Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms’ anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions—tumor, inflammation and allergy—seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract Andosan^TM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the Andosan^TM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based Andosan^TM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Background: Patients can form antibodies to foreign human leukocyte antigen (HLA) Class I antigens after exposure to allogeneic cells. These anti‐HLA class I antibodies can bind transfused platelets (PLTs) and mediate their destruction, thus leading to PLT refractoriness. Patients with PLT refractoriness need HLA‐matched PLTs, which require expensive HLA typing of donors, antibody analyses of patient sera and/or crossmatching. An alternative approach is to reduce PLT HLA Class I expression using a brief incubation in citric acid on ice at low pH.Methods and Materials: Apheresis PLT concentrates were depleted of HLA Class I complexes by 5 minutes incubation in ice‐cold citric acid, at pH 3.0. Surface expression of HLA Class I complexes, CD62P, CD63, phosphatidylserine, and complement factor C3c was analyzed by flow cytometry. PLT functionality was tested by thromboelastography (TEG).Results: Acid treatment reduced the expression of HLA Class I complexes by 71% and potential for C3c binding by 11.5‐fold compared to untreated PLTs. Acid‐treated PLTs were significantly more activated than untreated PLTs, but irrespective of this increase in steady‐state activation, CD62P and CD63 were strongly upregulated on both acid‐treated and untreated PLTs after stimulation with thrombin receptor agonist peptide. Acid treatment did not induce apoptosis over time. X‐ray irradiation did not significantly influence the expression of HLA Class I complexes, CD62P, CD63, and TEG variables on acid treated PLTs.Conclusion: The relatively simple acid stripping method can be used with irradiated apheresis PLTs and may prevent transfusion‐associated HLA sensitization and overcome PLT refractoriness.

ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.

Background: Refractory patients need to be provided with HLA-matched platelets (PLTs), which require time-consuming cross-matching. Treatment of PLTs with citric acid leads to denaturation of the HLA Class I complexes without significant damage to the PLTs. HLA Class I depleted PLTs could alternatively be used to HLA-matched PLTs for transfusion. These PLTs have verified normal function up to 4-6 h after acid treatment.Materials and Methods: Buffy coat (BC) PLT concentrates were depleted of HLA Class I complexes by incubation in citric acid. The days after acid-treatment, surface expression of HLA Class I complexes, CD62P and CD63 were determined by flow cytometry, in addition to viability and mitochondrial membrane potential (MMP). Thromboelastography (TEG) tested PLT functionality.Results: Expression of HLA Class I complexes was reduced by 70%-75% in acid-treated PLTs compared to untreated PLTs from day 1 through day 7. Controls and acid-treated PLTs showed insignificant loss of MMP stored for 4 days. Analysis of the residual PLT activation and viability showed no significant differences for 4 days of storage. However, the residual PLT activation potential and viability were significantly decreased in acid-treated PLTs and control PLTs after 7 days of storage. Acid treatment caused a significant decrease in the TEG variable, reaction time (R time), for acid-treated PLTs as compared to control PLTs from days 1 through day 3.Conclusion: Our data suggest that extended storage of acid-treated PLTs is possible and will improve flexibility when planning for transfusion of patients with alloimmune PLT refractoriness caused by anti-HLA-antibodies.