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Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC but only low avidity to donor-MHC after allogeneic bone marrow transplantation.

In the thymus maturing T lymphocytes are positively selected for efficient interaction with self-MHC molecules. Consequently, mature peripheral T cells recognize foreign (microbial) antigens in association with self-MHC molecules (known as MHC restricted recognition). In experimental bone marrow transplantation (BMT) lymphohaemopoietic stem cells from an MHC disparate donor transfused to an irradiated host give rise to mature T lymphocytes with host-MHC restriction specificity. While experiments with T cell receptor transgenic mice have largely confirmed this concept, many studies using genetically unmanipulated animals analysing polyclonal T cell repertoires have also shown donor-MHC restricted T cell activities after allogeneic BMT. To analyse this discrepancy we generated 18 virus specific cytotoxic T cell (CTL) clones, 16 from F1 into parent and two from fully allogeneic bone marrow chimeras, and analysed the MHC restriction specificity in proliferation and cytotoxicity assays. The cytotoxicity of all the clones was primarily host-MHC restricted. However, the CTL clones proliferated to viral antigen presented by both donor- or host-MHC. Our model allowed CTL cloning by cross-specific stimulation with antigen plus either donor-MHC or else host-MHC. Interestingly, even the 14 CTL clones which had been raised with donor-MHC systematically killed host-MHC but not donor-MHC expressing cells. Thus, after BMT, CTLs may proliferate crossreactively to donor-MHC but cytolysis is predominantly directed to host-MHC expressing cells. Since lytic CTL activity probably reflects high avidity CTL interaction necessary for viral clearance in vivo, the data suggest that the donor-MHC restricted CTL activity may not be protective and that virus may escape CTL surveillance in donor cells.

Animals↗

The AVID trial: evidence based or randomized control trials--is the AVID study too late? Antiarrhythmics Versus Implantable Defibrillators.

A great body of clinical evidence has been accumulated--before and without the AVID trial--showing that implantable defibrillators prolong life better than currently available antiarrhythmic drugs. With this evidence already available, we question the validity of a trial that attempted, in effect, to place a price tag on life and quality of life.

Anti-Arrhythmia Agents↗

Regulation of alpha 4 integrin avidity in human B cells: requirement for dephosphorylation events for high avidity VCAM-1 binding.

The authors compared the phosphorylation-dependent signal transduction pathways involved in the regulation of adhesiveness of integrin LFA-1 with that of alpha 4 integrins binding to VCAM-1. The authors developed an in vitro method to monitor changes in adhesiveness using a VCAM-1 fusion protein coupled to magnetic beads. For LFA-1, a similar method has previously been established using an ICAM-1 fusion protein. Binding of cells was monitored and found to be strictly integrin alpha 4 and VCAM-1 dependent. The serine/threonine phosphatase inhibitors okadaic acid and calyculin A were equally potent in inhibiting binding to VCAM-1 as to ICAM-1, and inhibition of protein phosphatase-1 (PP1) is proposed to be the important denominator. Similarly, the phorbol ester PDBu, potentially stimulating protein phosphatase-1 and staurosporine, an inhibitor of serine/threonine kinases, enhanced adhesion to VCAM-1 as has previously been shown for ICAM-1. A major difference was that a significant portion of the binding to VCAM-1 was not susceptible to inhibition by drugs while binding to ICAM-1 could be completely inhibited. We propose that the adhesiveness of the alpha 4 integrins for VCAM-1 and of LFA-1 for ICAM-1 is regulated by similar or identical protein kinases and phosphatases.

B-Lymphocytes↗

Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines. The Vaccine Study Group.

OBJECTIVE: Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen. In this study, we compared the avidity of antibodies elicited by vaccination with three Haemophilus influenzae type b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity. DESIGN: A convenience sample of 171 postvaccination serum samples with more than 0.5 microgram/mL of anticapsular antibody, the minimum concentration required for measurement of avidity. The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM197 (Oligo-CRM). PATIENTS: Healthy infants recruited in private practices. PRIMARY OUTCOME MEASURES: Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers. RESULTS: In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (P less than .001). The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (P less than .02) but higher than PRP-OMPC (P = .001). Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (P less than .001). Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM-1 or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM-1 or less. Antibodies with avidity of 1.25 nM-1 or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM-1 or greater (P less than .001). CONCLUSIONS: Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays. Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease.

Antibodies, Bacterial↗

Molecular mechanisms and biological significance of CTL avidity.

CD8 CTLs are a major effector for protection against cancer as well as many infectious diseases, including HIV/AIDS. CD8 CTL recognize antigenic peptides in the context of class I MHC. CTL functional avidity has been shown to be an important determinant of in vivo efficacy. CTL that can recognize peptide/MHC only at high antigen density are termed low avidity CTL, while those that can recognize their cognate antigen at low densities are termed high avidity CTL. Recent studies have demonstrated that high avidity CTLs are essential for the effective clearance of viral infections and for the elimination of tumor cells. At this time, approaches that can target high avidity cells for expansion in vivo are not well defined; however, new insights are beginning to emerge. A recent study has shown that prime-boost immunization may be an effective method to generate high avidity CTLs that recognize HIV antigens. In addition, we recently found that high levels of costimulation (signal 2) can skew the CTL response toward higher avidity cells. Thus, vectors expressing a triad of costimulatory molecules (TRICOM) or dendritic cells expressing higher levels of costimulatory molecules, can be used to induce high avidity CTL. Finally a critical role for CD4+ T cell help in the generation of high avidity cells has recently been identified (Palmer, manuscript submitted). While high avidity CTLs are superior for viral and tumor clearance, they also have a greater sensitivity to antigen induced cell death. In some types of chronic infections, such as HIV and HCV, as well as in cancer, the host may lose, by clonal exhaustion or other apoptotic mechanisms, the effector cells that are most critical to viral or tumor clearance. In this review, we examine the current knowledge concerning CTL avidity. We discuss the factors that may distinguish high avidity CTLs from low avidity CTLs and describe some of the mechanisms these cells use to clear viral infections. In addition, we study possible immunization strategies that may be used to elicit higher avidity CTLs and describe what is known about the factors that render these cells more susceptible to apoptosis than low avidity CTLs. Finally, we will incorporate these various elements into a general discussion of possible approaches for induction and maintenance of an effective immune response that can result in clearance of tumors or chronic viral infections and the relevance to vaccine development.

Cytotoxicity, Immunologic↗

Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.

We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.

Adolescent↗

Use of immunoglobulin G antibody avidity for differentiation of primary human herpesvirus 6 and 7 infections.

A human herpesvirus 7 (HHV-7) indirect immunofluorescence antibody avidity test was developed and used with an existing human herpesvirus 6 (HHV-6) antibody avidity test to detect and distinguish low-avidity antibodies to HHV-6 and HHV-7 and hence the respective primary infections. With sera from 269 British children aged 0 to 179 weeks, the tests showed that most (10 of 98 serum samples [13%]) HHV-6 low-avidity antibody was found in the first year of life, whereas for HHV-7, most (18 of 101 serum samples [20%]) HHV-7 low-avidity antibody was found in the second year of life. Five children had low-avidity antibodies to both viruses. Of nine Japanese children with previously serologically proven primary HHV-6 or HHV-7 infections, eight had low-avidity antibody only to the relevant virus, but one child had low-avidity antibodies to HHV-6 and HHV-7. The avidity tests were applied to five British children and further proof of viral infection was sought by the detection of specific DNA in serum or plasma, and saliva or cerebrospinal fluid. In two children who had low-avidity antibody to HHV-7 but who were seronegative for HHV-6, only HHV-7 was found. Both viruses were detected in one child with low-avidity HHV-7 antibody and high-avidity HHV-6 antibody. In two children with low-avidity antibodies to both viruses, HHV-6 and HHV-7 DNAs were found, confirming dual primary infections and excluding antibody cross-reactivity.

Adult↗

A novel CD8-independent high-avidity cytotoxic T-lymphocyte response directed against an epitope in the phosphoprotein of the paramyxovirus simian virus 5.

Adoptive transfer studies have shown that cytotoxic T lymphocytes (CTL) of high avidity, capable of recognizing low levels of peptide-MHC I molecules, are more efficient at reducing viral titers than are low-avidity CTL, thus establishing CTL avidity as a critical parameter for the ability of a CTL to clear virus in vivo. It has been well documented that CTL of high avidity are relatively CD8 independent, whereas low-avidity CTL require CD8 engagement in order to become activated. In this study we have analyzed the antiviral CTL response elicited following infection with the paramyxovirus simian virus 5 (SV5). We have identified the immunodominant and subdominant CTL responses and subsequently assessed the avidity of these responses by their CD8 dependence. This is the first study in which the relationship between immunodominance and CTL avidity has been investigated. The immunodominant response was directed against an epitope present in the viral M protein, and subdominant responses were directed against epitopes present in the P, F, and HN proteins. Similarly to other CTL responses we have analyzed, the immunodominant response and the subdominant F and HN responses were comprised of both high- and low-avidity CTL. However, the subdominant response directed against the epitope present in the P protein is novel, as it is exclusively high avidity. This high-avidity response is independent of both the route of infection and expression by recombinant SV5. A further understanding of the inherent properties of P that elicit only high-avidity CTL may allow for the design of more efficacious vaccine vectors that preferentially elicit high-avidity CTL in vivo.

Animals↗

Measurement of avidity of specific IgG for verification of recent primary rubella.

Sixty-four subjects' serum samples, positive or equivocal by rubella IgM assays and containing rubella IgG, were examined for the avidity of rubella IgG. Four of the sera originated from rubella reinfections; others had false-positive IgM results due to interference by parvovirus infection or by other mechanisms; and the remaining were sera from the acute phase or convalescence of primary rubella. A novel IgG avidity test, avidity-ELISA, and a semiquantitative haemolysis typing assay were used. According to the avidity-ELISA, 29 subjects had recent primary rubella (low IgG avidity), and another 29 had previous rubella immunity (high IgG avidity), whereas 6 serum samples gave borderline avidity values. Comparison of these results with pre-existing clinical records and laboratory data showed that all samples with low IgG avidity were obtained during or shortly after acute primary rubella. All sera with high IgG avidity originated from the previously immune subjects; the rubella reinfections were confined within this group. Five of the six sera with borderline avidity values were obtained within 2 months from primary rubella. In conclusion, the measurement of IgG avidity is a powerful tool for the distinction of acute or recent primary rubella from pre-existing rubella immunity, including rubella reinfections.

Adult↗

Avidities of IgG directed against viral capsid antigen or early antigen: useful markers for significant Epstein-Barr virus serology.

Classical Epstein-Barr virus (EBV) serology can be misleading in some cases due to the variability of the viral capsid antigen (VCA)-IgM response, persistent or reactivated VCA-IgM, or loss of anti-EBNA-1 during suppression of the cellular immune system. Therefore, we studied the usefulness and significance of avidity determinations of VCA-IgG and EA-IgG to achieve unequivocal interpretation of serological results. Avidities of EBV capsid antigen-specific IgG (VCA-IgG) and early antigen-specific IgG (EA-IgG) were determined by indirect immunofluorescence during and after acute EBV infection. Low-avidity antibodies were removed from antigen-antibody complexes by incubation with 6 M urea for 3 minutes. The analysis of 105 sera taken at defined time spans with regard to the onset of clinical symptoms allowed us to determine the kinetics of maturation of avidity of VCA-IgG. All sera had low-avidity antibodies at the onset of disease. More than 90% of the sera showed an avidity index below 0.25 during the first 10 days after the onset of disease. Fifty percent of the sera exhibited an avidity index of 0.25 or above 20-30 days after the onset of clinical symptoms. Sera from past infections uniformly exhibited avidity indices of 0.5 or 1. Avidity of EA-IgG may still be low when avidity of VCA-IgG is already borderline or high, thus allowing further differentiation of acute and recent infections. Avidity determination represents an important additional marker of serology in classical cases and allows diagnosis in aberrant cases, such as acute infections with low or undetectable VCA-IgM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Rheumatoid factor avidity in patients with rheumatoid arthritis: identification of pathogenic RFs which correlate with disease parameters and with the gal(0) glycoform of IgG.

The standard ELISA for measuring rheumatoid factor (RF) binding was modified by treatment after the RF-Fc interaction with 2 M guanidine, which allowed a measurement of the avidity of the interaction. Incubation with 4 M guanidine eliminated RF binding. There was a direct correlation (r = 0.99) between the avidity as measured by the modified guanidine ELISA, and the dissociation constant for monoclonal RFs, as measured by competitive ELISA. Of the seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs (> or = 8% RF binding remaining after guanidine treatment). Tender joint count scores were significantly higher in the high avidity group (p = 0.05), whereas there was no significant difference in the ages, disease duration, sedimentation rate, RF titer or serum Ig levels compared to those with low-avidity RFs. Additionally 58% of those with high-avidity RFs had subcutaneous nodules, compared to 40% of the low-avidity group. A significantly higher number of nodules was present in the high-avidity RF group compared to those with low-avidity RFs (p = 0.03). Interestingly, the RF avidity was significantly higher in isolated immune complexes (IC), compared to that in circulating IgM RFs (p = 0.01). The RF avidity correlated with the presence of the glycoform of IgG lacking galactose in both circulating and IC-derived IgG (p = 0.003 and 0.009 respectively). Information about the strength of binding to Fc identifies a subgroup of IgM RFs that are likely pathological in patients with RA, as well as a specific glycoform of the target antigen.

Antibodies↗

Maternal herpes simplex virus antibody avidity and risk of neonatal herpes.

OBJECTIVE: The objective of the study was to assess whether herpes simplex virus antibody avidity is associated with risk of transmission of herpes simplex virus to the neonate. STUDY DESIGN: We developed a novel herpes simplex virus type 1 avidity test based on the commercially available Focus HerpeSelect-1 enzyme-linked immunosorbent assay kit using sera from nonpregnant subjects with genital herpes simplex virus-1 infection. We used this test, and the previously developed herpes simplex virus type 2 avidity test, to compare maternal herpes simplex virus-1 and herpes simplex virus-2 antibody avidity in women who transmitted herpes simplex virus to the neonate and women who had herpes simplex virus isolated from genital secretions at delivery but who did not transmit herpes simplex virus to their infants. RESULTS: Among nonpregnant subjects with genital herpes simplex virus-1 infection whose sera were used to develop the herpes simplex virus-1 avidity test, a significant relationship between herpes simplex virus-1 antibody avidity and time since herpes simplex virus-1 acquisition was observed (P < .001, mixed-effects model), with median avidity values increasing over time after primary infection. Among pregnant, herpes simplex virus-1, or herpes simplex virus-2 seropositive women, 4 of 8 women (50%) with avidity 40 or greater transmitted herpes simplex virus to the neonate, compared with only 12 of 97 (12%) of women with avidity greater than 40 (P = .02). CONCLUSIONS: Herpes simplex virus-1 antibody avidity increased over time after genital herpes simplex virus-1 acquisition, as has been previously observed for herpes simplex virus-2. Among women with herpes simplex virus antibody at delivery, low antibody avidity was associated with herpes simplex virus transmission to the neonate and may be a useful marker for recent seroconversion.

Adult↗

High avidity CD8+ T cells generated from CD28-deficient or wildtype mice exhibit a differential dependence on lipid raft integrity for activation.

CD28 has been shown to play an important role in T cell activation. Among the downstream events associated with CD28 engagement is the reorganization of the cytoskeleton resulting in lipid raft aggregation. In our previous studies we investigated the involvement of lipid rafts in the activation of high avidity CD8+ T lymphocytes, which recognize cells bearing very low levels of peptide antigen, versus low avidity cells, which require high levels of peptide antigen. In these studies we found that high avidity cells were much more sensitive to lipid raft disruption compared to low avidity cells. Given the important role for CD28 in lipid raft reorganization and our previous finding that high avidity cells are extremely dependent on lipid raft integrity, we hypothesized that high avidity cells could not be generated in the absence of CD28. Surprisingly, we have found that the absence of CD28 does not alter the ability to generate high or low avidity CD8+ T cells. In fact high and low avidity lines generated in parallel from CD28-deficient and WT mice exhibited very similar requirements for peptide antigen. We next compared the effect of lipid raft disruption on the activation of high versus low avidity cells from CD28-deficient and WT mice. While high avidity cells generated from WT mice exhibited the expected dependence on lipid raft integrity, high avidity cells from CD28-deficient mice were not affected. These data suggest that the lines generated from the CD28-deficient mice have developed alternative strategies to promote high sensitivity to peptide antigen.

Animals↗

Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1.

We have evaluated solid-phase ELISA IgG antibody avidity studies as a means of identifying cases of recent HIV-1 infection. Although separate studies on the avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been reported, a comparison of the ability of patients to simultaneously mature their immune response to more than one HIV antigen immediately following seroconversion appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity which reflects the time since seroconversion in all cases. In contrast, however, only some patients produced high-avidity anti-p24 or anti-p17 antibodies during the same time span. While the avidity of anti-gp41 antibodies remained high in cases of non-recent HIV infection, even in the face of advanced disease, we have confirmed the findings of others that the avidity of anti-p24 falls before the onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could reliably be of value in identifying cases of recent HIV infection, the avidity of anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti-gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained high. In contrast, anti-p24 titres fell, even during the early followup period in some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better predictor of disease progression in 'remote' cases than anti-p24 titre. The avidity and titres of these antibodies are presented in relation to the clinical details, p24 antigen status, CD4 and CD8 counts where these are known.

Adult↗

The avidity of allospecific cytotoxic T lymphocytes (CTL) determines their cytokine production profile.

Donor-specific CTL present within the cardiac allograft during a rejection episode are distinct from those that populate the cardiac allograft in the absence of rejection. Whereas the former generally have a high avidity for donor cells, the latter mainly have a low avidity for donor cells. This observation made us reason that high-avidity CTL are implicated in transplant rejection, whereas low-avidity CTL are not. In the present study, we analyse whether both CTL subsets were distinct with respect to their IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) secretion pattern. CTL clones with either a high or a low avidity for donor antigens were stimulated with donor cells, third party cells, or immobilized anti-CD3 MoAb and the amount of cytokine released was measured. High- and low-avidity CTL clones were found to differ with respect to their IFN-gamma production profile. Stimulation with donor cells resulted in IFN-gamma secretion by high-avidity CTL clones, but not by low-avidity CTL clones. CD3 stimulation, in contrast, led to secretion of equivalent amounts of IFN-gamma by both CTL subsets. These observations indicate that low-avidity CTL are fully capable of producing IFN-gamma, but, in contrast to high avidity CTL, fail to do so when they encounter donor cells. As IFN-gamma favours the occurrence of transplant rejection, this observation emphasizes the relevance of high-avidity CTL in the rejection process. Additionally, the data show that the cytokine production profile of CTL depends on the nature of the stimulus.

Antibodies, Monoclonal↗

Changes in avidity and level of immunoglobulin G antibodies to Mycobacterium tuberculosis in sera of patients undergoing treatment for pulmonary tuberculosis.

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.

Antibodies, Bacterial↗

Immunoglobulin G avidity in diagnosis of toxoplasmic lymphadenopathy and ocular toxoplasmosis.

Traditional serological techniques have some limitations in evaluating the duration of Toxoplasma gondii infection in pregnant women, patients with lymphadenopathy, and older children suspected of having congenital toxoplasmosis. In these three groups of patients, two variants of T. gondii immunoglobulin G (IgG) avidity tests were used: an EIA Kit (Labsystems) and a noncommercial enzyme-linked immunosorbent assay specially elaborated in the laboratory. The avidity of specific IgG in sera from 23 patients with a known recently acquired infection (mainly pregnant women) was low (less than 30%), whereas that in sera from 19 patients with toxoplasmic lymphadenopathy of 3 weeks to 6 months in duration (mean, 8.3 weeks) covered a large range (between 0.2 and 57.8%; mean, 25. 7%); high avidity results were observed for 10 of 19 patients (52. 6%). The large range of IgG avidity in patients with toxoplasmic lymphadenopathy suggests various durations of infection in these patients, with a tendency for a chronic phase of toxoplasmosis. According to the avidity marker, five patients with lymphadenopathy for less than 3 months did not have a recent Toxoplasma infection. In 6 of 19 patients with lymphadenopathy (31.6%), low IgG avidity values persisted until 5 months after the first serological examination. In all four patients with a documented chronic course of Toxoplasma infection (6 months to 8 years after the first positive serology), high IgG avidity values were observed. Among sera from 10 children and young immunocompetent adults suspected of having ocular reactivation of congenital toxoplasmosis, all had high IgG avidity values (over 40%), suggesting congenitally acquired ocular infection rather than noncongenital infection. In conclusion, the avidity of IgG is a valuable marker of recent toxoplasmosis in pregnant women, suggests the duration of invasion in patients with lymphadenopathy, and may be helpful for differentiation between reactivation of congenital infection and recently acquired ocular toxoplasmosis in immunocompetent patients. A low IgG avidity does not always identify a recent case of toxoplasmosis, but a high IgG avidity can exclude primary infections of less than 5 months' duration.

Adult↗