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

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against 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 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Agrobacterium tumefaciens を用いたサッマイモの形質転換

Leaf explants from in vitro plantlets of sweetpotato Ipomoea batatas (L.) cv. Regal were used to obtain transgenic plants. Explants were inoculated with a strain LBA 4404 of Agrobacterium tumefaciens which contains a binary vector pBI121 harboring neomicyn phosphotransferase (NPT-II) and β-glucuronidase (GUS) genes. Two procedures were used for obtaining regenerated transgenic plants ; 1) whole explants or 2 ) roots originated from the leaf explants. Regenerated shoots obtained in a selective medium containing 100 mg/ 1 kanamycin, were assayed for kanamycin resistance, GUS histochemical assay and Southern blot analysis. GUS histochemical assays on roots revealed GUS expression in all plants regenerated and rooted on a selection medium containing 100 mg/1 kanamycin.　（和文）　組織培養由来の葉片外植体を用いて、サツマイモ品種Regalの形質転換を行った。使用したベクターはNPT-II遺伝子およびβ-glucuronidase(GUS)遺伝子を組み込んだバイナリーベクターのpBI121であった。これをのAgrobacterium tumefaciensのLBA4404に取り込み、形質転換を 1) 葉片外植体および 2 )葉片外植体起原の根の2種の材料/方法で試した。再分化した植物体については、100ppmカナマイシンを含む培地で選抜を行った。ついで、GUSによる選抜およびGUS遺伝子をプローブとしたサザン検定を行った。カナマイシン培地での選抜およびGUSによる評価を総合すると、組み換え体サツマイモ植物が育成されたことが確認された。継続後誌:近畿大学先端技術総合研究所紀要 = Memoirs of Institute of Advanced Technology, Kinki Universit

Are We on the Right Track: Can Our Understanding of Abscission in Model Systems Promote or Derail Making Improvements in Less Studied Crops?

As the world population grows and resources and climate conditions change, crop improvement continues to be one of the most important challenges for agriculturalists. The yield and quality of many crops is affected by abscission or shattering, and environmental stresses often hasten or alter the abscission process. Understanding this process can not only lead to genetic improvement, but also changes in cultural practices and management that will contribute to higher yields, improved quality and greater sustainability. As plant scientists, we have learned significant amounts about this process through the study of model plants such as Arabidopsis, tomato, rice and maize. While these model systems have provided significant valuable information, we are sometimes challenged to use this knowledge effectively as variables including the economic value of the crop, the uniformity of the crop, ploidy levels, flowering and crossing mechanisms, ethylene responses, cultural requirements, responses to changes in environment, and cellular and tissue specific morphological differences can significantly influence outcomes. The value of genomic resources for lesser-studied crops such as cranberries and grapes and the orphan crop fonio will also be considered