Age‐related patterns of cytomegalovirus antibodies accompanying Epstein‐Barr virus co‐infection

An investigation was performed to address the need to establish the rate of positive heterophil antibody responses, oropharyngeal isolation of Epstein-Barr virus (EBV), and the evolving pattern of EBV-specific antibody responses among children with documented EBV-infectious mononucleosis. Findings showed that the rate of heterophil antibody responses appeared to increase progressively with advancing age from infancy up to 4 years, after which the rates approached values similar to that reported in young adult patients. The rapid slide test detected a heterophil antibody response as frequently as the Paul-Bunnell-Davidsohn horse cell test, except in children less than 4 years old. The decreased sensitivity found with the rapid slide test in the very young was associated with their less intense heterophil response. The younger group of children also developed a lower acute mean titer and, as a result, a decreased persistence of immunoglobulin M antibody to EBV-capsid antigen, whereas they had more frequent responses to EBV-early antigen directed to restricted component than both the older subjects and adults reported elsewhere. Antibodies to EBV-nuclear antigen, characteristically a late-onset antibody, tended to develop earlier than noted in adult patients. In contrast, the prevalence and continued excretion of EBV from oropharyngeal secretions was similar to that reported in adult patients. It is speculated that these age-related differences in host responses are associated with the ontogeny of the immunologic system.

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Immunohistochemical Expression Pattern of Germinal Center and Non-Germinal Center Markers in Age-Related Epstein Barr Virus-Associated B-Cell Lymphoproliferative Disorder

Blood ◽

10.1182/blood.v112.11.5289.5289 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5289-5289

Author(s):

Domingo Morales ◽

Brady Beltran ◽

Luis Riva ◽

Fernando Hurtado ◽

Renzo Salas ◽

...

Keyword(s):

B Cell ◽

Germinal Center ◽

Epstein Barr Virus ◽

Progressive Disease ◽

Cell Lymphoma ◽

Immunohistochemical Expression ◽

Chop Regimen ◽

Barr Virus ◽

Age Related ◽

Epstein Barr

Abstract BACKGROUND: Age-related Epstein Barr virus (EBV)-associated B-cell lymphoproliferative disorder (LPD) is a newly described entity initially reported in Japanese patients with diffuse large B-cell lymphoma (DLBCL) and coinfection with EBV. It usually affects elderly patients and is characterized by poor survival. Immunohistochemical analysis of patients with DLBCL using bcl-6, CD10 and MUM1 can further subclassify DLBCL in germinal center (GC)-like or non-germinal center (non-GC) phenotypes. Non-GC phenotypes have been associated with resistance to conventional therapy and poorer prognosis when compared to GC-like phenotypes, even in the rituximab era. AIM: The goal of this study was to evaluate the immunohistochemical pattern of GC and non-GC markers in patients with diagnosis of age-related EBV-associated B-cell LPD. PATIENTS AND METHODS: Between January 2002 and June 2008, twelve patients with age-related EBV-associated B-cell LPD were identified and included in the analysis. Clinical data were reviewed retrospectively and patient’s biopsies were analyzed for the immunohistochemical expression of bcl-6, CD10, CD30 and MUM-1/IRF4 by tissue microarray technique. Cases were also investigated for EBV-encoded RNA (EBER) using an in-situ hybridization technique. RESULTS: In this cohort, the mean age was 72 years old (range 34–85) at diagnosis; the male to female ratio was 1.4. B symptoms occurred in 5 out of 10 patients. ECOG performance status was higher than 1 in 9 of 10 patients. Advanced stages (III/IV) were observed in 8 of 10 patients. IPI score was higher than 2 in 8 of 10 patients. Extranodal involvement was identified in pleura (n=2), suprarenal gland (n=1), stomach (n=1), cecum (n=1) and bone marrow (n=1). Morphology in all cases was consistent with large cell lymphoma. All cases were positive for EBER and CD20 expression. Two cases had strong positivity to CD30. Ten cases (83%) had non-GC phenotype and 2 cases (17%) had GC-like phenotype. From the non-CG group, five patients (50%) received CHOP regimen. Two had complete response and three had progressive disease. Most of the cases died during the first year with the exception of two patients; one patient had a survival of 42 months and the other is currently receiving treatment with CHOP. From GC-like phenotype group, one patient received CHOP regimen with progressive disease and died 3 month after diagnosis. The other case was lost to follow-up. CONCLUSION: The majority of patients in this report who were diagnosed with the newly described age-related EBV-associated B-cell LPD had a non-GC immunophenotype. This distinct subtype of DLBCL presents with advance stages, high IPI scores, extranodal involvement and short survival. Further research is necessary to elucidate the lymphomagenetic role and the prognostic value of EBV and to improve therapies, which are highly needed in this group of LPD.

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Age-related Epstein-Barr virus (EBV)–associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients

Blood ◽

10.1182/blood-2008-06-164806 ◽

2009 ◽

Vol 113 (12) ◽

pp. 2629-2636 ◽

Cited By ~ 113

Author(s):

Naoko Asano ◽

Kazuhito Yamamoto ◽

Jun-Ichi Tamaru ◽

Takashi Oyama ◽

Fumihiro Ishida ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Epstein Barr Virus ◽

Age At Onset ◽

B Cell Lymphoma ◽

Female Ratio ◽

Barr Virus ◽

Age Related ◽

Classic Hodgkin Lymphoma ◽

Epstein Barr

Abstract Age-related Epstein-Barr virus–associated B-cell lymphoproliferative disorder (aEBVLPD) is a disease group characterized by EBV-associated large B-cell lymphoma in elderly without predisposing immunodeficiency. In nearly one- third of cases, aEBVLPD occurs as a polymorphous subtype with reactive cell-rich components, bearing a morphologic similarity to classic Hodgkin lymphoma (cHL). The aim of this study was to clarify clinicopathologic differences between the polymorphic subtype of aEBVLPD (n = 34) and EBV+ cHL (n = 108) in patients aged 50 years or older. Results showed that aEBVLPD was more closely associated with aggressive clinical parameters than cHL, with a higher age at onset (71 vs 63 years); lower male predominance (male-female ratio, 1.4 vs 3.3); and a higher rate of involvement of the skin (18% vs 2%), gastrointestinal tract (15% vs 4%), and lung (12% vs 2%). aEBVLPD was histopathologically characterized by a higher ratio of geographic necrosis, greater increase (> 30%) in cytotoxic T cells among background lymphocytes, higher positivity for CD20 and EBNA2, and absence of CD15 expression. As predicted by the clinical profile, aEBVLPD had a significantly poorer prognosis than EBV+ cHL (P < .001). The polymorphous subtype of aEBVLPD constitutes an aggressive group with an immune response distinct from EBV+ cHL, and requires the development of innovative therapeutic strategies.

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Epstein-Barr Virus Infection in an Elderly Nonimmunocompromised Adult Successfully Treated with Rituximab

Case Reports in Hematology ◽

10.1155/2014/641483 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4

Author(s):

Jacob P. Smeltzer ◽

Matthew T. Howard ◽

Wilson I. Gonsalves ◽

Thomas E. Witzig

Keyword(s):

Epstein Barr Virus ◽

The Elderly ◽

Lymph Node Biopsy ◽

Epstein Barr Virus Infection ◽

Diagnostic Challenge ◽

Barr Virus ◽

Age Related ◽

Epstein Barr ◽

Barr Virus Infection ◽

Systemic Symptoms

Epstein-Barr virus (EBV) is a ubiquitous virus that commonly affects children and adolescents. In addition to causing a viral illness, it is also associated with various malignancies in particular B cell lymphomas and lymphoproliferative disorders. Differentiating between the two processes can be a diagnostic challenge. Here, we present a case of an atypical EBV infection in an elderly patient with severe systemic symptoms, multiorgan involvement, lymphadenopathy, and negative EBV serology. Excisional lymph node biopsy demonstrated features of a lymphoproliferative process involving EBV. Despite supportive care, she experienced continued clinical deterioration and was successfully treated with rituximab. This case illustrates the diagnostic challenges of these cases particularly in the elderly who may have age related immunosenescence, the utility of EBV PCR testing, and the clinical efficacy of rituximab in clearing the infected cells.

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Age-related restriction of the light chain heterogeneity of anti-IgG antibodies induced by Epstein-Barr virus stimulation of human lymphocytes in vitro

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(81)90127-6 ◽

1981 ◽

Vol 18 (3) ◽

pp. 344-350 ◽

Cited By ~ 4

Author(s):

Sherman Fong ◽

Jean-Louis Pasquali ◽

Constantine D. Tsoukas ◽

John H. Vaughan ◽

Dennis A. Carson

Keyword(s):

Light Chain ◽

Epstein Barr Virus ◽

Human Lymphocytes ◽

Igg Antibodies ◽

Barr Virus ◽

Age Related ◽

Epstein Barr ◽

Stimulation Of

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Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract

Cancers ◽

10.3390/cancers13153815 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3815

Author(s):

Eri Ishikawa ◽

Akira Satou ◽

Masanao Nakamura ◽

Shigeo Nakamura ◽

Mitsuhiro Fujishiro

Keyword(s):

B Cell ◽

Lymphoproliferative Disorder ◽

Epstein Barr Virus ◽

B Cell Lymphoma ◽

Biological Behavior ◽

Routine Practice ◽

Gi Tract ◽

Barr Virus ◽

Age Related ◽

Epstein Barr

Epstein-Barr virus positive B-cell lymphoproliferative disorder (EBV+ B-LPD) encompasses a broad clinicopathological spectrum and distinct clinical behavior that relatively favors the gastrointestinal (GI) tract. In this review, we provide an update on the clinicopathological features and biological behavior of EBV-positive mucocutaneous ulcer (EBVMCU) and primary EBV+ diffuse large B-cell lymphoma (DLBCL) of the GI tract. EBVMCU is a newly recognized entity but well known as an indolent and self-limited EBV+ B-LPD occurring in various immunodeficiencies. In contrast, EBV+ DLBCL constitutes the largest group of EBV+ B-LPDs and is regarded as an aggressive neoplasm. These two distinct diseases have historically been distinguished in the reappraisal of age-related EBV-associated B-LPDs but are challenging in routine practice regarding their differential diagnostic and therapeutic approaches. An increasing number of reports indicate that they are epidemiologically prevalent beyond western and eastern countries, but their comprehensive analysis is still limited. We also describe the PD-L1 positivity of tumorous large cells and non-malignant immune cells, which is relevant for the prognostic delineation among patients with primary DLBCL of the GI tract with and without EBV on tumor cells.

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