Cross-Reactivity of Epstein-Barr Virus-Specific Immunoglobulin M Antibodies with Cytomegalovirus Antigens Containing Glycine Homopolymers

Abstract

Timely and reliable detection of acute primary human cytomegalovirus (HCMV) infection is important in

Significant Liver Injury with Dual Positive IgM Antibody to Epstein-Barr Virus and Cytomegalovirus as a Puzzling Initial Manifestation of Infectious Mononucleosis

“…Both the elimination of CMV infection by a transient increase in IgM followed by persistent absence of IgG, and confirmation of EBV infection by seroconversion of IgG-EBNA, suggest the CMV-IgM test result was false positive. Glycine-alanine-rich elements in EBNA-1 protein (2, 13) and glycine-rich motifs within the non-structural CMV protein of pUL44 and pUL55 are widely used as diagnostic antigens (2). Since cross-reaction to major antigenic epitopes between these elements and motifs have been demonstrated to be a cause of false positive IgM-CMV results, it is tempting to speculate that induced EBV-IgM also recognized the CMV protein in the present case.…”

“…In addition, significantly elevated hepatic enzymes, over five-fold the normal range (8), and intra-abdominal lymphadenopathy (9) were not typical of IM. less frequently and in a milder form than in EBV-induced IM (3, 10), but these never become conclusive criteria for differentiation (2). A positive heterophile test certainly is a helpful clue for the identification of EBV-induced IM, but it cannot always be used because of its low prevalence in older (1) or in Japanese people (11).…”

“…Since cross-reaction to major antigenic epitopes between these elements and motifs have been demonstrated to be a cause of false positive IgM-CMV results, it is tempting to speculate that induced EBV-IgM also recognized the CMV protein in the present case. However, careful interpretation of this finding in combination with IgM-EBV, IgM-CMV, IgG-EBNA and IgG-CMV is essential for a diagnosis of a patient with IM symptoms (15), since IgM-CMV induced by CMV infection adversely cross-reacts with EBNA-1 protein (2,14). Inconsistent false positive rates of IgM-CMV in IM patients ranging from 20.4% (10) to 40.9% (15), depend probably upon the specificity of kits, i.e.…”

“…Difficulties of initial diagnosis of IM in older individuals have been documented because of the rare occurrence, absence of typical IM manifestations such as lymphadenopathy, tonsillopharyngitis, lymphocytosis accompanied by atypical lymphocytes and heterophile-antibody (1). On the other hand, other pathogenic microorganisms such as Toxoplasma or viruses such as cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and human immunodeficiency virus (HIV), also provoke heterophile antibody-negative IM-like symptoms (1,2). Further, it is also reported that EBV infection alters humoral immunity, i.e.…”

Rapid Etiologic Diagnosis of Herpes Virus Infections in Children

“…At present, virus isolation and serological tests are common methods for diagnosis of herpesvirus infections, although both of them are slow, labor-intensive, and inaccurate. Cross-reactivity can also impede the clinical application of immunological assays (9,10). Moreover, PCR method is limited to detect only one type of pathogens in spite of high sensitivity and specificity (11).…”