Use of Mixed Lymphocyte Reaction Assay to Evaluate Immune Tolerance before Kidney Transplantation with an Immunosuppression-Free Protocol following Hematopoietic Stem Cell Transplantation from the Same Donor.

Several cases of kidney transplantation after hematopoietic stem cell transplantation (HSCT) from the same donor for end-stage renal disease have been reported. In those cases, immunosuppressive drugs were discontinued since immune tolerance was supposed to be induced. Theoretically, the recipient's immune system recognizes the kidney allograft as its own tissue with the same human leukocyte antigen (HLA) profile, and the kidney allograft will not be rejected, even without the use of immunosuppressive agents. However, almost all recipients receive immunosuppressants in the early stages after kidney transplantation owing to concerns of acute rejection. Here, we report a successful case of post-HSCT kidney transplantation without the use of immunosuppressive drugs, in which a mixed lymphocyte reaction (MLR) assay was used to evaluate immune tolerance before kidney transplantation. The patient was a 25-year-old woman. Five years prior, she developed acute myeloid leukemia and underwent HLA-half-matched peripheral blood stem cell transplantation. Thereafter, she was in remission of the acute myeloid leukemia, but 1 year later, she developed renal graft-versus-host disease. Subsequently, the patient's renal function gradually deteriorated to end-stage renal failure, and she underwent kidney transplantation with the previous stem cell donor: her mother. HLA typing of donor and recipient showed a complete chimerism in the peripheral blood. The pretransplantation complement-dependent cytotoxic crossmatch and flow cytometric T-cell crossmatch results were both negative, and HLA antibody measurements were all negative. The MLR assay revealed no T-lymphocyte reaction to the donor; therefore, immunosuppressants were not used. Two years after transplantation, the patient's serum creatinine concentration was around 0.8 mg/dL (down from 4 mg/dL before transplantation). No abnormalities were observed in a renal biopsy performed after 3 months. Our study, along with others, indicates that immune tolerance to a donor develops in post-HSCT kidney transplantation from the same donor.

Endoscopic balloon dilations for strictures of rectum, ileocecal valve and duodenum in a patient with X-linked inhibitor of apoptosis deficiency: a case report

X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency and gastrointestinal (GI) lesions in XIAP deficiency are similar to Crohn’s disease. For patients with Crohn’s disease, endoscopic balloon dilation (EBD) is known to be a standard procedure for intestinal strictures including upper GI tract. However, there are no articles which mention the efficacy of EBDs for the strictures in upper GI tract in patients with XIAP deficiency. Herein, we describe an 18-year-old male with XIAP deficiency in whom EBDs for the rectum, ileocecal valve (ICV), and duodenum were performed. Before hematopoietic stem cell transplantation (HSCT), GI endoscopy revealed strictures of the rectum, ICV and duodenum with active ulcers. Although these ulcers healed after HSCT, the strictures progressed. Therefore, we performed EBDs for the strictures of the rectum, ICV, and duodenum. In contrast studies, we did not find any other strictures in the small intestine. Throughout the patient’s clinical course, no complications of EBD occurred. He started eating after EBDs, but abdominal symptoms did not relapse without any dietary restrictions. Our case suggests that EBD could be an effective and safe procedure for intestinal strictures including upper GI tract after HSCT in patients with XIAP deficiency.

Performance of qualitative and quantitative antigen tests for SARS-CoV-2 in early symptomatic patients using saliva

BackgroundThe rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent need for the prevention and containment of disease outbreaks in communities. Although the gold standard is polymerase chain reaction (PCR), antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) that can yield results within 30 minutes. MethodsWe evaluated performance of ICA and CLEIA using 34 frozen PCR-positive specimens (17 saliva and 17 nasopharyngeal swab) and 307 PCR-negative samples. ResultsICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 (83%) of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with positivity of 82% in saliva and 100% in NPS. CLEIA was negative in 3 samples with low viral load by PCR. ConclusionsThese results suggest that use of ICA should be limited to earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.

Mass screening of asymptomatic persons for SARS-CoV-2 using saliva

BackgroundCOVID-19 has rapidly evolved to become a global pandemic due largely to the transmission of its causative virus through asymptomatic carriers. Detection of SARS-CoV-2 in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of PCR testing. Additionally, although self-collected saliva has significant logistical advantages in mass screening, its utility as an alternative specimen in asymptomatic persons is yet to be determined. MethodsWe conducted a mass-screening study to compare the utility of nucleic acid amplification, such as reverse transcriptase polymerase chain reaction (RT-PCR) testing, using NPS and saliva samples from each individual in two cohorts of asymptomatic persons: the contact tracing cohort and the airport quarantine cohort. ResultsIn this mass-screening study including 1,924 individuals, the sensitivity of nucleic acid amplification testing with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%) and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%. The true concordance probability between the nasopharyngeal and saliva tests was estimated at 0.998 (90%CI:0.996-0.999) on the estimated airport prevalence, 0.3%. In positive individuals, viral load was highly correlated between NPS and saliva. ConclusionBoth nasopharyngeal and saliva specimens had high sensitivity and specificity. Self-collected saliva is a valuable specimen to detect SARS-CoV-2 in mass screening of asymptomatic persons.

Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification

Rapid detection of SARS-CoV-2 is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel "2019 Novel Coronavirus Detection Kit (nCoV-DK)" halves detection time by eliminating the steps of RNA extraction and purification. We evaluated concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 fresh samples by the direct method and 55/71 corresponding frozen samples by the nCoV-DK. The overall concordance rate of the virus detection between the two methods was 94.4% (95% CI, 86.2-98.4). Concordance rates were 95.2% (95% CI, 83.8-99.4), 95.5% (95% CI, 77.2-99.9), 85.7% (95% CI, 42.1-99.6) in nasopharyngeal swab, saliva, and sputum samples, respectively. These results indicate that the nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error.

Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva

We prospectively compared the efficacy of PCR detection of SARS-CoV-2 between paired nasopharyngeal and saliva samples in nine COVID-19 patients. SARS-CoV-2 was detected in saliva in 8 of 9 (89%) patients and in all 11 samples taken within 2 weeks after disease onset. Viral load was equivalent at earlier time points but declined in saliva than nasopharyngeal samples. PCR negativity was also concordant in all 27 saliva samples from 24 patients between nasopharyngeal and saliva samples. These results suggest that saliva is a reliable noninvasive alternative to nasopharyngeal swabs and facilitate widespread PCR testing in the face of shortages of swabs and protective equipment without posing a risk to healthcare workers.