What is in a name? Agreed nomenclature for kidney function and disease from a KDIGO consensus conference–optional now but probably mandatory in a year or two, so the article is worth a read now. The issue also contains some great reviews–T memory and B cells, HCC management and the tricky issues of transplantation in Amyloid, and APT deficiency are illuminated in these pages. Innate solutions for islets and the interplay between the heart and kidney, among many other subjects, will keep you interested in a great issue of the journal.

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

Evidence for GTKO/β4GalNT2KO Pigs as the Preferred Organ-source for Old World Nonhuman Primates as a Preclinical Model of Xenotransplantation

Cui Y, Yamamoto T, Raza SS, et al.
Transplantation Direct: August 2020 - Volume 6 - Issue 8 - p e590

The quest for successful pig to human transplantation continues to delve into the depths of the immune response to pig carbohydrates. That quest has delivered Triple-knockout (TKO) pigs which have the 3 known pig carbohydrate xenoantigens deleted.  The question asked in this paper: is this enough is answered in the negative using 72 baboon sera. It is very hard to find a non-human primate that does not have natural antibodies directed to a fourth xenoantigen exposed in the cells of TKO pigs.  The researchers tested anti-pig IgM/IgG binding, and complement-dependent cytotoxicity by flow cytometry to α1,3-galactosyltransfearse gene-knockout (GTKO) and GTKO/β4GalNT2KO cells which they concluded would be a better choice for organ xenotransplantation studies.

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Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Qian Zhang et al.
Science. 24 Sep 2020: eabd4570. DOI: 10.1126/science.abd4570

This Article documented an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, this study experimentally defined LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. Human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Auto-antibodies against type I IFNs in patients with life-threatening COVID-19

Paul Bastard et al.
Science. 24 Sep 2020: eabd4585. DOI: 10.1126/science.abd4585

This article reports that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity

Carolyn Rydyznski Moderbacher et al.
Cell (September 2020), doi: https://doi.org/10.1016/j.cell.2020.09.038.

This study measured SARS-CoV2-specific antibodies (including neutralizing antibodies), SARS-CoV-2-specific CD4+ T cells, and SARS-CoV-2-specific CD8+ T cells in all individuals in 54 patients. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals > 65 years old. Scarcity of naive T cells was also associated with ageing and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between ageing and impaired adaptive immune responses to SARS-CoV-2.

Tocilizumab for severe COVID‐19 in solid organ transplant recipients: a matched case‐control study

Marcus R. Pereira et al.
American Journal of Transplantation. 18 September 2020. https://doi.org/10.1111/ajt.16314

This study evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID‐19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID‐19, 29 (24.8%) received tocilizumab. 90‐day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, p=0.03). When compared to control patients matched by age, hypertension, chronic kidney disease and administration of high dose corticosteroids, there was no significant difference in mortality (41% v. 28%, p=0.27), hospital discharge (52% v. 72%, p=0.26) or secondary infections (34% v. 24%, p=0.55). Among patients who received tocilizumab, there was also no difference in mortality based on level of oxygen support (intubated v. not intubated) at time of tocilizumab initiation. In this matched control cohort study, tocilizumab appeared to be safe but was not associated with decreased 90‐day mortality.

Sept. 26 - Researchers analysed almost half a million individual cells to build an extensive draft cell atlas of the human heart.They say it shows a huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells, and the intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

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Sept. 24 - Researchers at EPFL have developed an approach to print tiny tissues that look and function almost like their full-sized counterpart. Measuring just a few centimeters across, the mini-tissues could allow scientists to study biological processes—and even test new treatment approaches—in ways that were previously not possible.

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Sept. 22 - Colleagues at University Hospital Erlangen, Erlangen, Germany, conducted a study to assess a new diagnostic approach to human leukocyte antigen (HLA) typing in kidney transplant recipients. The approach utilizes cultured renal tubular cells from urine samples to facilitate clinical assessment of donor specificity of de novo occurring HLA antibodies.

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Sept. 26 - A team led by Chinese researchers say they have succeeded in producing genetically modified pigs with cells that are more compatible with the human immune system, paving the way for safe and effective organ transplants from animals to humans.

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

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