositis 58 ), followed by infections (mainly chronic or acute viral hepatitis [59][60][61][62][63][64] and sporadic reports of EpsteineBarr virus, 65 Mycoplasma pneumoniae, 66 and Lyme disease 67 ) and inflammatory bowel diseases. 68 In some cases, UV can be a paraneoplastic manifestation, mainly associated with hematologic malignancies, including mostly non-Hodgkin B-cell lymphomas, 69-71 monoclonal gammopathies/myeloma, 72-74 anecdotal cases of Castleman disease, 75 and polycythemia rubra vera, 76 but also with various solid neoplasms (nonesmall cell lung cancer, 77 renal cancer, 78 testicular teratoma, 79 colon adenocarcinoma, 80 and nasopharyngeal carcinoma 58 ).…”