Sensitivity of undetectable level of high-sensitivity troponin T at presentation in a large non-ST-segment elevation myocardial infarction cohort of early presenters.

BACKGROUND: We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L. METHODS: All patients admitted to five centers in Sweden 2011-2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data. RESULTS: Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1-≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%-99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively. CONCLUSIONS: Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity.

HIV-1 neutralizing activity is correlated with increased levels of chemokines in saliva of HIV-1-exposed uninfected individuals.

AIM: Mucosal HIV-1 exposure stimulates a variety of mucosal immune responses, including IgA1-mediated virus neutralization, even in the absence of an established infection. We hypothesized that other immune molecules might also contribute to the HIV-1 neutralizing activity observed in the mucosal secretions of HIV-1 exposed uninfected individuals. METHODS: Saliva samples were collected from HIV-1 seronegative high-risk female sex workers (FSW) from Nairobi. Samples were also collected from HIV-1 IgG positive FSW and HIV-1 IgG negative low-risk women from the same geographical area. In all samples, IgA2, secretory leukocyte protease inhibitor (SLPI), regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha and beta (MIP-1alpha and -beta) and monocyte chemoattractant protein-1 (MCP-1) were quantified. The IgA1-depleted saliva samples were subsequently tested for neutralizing capacity in a PBMC-based neutralization assay using a primary HIV-1 clade A isolate to determine biological relevance of the measured molecules. RESULTS: HIV-1 specific neutralization was present in the IgA1-depleted fraction from saliva of both HIV-1 seropositive (9 of 10) and high-risk individuals (36 of 45) but not in HIV-1 IgG-negative control subjects (0 of 8). In the high-risk individuals, higher levels of CC-chemokines were seen in those that could neutralize HIV-1 as compared with those that could not (P<0.05). CONCLUSION: The HIV-1 neutralizing activity in saliva of HIV-1-exposed high-risk individuals is not only mediated by IgA1, but is also present in IgA1-depleted fractions and is associated with increased levels of CC-chemokines. Such innate immune factors may be important in limiting HIV-1 mucosal transmission.

HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers.

OBJECTIVES: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative (HEPS) individuals, but well controlled studies have not been performed. We performed a prospective, nested case-control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers (FSWs). DESIGN AND METHODS: A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan FSWs. After the completion of trial, FSWs who had acquired HIV (cases) were matched 1: 4 with persistently uninfected controls based on study arm, duration of HIV-seronegative follow-up, and time of cohort enrolment. Blinded investigators assayed the ability at enrolment of genital IgA to neutralize primary HIV isolates as well as systemic HIV-specific cellular IFNgamma-modified enzyme-linked immunospot and proliferative responses. RESULTS: The study cohort comprised 113 FSWs: 24 cases who acquired HIV and 89 matched controls. Genital HIV-neutralizing IgA was associated with reduced HIV acquisition (P = 0.003), as was HIV-specific proliferation (P = 0.002), and these associations were additive. HIV-specific IFNgamma production did not differ between case and control groups. In multivariable analysis, HIV-neutralizing IgA and HIV-specific proliferation each remained independently associated with lack of HIV acquisition. Genital herpes (HSV2) was associated with increased HIV risk and with reduced detection of HIV-neutralizing IgA. CONCLUSION: Genital HIV-neutralizing IgA and systemic HIV-specific proliferative responses, assayed by blinded investigators, were prospectively associated with HIV nonacquisition. The induction of these immune responses may be an important goal for HIV vaccines.