Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR–confirmed, SARS-CoV-2–hospitalized patients, as well as 464 healthy and non–COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non–COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD–binding antibodies exhibited neutralizing capacity, but only 74% of N-protein–positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein–binding antibodies does not always correlate with presence of S-RBD–neutralizing antibodies and caution against the extensive use of N-protein–based serology testing for determination of potential COVID-19 immunity.
Human mesenchymal stem cells (MSCs) express scavenger receptors that internalize lipids, including oxidized low-density lipoprotein (oxLDL). We report that MSCs phagocytoseMycobacterium tuberculosis(Mtb) through two types of scavenger receptors (SRs; MARCO and SR-B1), as blockade of the receptors with antibodies or siRNA knockdown decreased the uptake of Mtb. MSCs also expressed mannose receptor (MR) that was found to endocytose rhodamine-labeled mannosylated BSA (rMBSA), though the receptor was not involved in the uptake of Mtb. Dil-oxLDL and rMBSA taken up into MSC endosomes colocalized with Mtb phagosomes, thus suggesting that the latter were fusion competent. Phagocytosed Mtb did not replicate within MSCs, thus suggesting an intrinsic control of bacterial growth. Indeed, MSCs exhibited intrinsic autophagy, which was up-regulated after activation with rapamycin. SiRNA knockdown of autophagy initiator beclin-1 enhanced Mtb survival, whereas rapamycin-induced autophagy increased intracellular killing of Mtb. In addition, MSCs secreted nitric oxide after Mtb infection, and inhibition of NO by N(G)-monomethyl-L-arginine enhanced intracellular survival of Mtb. MSCs can be grown in large numbersin vitro, and autologous MSCs transfused into tuberculosis patients have been found to be safe and improve lung immunity. Thus, MSCs are novel phagocytic cells with a potential for immunotherapy in treating multidrug-resistant tuberculosis.
To estimate the accuracy of the protein/creatinine ratio in predicting 300 mg of protein in 24-hour urine collection in pregnant patients with suspected preeclampsia. Articles were identified through electronic databases (MEDLINE, CINHAL, and Cochrane) using the terms "preeclampsia," "protein/creatinine ratio," and "diagnosis," during the period January 1966 to October 2007. The relevant citations were hand searched. Included studies evaluated patients for suspected preeclampsia with a 24-hour urine sample and a protein/creatinine ratio. Only English-language articles were included. Studies including patients with only chronic illness such as chronic hypertension, diabetes mellitus, or renal impairment were excluded. Using the Quality Assessment of Diagnostic Accuracy Studies questionnaire, we created group 1 satisfying all the required criteria and group 2 not satisfying all of it. Two researchers independently extracted the accuracy data. A graph comparing six receiver operating characteristic curves was plotted. Twenty-one studies were identified, but only seven met our inclusion criteria (1,717 total patients). Group 1, with three studies, had 510 patients. The studies evaluated different cut points for positivity of protein/creatinine ratio from 130 mg/g to 700 mg/g. For protein/creatinine ratio 130-150 mg/g, sensitivity ranged from 90-99%, and specificity ranged from 33-65%; for protein/creatinine ratio 300 mg/g, sensitivity ranged from 81-98% and specificity ranged from 52-99%; for protein/creatinine ratio 600-700 mg/g, sensitivity ranged from 85-87%, and specificity ranged from 96-97%. Random protein/creatinine ratio determinations are helpful primarily when they are below 130-150 mg/g, in that 300 mg or more proteinuria is unlikely below this threshold. Midrange protein/creatinine ratio (300 mg/g) has poor sensitivity and specificity, requiring a full 24-hour urine for accurate results. Higher thresholds have not been adequately studied.