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

Mendelian Genetics of Human Susceptibility to Fungal Infection

Contains fulltext : 137429.pdf (Publisher’s version ) (Closed access)A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens

Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-gamma stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with AIRE and STAT1 GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14+ monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-gamma stimulation, as well as the levels of STAT1 mRNA. The mean STAT1 protein levels in CD14+ monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-gamma stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-gamma-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased STAT1 mRNA or anti-IFN-gamma autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased AIRE-/- monocyte surface expression of IFN-gamma receptor 2. Our data show that, in contrast to patients with STAT1 GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN-gamma stimulation

Substratos e estacas com e sem folhas no enraizamento de Luehea divaricata Mart. Substrates and stem cuttings with and without leafs on rooting of Luehea divaricata Mart.

O objetivo deste trabalho foi avaliar a influência do substrato e do tipo de estaca no enraizamento de Luehea divaricata. O experimento foi realizado no Viveiro Florestal da Universidade Federal de Santa Maria (UFSM), no período de dezembro de 2006 a fevereiro de 2007. Foram utilizadas estacas herbáceas (com folha e sem folha), de plantas matrizes com aproximadamente dois anos de idade e diferentes tipos de substrato (turfa, Plantmax®, vermiculita, Mecplant®) em arranjo fatorial 2x4. O delineamento experimental foi inteiramente casualizado, com cinco unidades experimentais por repetição e 10 repetições por tratamento. As avaliações foram realizadas 60 dias após a implantação do experimento. As variáveis observadas foram sobrevivência, enraizamento, número de raízes, comprimento das raízes, matéria seca das raízes e matéria seca da parte aérea. O tipo de estaca apresentou influência em todas as variáveis estudadas, tendo em vista que 100% das estacas sem folha morreram antes de enraizar. Estacas cultivadas em Plantmax® apresentaram maior comprimento das raízes quando comparadas ao substrato Mecplant®. A utilização dos substratos turfa e Plantmax® permitiu obter maiores valores de matéria seca da parte aérea e matéria seca das raízes. Estacas com um par de folhas cultivadas em Plantmax® são indicadas na estaquia de Luehea divaricata.<br>An experiment was carried out to evaluate the influence of substrate and type of stem cuttings on the rooting of Luehea divaricata. The experiment was conducted at a Forest Seedbed at the Federal University of Santa Maria (UFSM), from December 2006 to February 2007. Herbaceous stem cuttings were used (with and without leaf), of plant matrices of approximately two years of age distributed as substrate (peat, Plantmax®, vermiculite, Mecplant ®) in factorial 2 x 4. The experimental design was completely randomized and consisted of bifactorial combination with five units per repetition and 10 repetitions per treatment. The evaluations have been performed 60 days after the implantation of the experiment. The variables observed were: survival, rooting, number of roots, length of roots and dry mass of the roots and of the aerial part. The type of stem cuttings presented influence for the variables analyzed, considering that 100% of the stem cuttings without leaf died before rooting. Stem cuttings cultivated in Plantmax® showed higher length of the roots than Mecplant®. The use of peat and Plantmax® substrate enabled more values for the dry mass of leaf and roots. Stem cuttings with a pair of leaf grown in Plantmax ® are indicated in the vegetative propagation of Luehea divaricata

Enraizamento de estacas, crescimento e respostas anatômicas de mudas clonais de cacaueiro ao ácido indol-3-butírico Stem cutting rooting, growth and anatomical responses of cacao tree clonal changes to the indole-3-butyric acid

Avaliaram-se os efeitos do ácido indol-3-butírico (AIB) no crescimento e na morfologia interna de quatro clones de Theobroma cacao (CCN-10, CP-53, PS-1319 e CA-1.4). O AIB foi aplicado na base da estaca de caule, em talco inerte, nas concentrações de 2; 4; 6 e 8 g kg-1, juntamente com o controle (sem AIB). A avaliação do crescimento de raízes, caule e folhas dos quatro clones foi realizada aos 160 dias após o estaqueamento (DAE) para todas as concentrações de AIB, período também em que se realizou a coleta de material para os estudos anatômicos dos diversos órgãos, mas somente para a concentração de 4g kg-1 AIB e o controle. O clone CA-1.4 apresentou incremento na biomassa seca de raiz (BSR) com o aumento das concentrações de AIB, ao passo que, nos demais clones, houve diminuições de BSR a partir dos 4 g kg-1 AIB. O mesmo fato foi observado para a biomassa seca de caule (BSC) e de folha (BSF), exceto para a BSC do CCN-10 que não respondeu ao incremento das concentrações de AIB. Houve aumento de área foliar total para os clones CP-53 e PS-1319 com o incremento de AIB até 4 g kg-1, enquanto o aumento do número de folhas ocorreu somente para os clones CA-1.4 e CP-53 até as concentrações 8 e 4 g kg-1 AIB, respectivamente. Houve diminuição do número de estacas mortas para os clones CA-1.4 e CCN-10 até 8 g kg-1 de AIB e para o CP-53 até 4 g kg-1 de AIB. As melhores concentrações de AIB para o enraizamento de estacas de ramos dos clones de cacaueiros CP-53, PS-1319 e CCN-10 foram de 4, 4 e 6 g kg-1 AIB, respectivamente, enquanto para o clone CA-1.4 foi de 8 g kg-1 AIB; o aumento da concentração de AIB promoveu mudanças anatômicas nos órgãos vegetativos de todos os clones, influenciando na atividade do câmbio vascular e induzindo a formação de um maior número de raízes adventícias nas estacas.<br>The effects of indole-3-butyric acid (IBA) on growth and internal morphology of four clones of Theobroma cacao (CCN-10, CP-53, PS-1319 and CA-1.4) were evaluated. The IBA was applied in the base of stem cuttings, as an inert talc, in mixture concentrations of 2, 4, 6 and 8 g kg-1 together with the control, without IBA. The evaluation of the growth of roots, stem and leaves of the four clones were accomplished by 160 days after the cutting (DAC) for all the IBA concentrations. However, the anatomical studies of the several plant organs were also made to the 160 DAC, but only for the concentration of 4g kg-1 IBA and the control. The clone CA-1.4 presented increment in the root dry biomass (RDB) with the increase of the IBA concentrations, while for the other clones there were decreases of RDB starting from the 4 g kg-1 IBA. The same fact was observed for the stem and leaf dry biomass, except for CCN-10 that did not answer to the increment of the concentrations of IBA. There was an increase of the total leaf area for the clones CP-53 e PS-1319 with the increment of the IBA (concentration up to 4 g kg-1), while the leaves number only increased for the clones CA-1.4 and CP-53, concentrations up to 8 and 4 g kg-1 IBA, respectively. There was a decrease in the number of dead cuttings for the clones CA-1.4 and CCN-10 (up 8 g kg-1) of IBA and for the CP-53 (up to 4 g kg-1 of IBA). The best IBA concentrations for the branch cutting rooting of the cacao clones CP-53, PS-1319 and CCN-10 were of 4, 4 and 6 g kg-1 respectively, while for the clone CA-1.4 was the one of 8 g kg-1; the increase of the IBA concentration promoted anatomical changes in the plant organs of all the clones, influencing the activity of the vascular cambium in the stem and inducing the formation of a larger number of adventitious roots in the stem cuttings