However, mothers infected before conception are also at risk of transmitting this disease to the fetus in the setting of immunodeficiency [26C29]. for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). Results Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14C199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95C13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41C242) and to (OR 2.91 for each OD unit increase, 95% CI 1.48C5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Conclusions Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of antibody. These measures could Cerdulatinib be clinically useful for predicting subsequent diseases in multiple at-risk populations. Keywords: toxoplasmic encephalitis, serological responses, Cerdulatinib predict, HIV, [1]. Exposure to is common in the general population, but the incidence of TE is low and the risk factors for it have been difficult to characterize. The most important risk factor for TE is immunosuppression, although some strains, and the residual burden of the parasite in the brain may also contribute to the risk of disease [2C4]. Elevated levels of antibody to the whole organism have also been associated with increased risk for TE [5C7]. The clinical signs and symptoms of TE are nonspecific; therefore, definitive diagnosis requires either a brain biopsy or unequivocal response to specific therapy. The poor predictive value of known risk factors for TE among matrix antigen 1 (MAG1) [8]. The level of MAG1 antibodies was highly correlated with the number of tissue cysts in the brain of infected mice and with signs of chronic infection, including lower body weight, behavioral changes, altered gene expression, and immune activation [9]. Herein we retrospectively identified samples that had been Cerdulatinib collected 2 years prior to the diagnosis of TE from seropositive people living with human immunodeficiency virus (HIV; PLWH) to evaluate the predictive value of serum antibodies to MAG1 and the whole organism for development of TE, alone or in combination. The choice of two years was intended to balance a reasonably long lead time before diagnosis and a clinically pertinent interval where therapeutic interventions, such as administration of anti-microbial prophylaxis, could be deployed. METHODS Study Population The study was a matched case-control design nested within the Multicenter AIDS Cohort Study (MACS), a prospective study of HIV/AIDS in men who have sex with men (MSM) in the United States, begun in 1984 [10, 11]. MACS recruited men from 4 US cities (Baltimore/Washington D.C.; Chicago, Illinois; Pittsburgh, Pennsylvania; Los Angeles, California) and had 4 enrollment cohorts: 1984C1985, 1987C1991, 2001C2003, and 2010C2018. MACS IL6R is a longitudinal study, where data and serum samples were collected at study entry and semiannual visits via interviewer-administered and computer-assisted questionnaires and physical examinations. Clinical outcomes were reported at the time of diagnosis by the attending physician. The present study is restricted to PLWH. Figure 1 is a flowchart showing case and control identification. There were 90 cases of TE reported in the MACS outcomes database between 1984 and 2002, diagnosed by clinical signs and symptoms, radiologic criteria for TE, or a self-report of TE. Cases were excluded if the diagnosis was based on self-report (n = 5), sera from recent HIV seroconverters (n = 9), or prediagnostic serum samples were not available (n = 11). After exclusions, 65 cases were screened for antibodies. seropositivity was an eligibility criterion because TE is the result of reactivation of a prior infection. Thirteen of the 65 cases were seronegative and were excluded from the study, leaving a total of 52 cases. Open in a separate window Figure 1. Flowchart to show case and control identification. Abbreviations: HIV, human immunodeficiency.