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Background: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice., Objective: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities., Methods: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7., Results: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%)., Conclusions: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies have linked daily pollen counts to respiratory allergic health outcomes, but few have considered allergen levels., Objective: We sought to assess associations of grass pollen counts and grass allergen levels (Phl p 5) with respiratory allergic health symptoms in a panel of 93 adults with moderate-severe allergic rhinitis and daily asthma hospital admissions in London, United Kingdom., Methods: Daily symptom and medication scores were collected from adult participants in an allergy clinical trial. Daily counts of asthma hospital admissions in the London general population were obtained from Hospital Episode Statistics data. Daily grass pollen counts were measured using a volumetric air sampler, and novel Phl p 5 levels were measured using a ChemVol High Volume Cascade Impactor and ELISA analyses (May through August). Associations between the 2 pollen variables and daily health scores (dichotomized based on within-person 75th percentiles) were assessed using generalized estimating equation logistic models and with asthma hospital admissions using Poisson regression models., Results: Daily pollen counts and Phl p 5 levels were each positively associated with reporting a high combined symptom and medication health score in separate models. However, in mutually adjusted models including terms for both pollen counts and Phl p 5 levels, associations remained for Phl p 5 levels (odds ratio [95% CI]: 1.18 [1.12, 1.24]), but were heavily attenuated for pollen counts (odds ratio [95% CI]: 1.00 [0.93, 1.07]). Similar trends were not observed for asthma hospital admissions in London., Conclusions: Grass allergen (Phl p 5) levels are more consistently associated with allergic respiratory symptoms than grass pollen counts., Competing Interests: Disclosure statement The PollenLITE trial was awarded by the Efficacy and Mechanism Evaluation Programme, is funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership, and is jointly sponsored by King’s College London and Guy’s and St Thomas’ NHS Foundation Trust. Additional funding was provided by the King’s Health Partners Research and Development Challenge Fund. This work was also supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The work of the UK Small Area Health Statistics Unit is overseen by the UK Health Security Agency and partly funded by the MRC Centre for Environment and Health (grant no. MR/L01341X/1), the NIHR through its Health Protection Units at Imperial College London in Environmental Exposures and Health and in Chemical and Radiation Threats and Hazards, Health Data Research UK, and infrastructure support to the Department of Epidemiology and Biostatistics provided by the NIHR Imperial Biomedical Research Centre. This paper does not necessarily reflect the views of the UK Health Security Agency, the NIHR, or the Department of Health and Social Care. E.F. is supported by the Imperial College Research Fellowship. J.T.M.B. was supported by a Higher Education Funding Council for England Clinical Senior Lectureship Award during the period the PollenLITE study was conducted. The funding sources had no role in the study design, collection, analysis and interpretation of data, writing of the report, and decision to submit the paper for publication. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The immunologic defect in X-linked immunodeficiency and hyperimmunoglobulinemia M (HIM) are related to defective expression of the CD40 ligand (CD40L). We have studied two female patients with HIM to evaluate the role of CD40/CD40L in the pathogenesis of impaired immunoglobulin switching. In addition to recurrent infections characteristic of humoral immunodeficiencies, the two patients had chronic hepatitis caused by type C virus. Phenotypic characterization of peripheral blood mononuclear cells showed a similar picture in both patients, with a reduction in the absolute numbers of CD4 cells and increased numbers of CD8 and CD3/DR cells. B cells (CD19+) were reduced in one patient, but CD40 was expressed on all CD19+ cells in both patients. The expression of CD40L was normal on peripheral blood mononuclear cells from the two patients with HIM on both resting and stimulated cells. The combination of anti-CD40 and cytokines (interleukin-2, interleukin-4, and interleukin-10) was able to restore proliferative capacity to anti-IgM. Peripheral blood mononuclear cells from the two patients with HIM showed a high spontaneous production of IgM in vitro and no production of IgG or IgE. Our data suggest that the defect of isotype switching in female patients with HIM is not related to defective expression of the CD40/CD40L receptor system. A possible role for chronic hepatitis C virus infection in the pathogenesis of the disease is suggested by the detection of specific production of anti-hepatitis C virus IgM.

In this study we describe a series of nine patients affected by acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who had hypereosinophilia and hyperimmunoglobulinemia E (hyper-IgE) with chronic dermatitis and recurrent staphylococcal infections. These patients had features similar to those present in hyper-IgE syndrome, a primary immunodeficiency disease. In addition, immunologic characterization of these patients with human immunodeficiency virus (HIV) infection, compared with 51 HIV-positive patients without hyper-IgE, both atopic and nonatopic, and three patients affected by the primary hyper-IgE syndrome, also revealed an increase in IgA and a severe decrease in B and CD4+ lymphocytes. Spontaneous in vitro synthesis of IgE by peripheral blood mononuclear cells was confirmed in both hyper-IgE conditions, together with increased levels of circulating eosinophil cationic protein. Serum-soluble CD23, usually increased in atopic conditions and hyper-IgE, was similar to that of normal control subjects in the HIV-positive patients with hyper-IgE. On the basis of our findings, we conclude that a hyper-IgE-like syndrome represents a distinct aspect of the clinical manifestations associated with HIV infection and that the immunologic mechanisms in this condition seem to differ from those known in primary hyper-IgE syndrome, because CD4+ TH2 type cells, which are currently believed to have a role in IgE production, are severely depleted in HIV-positive patients.