Background Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. Methods The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. Results We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220+ B cells and a robust anti-pig antibody production. In addition, early donor-stimulated IL-17 production, but not IFN-γ production, dominated during early acute rejection. Recipient treatment with donor apoptotic 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide-treated splenocytes (ECDI-SP) significantly inhibited anti-donor IL-17 response, and when combined with B cell depletion and a short course of rapamycin led to survival of pig islet xenografts beyond 100 days in ~65% recipients. Interestingly, treated recipients in this model experienced late rejection between 100 – 200 days posttransplant, which coincided with B cell reconstitution and an ensuing emergence of a robust anti-donor IFN-γ, but not IL-17, response. Conclusions These findings reveal that early and late rejection of pig islet xenografts may be dominated by different immune responses, and that maintenance of long-term xenogeneic tolerance will require strategies that target the temporal sequence of anti-xenogeneic immune responses.

Absence of anti‐HBc reactivity with detectable anti‐HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti‐HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow‐up (range: 2.6–84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti‐HBs as only serological marker. Isolated anti‐HBs OBIs differed from anti‐HBc‐reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti‐HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti‐HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti‐HBs level at index (48% vs 9% with anti‐HBs >100 IU/L) and higher frequency of anti‐HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow‐up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti‐HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti‐HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

BACKGROUND Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow‐up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti‐HCV, anti‐HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini‐pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID‐NAT re‐testing. A follow‐up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non‐reactive and NAT non‐repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow‐up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti‐HBc or anti‐HBs reactivity was observed in 22% of cases. CONCLUSION Follow‐up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false‐positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

The hepatitis B virus (HBV) remains a high priority for Chinese blood banks due to the high prevalence of infection. HBV blood safety has been significantly improved by the implementation of highly sensitive and specific serological and molecular HBV screening assays. The multiplication of viral markers tested and the ever-increasing analytical sensitivity of the tests can make the interpretation of the results difficult. False-positive or indeterminate results may lead to permanent donor deferrals and conflicts between donors and blood banks. To avoid blood shortages, blood services aim to limit unnecessary donor losses by developing procedures for the re-entry of donors temporarily deferred due to an unconfirmed HBV reactivity. The development of such procedures based on donor follow-up and HBV confirmation remains limited. A review of the scarce data available revealed considerable heterogeneity in testing methods and re-entry algorithms, limited validation studies, and a lack of accurate assessment of the residual infectious risk potentially associated with donor re-entry. In conclusion, systematic and widely validated confirmatory testing and prolonged follow-up are essential for safe re-entry of temporary deferred donors. Standardization of HBV testing methods and the establishment of dedicated expert laboratories are needed because of the complexity of HBV infection in blood donors.

Objective: To investigate the utility of intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters in hypothalamus for monitoring the effect of Exendin-4 (Ex-4) intervention on the feeding behavior in obese diabetic rats within early feeding. Methods: 21 obese and 19 non-obese rats which were treated with streptozotocin injections were initially divided into an obese diabetes group (OD, n = 10), a non-obese diabetes group (D, n = 8), an obese group (O, n = 9) and a non-obese group (N, n = 9). Then, the rats in the 4 groups received subcutaneous injections of Ex-4, and feeding behavior was examined at 5, 35, 65, 95, and 125 min. The hypothalamic function was evaluated by IVIM-DWI. Finally, the relationship between the hypothalamic function and the amount of food intake was analyzed. Results: In comparison with the N group, the food intake significantly decreased in the O , OD, and D groups in response to Ex-4. Furthermore, a significant positive correlation was found between food intake and D values at different times from 5 to 125 min after Ex-4 intervention in all 4 groups. Conclusion: A direct correlation between the change of hypothalamic function and feeding behavior was detected in OD rats with Ex-4 intervention in the early feeding period. The hypothalamic D value derived from IVIM-DWI is promising to reflect the dynamic change of hypothalamic function due to intervention.