Journal of Allergy and Clinical Immunology最新文献

Background: Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases.

Objective: We sought to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk.

Methods: We undertook a double-blind randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2 g daily of galacto-oligosaccharides and fructo-oligosaccharides in the ratio 9:1) or placebo (8.7 g daily of maltodextrin) powder from less than 21 weeks' gestation until 6 months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was medically diagnosed infant eczema by age 1 year, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by age 1 year.

Results: A total of 652 women were randomized between June 2016 and November 2021 (329 in the prebiotics group and 323 in the placebo group). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by age 1 year (prebiotics 31.5% [103 of 327 infants] vs placebo 32.6% [105 of 322 infants]; adjusted relative risk, 0.98; 95% CI, 0.77-1.23; P = .84). Secondary outcomes and safety measures also did not significantly differ between groups.

Conclusions: We found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of medically diagnosed infant eczema by age 1 year in infants who are at hereditary risk of allergic disease.

Background: Severe hepatitis cases in children are increasingly recognized, but the exact etiology remains unknown in a significant proportion of patients. Cases of indeterminate severe hepatitis (iSH) may progress to indeterminate pediatric acute liver failure (iPALF), so understanding its immunobiology is critical to preventing disease progression. Hemophagocytic lymphohistiocytosis (HLH) is a systemic hyperinflammatory disorder associated with T-cell and macrophage activation with liver injury.

Objectives: We hypothesized that a high proportion of patients with iSH demonstrate systemic T-cell activation similar to HLH before developing iPALF and that the degree of T-cell activation in iSH might correlate with outcomes.

Methods: From 2019 to 2022, 14 patients with iSH and 7 patients with PALF of known, nonimmune etiology were prospectively enrolled. We compared immune signatures of iSH, HLH, known PALF, and healthy controls.

Results: We found that patients with iSH have increased CD8⁺ T-cell activation and high IFN-γ activity similar to HLH. The amplitude of CD8⁺ T-cell activation was predictive of iSH progression to iPALF. We also found that in patients with iSH, ferritin had only modest elevation. However, the ratio of age-normalized plasma soluble IL-2 receptor to ferritin level can distinguish iSH from known PALF and HLH. As proof of concept, we report that in 3 patients with steroid-refractory iSH, emapalumab, an IFN-γ blocking antibody used in combination with steroids, improved liver function and may have prevented progression to PALF.

Conclusions: Flow-based T-cell activation markers could help in early identification and risk stratification for targeted intervention in patients with iSH.

Background: DOCK8 deficiency is a primary immunodeficiency in which allogeneic hematopoietic cell transplantation (HCT) represents the only known cure. We tested the ability of a busulfan-based regimen to achieve reliable engraftment and high levels of donor chimerism with acceptable toxicity in a prospective clinical trial in DOCK8 deficiency.

Objectives: To both evaluate the ability of HCT to reverse the clinical phenotype and to correct the immunologic abnormalities by 1 year post HCT.

Methods: We conducted a prospective HCT trial for recipients with DOCK8 deficiency. Subjects were recruited from October 5, 2010, to December 30, 2022. Donor sources included fully matched related and unrelated donors and haploidentical donors. The reduced toxicity, myeloablative conditioning regimen contained no serotherapy. Graft-versus-host disease (GVHD) prophylaxis included either a calcineurin inhibitor with methotrexate or post-HCT cyclophosphamide (PT/Cy) followed by tacrolimus and mycophenolate mofetil. The trial was later amended to study PT/Cy in all patients. (Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 [NCT01176006].) RESULTS: Thirty-six subjects, both children and adults (median age 16.4 years), underwent HCT for DOCK8 deficiency. Most patients, 33 of 36 (92%), achieved full (≥98%) donor chimerism in whole blood as early as day +30. With a median potential follow-up of 7.4 years, 29 (80.6%) were alive with no evidence of new DOCK8 deficiency-related complications. PT/Cy was effective in reducing the risk of acute GVHD in patients who had received matched unrelated donor and haploidentical transplants, but it was associated with transient delays in immune-reconstitution and hemorrhagic cystitis.

Conclusions: A busulfan-based HCT regimen using PT/Cy for GVHD prophylaxis and a broad range of donor types and hematopoietic cell sources were well tolerated, leading to the reversal of the clinical immunophenotype.

Food allergy is a growing problem that can have a significant impact on both the individual, the family, and society. We are entering a new era of food allergy management with the recent US Food and Drug Administration approvals of 2 therapies for food allergy. IgE is now known to play a critical role in allergic diseases, including food allergy. Ant-IgE therapy has been under investigation for decades and is now approved for asthma, urticaria, nasal polyps, and most recently, IgE-mediated food allergy. Here, we evaluate what is known about the safety and efficacy of anti-IgE therapy as monotherapy and in combination with oral immunotherapy. In addition, we will highlight important practical considerations and key knowledge gaps.

IgE and mast cells play key roles in the pathophysiology of allergic diseases. In 2003, omalizumab was the first anti-IgE mAb licensed in the United States when initially US Food and Drug Administration-approved for the treatment of allergic asthma. Since that time, the number of US Food and Drug Administration-approved indications for treatment with omalizumab has grown to include chronic spontaneous urticaria, chronic rhinosinusitis with nasal polyps, and food allergy. Although omalizumab is generally considered relatively safe and well tolerated, a number of safety concerns have been raised since its initial approval. These concerns focus on specific adverse events of interest, including anaphylaxis, pregnancy, malignancy, cardiovascular events, and infections. For each of these issues, data from clinical trials and postmarketing surveillance have been evaluated extensively. In this review, we examine these safety data, provide context for safety and risk assessments, and summarize a safety profile for each of the adverse events of interest. In doing so, we aim to provide a resource for shared decision making when treatment with omalizumab is being considered.

Self-reported food allergies (FAs) affect approximately 8% of the US pediatric and approximately 10% of the adult population, which reflects potentially disproportionate increases among ethnically and racially minoritized groups. Multiple gaps and unmet needs exist regarding FA disparities. There is reported evidence of disparities in FA outcomes, and the FA burden may also be disproportionate in low-income families. Low family income has been associated with higher emergency care spending and insecure access to allergen-free food. Pharmacoinequity arises in part as a result of structural racism still experienced by historically marginalized populations today. Historically redlined communities continue to experience greater rates of neighborhood-level air pollution and indoor allergen exposure, lack of transportation to medical appointments, poverty, and lower prescription rates of necessary medications. Clinical research needs racially and ethnically diverse participation to ensure generalizability of research findings and equitable access to medical advances, but race reporting in clinical trials has been historically poor. Addressing health disparities in FA is a priority of clinical care, with professional organizations such as the American Academy of Allergy, Asthma & Immunology having a prominent role to play in mitigating the challenges faced by these individuals. In this position statement we recommend some key steps to address this important issue.