Dr. Jeremy R. Chapman, Editor-in-Chief, Transplantation

Natural Killer Cells: Critical Effectors During Antibody-Mediated Rejection of Solid Organ Allografts

Miyairi S, Baldwin WM, Valujskikh A, et al.
Transplantation: May 5, 2020 - Volume Online First

Antibody mediated rejection (AMR) remains a conundrum for all of the organ transplant programs – while we might believe we understand T Cell mediated rejection, only the optimist has the same settled view of AMR. In this great review, these authors dissect the role of Natural Killer Cells as part of the interaction of donor specific antibodies with the innate immune system as critical to AMR in both experimental models and clinical practice. The lead that this data provides to new targets for immune suppression should give us a chance to further improved results.

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COVID-19 infection in kidney transplant recipients at the epicenter of pandemics

Yorg Azzi et al.
Kidney International. (October 2020), doi: https://doi.org/10.1016/j.kint.2020.10.004.

This article investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. 23% of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms, 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.

Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe

Kitty Jager et al.
Kidney International. (October 2020) PMID: 32979369. DOI: 10.1016/j.kint.2020.09.006

This article investigated 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. Data on all patients with a diagnosis of COVID-19 were collected from seven European countries encompassing 4298 patients. COVID-19 attributable mortality was calculated using propensity-score matched historic controls and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis, and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. The authors identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants older than 75 years of age 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy; a highly vulnerable population due to underlying chronic kidney disease and high prevalence of multimorbidity.

COVID‐19 Outcomes in Patients Waitlisted for Kidney Transplantation and Kidney Transplant Recipients

Rebecca Craig‐Schapiro et al.
American Journal of Transplantation.12 October 2020 https://doi.org/10.1111/ajt.16351

This article studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID‐19 between March 13‐ May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, p=0.03) and were at a higher risk of mortality (34% vs. 16%, p=0.02). Intubation was required in one‐third of hospitalized patients in each group, nd portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID‐19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk.

Oct. 14 - NIH will fund a project exploring the ability of artificial intelligence to determine the likelihood of patients accepting or rejecting heart transplants.

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Oct. 16 - The microbiota of infants born by caesarean section resembles that of maternal oral cavity and skin, whereas that of vaginally born infants resembles that of the maternal gut microbiome. A new proof-of-concept study shows that the gut microbiota of C-section-born infants can be restored after delivery via orally administered maternal fecal microbiota transplantation.

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Oct. 14 - Both pancreas transplantation alone (PTA) and islet cell transplantation (ICT) have been associated with peri-operative declines in estimated glomerular filtration rate (eGFR), a decline that is less than that associated with medically managed diabetes. According to Rashikh Choudhury, MD, and colleagues in the department of surgery-division of transplantation surgery at the University of Colorado Hospital, Aurora, PTA and ICT have demonstrated long-term stabilization of chronic kidney disease (CKD) in patients with type 2 diabetes.

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Oct. 13 - A phase 3 trial of omidubicel has shown the graft modality superior to standard umbilical cord blood for bone marrow transplantation in patients with hematologic malignancies, according to topline data released by the agent’s manufacturer.

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The International Pancreas & Islet Transplant Association (IPITA) Conference Organizing Committee is committed to bringing the community together virtually.

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TTS members are invited to attend the FOCIS 2020 Virtual Annual Meeting – THE meeting in translational immunology!

The Federation of Clinical Immunology Societies exists to improve human health through immunology.

The FOCIS 2020 Virtual Annual Meeting on October 28-31, 2020, brings together an interdisciplinary group of world-renowned physicians and researchers to share the latest findings on diseases impacting the immune system.

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