Behaviour of IgG Antibody Avidity for the Antigen and of IgA Antibody in Active Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus and Human Herpes Virus 6 Infections, Adaptation of a Commercial Test

During infection by herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6), IgM antibody (Ab) are not sufficiently consistent for use in the diagnosis of primary infection, reinfection or reactivation, whether symptomatic or not. These Abs can give false-negative results, because they are produced in small quantities which are difficult to detect or not produced. 1 False-positive results can be due to their long persistence and their presence in processes unrelated to the actual infection; 2 positive findings may derive from reactivation or from reinfection, 36 as also observed in patients infected with the human immunodeficiency virus (HIV). Common epitopes in viruses, e.g. HSV and varicella zoster virus (VZV) may lead to simultaneous laboratory detection of various IgMs. Finally there are heterotypical reactions between circulating Abs and white blood cells, the main target cells for CMV, EBV and HHV-6. 7'8 The diagnosis of active herpes virus infection by the detection of a four-fold increase in the IgG titre is difficult. The titre rise may be failed, as IgGs usually appear very soon after the onset of symptoms. 9 In this context, the study of Abs of the IgA and IgG classes with low avidity for the antigen could constitute a good marker for recent primary infection. IgA Abs are present in primary infection, they appear later than IgM Abs, and they are found in reactivation. Quantification * Address correspondence to: Dr J. Guti6rrez. C/Camino Bajo de Huetor 84, l-A, E-18008 Granada, Spain. Accepted for publication 4 November 1996. of specific IgG Abs avidity by simple techniques is a new sensitive and specific method for the serological diagnosis and follow-up of certain infections. 3'4 This method could be used to determine the approximate point of the primary infection and to distinguish between reactivation, reinfection and primary infection. Generally, the affinity of IgG for the antigen is low after the first antigen contact and rises during the following weeks and months due to maturation of the B lymphocytes and the decrease in antigen stimulus. For this reason we set out to determine the clinical value of the study of IgA and specific IgG avidity for the detection of active disease and primary infection, respectively, caused by the herpes viruses CMV, EBV, HSV and HHV-6. Materials and Methods Serum samples from patients and healthy subjects with past infection were analysed in order to study specific IgG avidity and to detect IgA to CMV, EBV, HSV and HHV-6. IgA were not studied in samples from healthy subjects with a past HHV-6 infection. The samples studied and their clustering into panels are shown in Table I. The samples from patients were analysed retrospectively, after being taken 15-25 days following the onset of clinical symptoms, at intervals of 20-25 days where various samples w