{"id":385130,"date":"2024-10-23T00:01:00","date_gmt":"2024-10-22T22:01:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=385130"},"modified":"2024-09-02T10:30:02","modified_gmt":"2024-09-02T08:30:02","slug":"s-aureus-infection-in-pediatric-ad","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/s-aureus-infection-in-pediatric-ad\/","title":{"rendered":"S. aureus infection in pediatric AD"},"content":{"rendered":"\n

The skin microbiome of patients with atopic dermatitis (AD) exhibits reduced bacterial diversity.\nThe pathogen Staphylococcus aureus (S. aureus)<\/em> often predominates.\nThis gram-positive bacterium intensifies inflammatory processes and is associated with acute AD episodes.\nA study published in 2024 in JCI Insight<\/em> by Clowry et al.\nprovides insights into the systemic and cutaneous immune signatures associated with S. aureus-infected<\/em>pediatric AD. <\/strong><\/p>\n\n\n\n

For the study by Clowry et al.\n93 AD patients aged 0-16 years were recruited [6].\nOf these, 12 had a confirmed S. aureus skin infection<\/em>based on clinical criteria (“ADS.aureus”) [7].\nThe clinical criteria included oozing, pustule formation, abscesses and\/or crust formation as well as positive bacterial smear results.\nThe remaining 46 AD patients did not meet the clinical criteria for the diagnosis of S. aureus skin infection<\/em>(AD control group).\nThe skin-healthy control group consisted of 35 participants who had neither an active S. aureus skin infection<\/em>nor a history of atopy. <\/p>\n\n

S. aureus skin infection<\/em>was associated with higher AD severity<\/h3>\n\n

Systemic immunological profiles were created for all 93 patients and, in addition, local skin immune profiles were created for a subgroup (n=69) [6].\nThis subgroup included 9 “ADS.aureus” patients, 32 patients from the AD control group and 28 skin-healthy controls.\n“AD.aureus” patients had a higher AD severity compared to the AD control group (mean EASI scores of 29.4-32 compared to 14.8-15).\nIn addition, a greater number of patients in the “ADS.aureus” group were affected by high levels of S. aureus colonization<\/em>in both lesional (67% and 37%, respectively) and non-lesional (30% and 5%, respectively) skin.\nAll patients in the “ADS.aureus” group had moderate or high levels of S. aureus<\/em> on the lesional skin, 60% had colonization of the non-lesional skin and 66% had nasal colonization.\nIn contrast, the AD control group showed no clinical signs of S. aureus infection<\/em>.\nIn 51% of these patients, S. aureus<\/em> was identified on the lesional AD skin, in 30% on the non-lesional AD skin and 48% had nasal colonization.\n“AD.aureus” patients were less likely to be taking immunomodulatory systemic drugs (8-11% compared to 41-46% in the AD control group). <\/p>\n\n

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Microbiome research adds an important level to the knowledge of pathogenetic processes in AD.\nIt is now known that the cutaneous microbiota can influence and modulate immune responses in the skin, with S. aureus<\/em> appearing to play a key role [1].\nWhile S. aureus<\/em> is only detectable on healthy skin in <5% of all swabs, it is found in children with AD in >90% of cases [2].\nThe already weakened barrier function of the skin in AD can be further impaired by S. aureus <\/em>, as the bacterium has proteases that further reduce the integrity of the barrier [3].\nThis is because the protease activity enables penetration into the epidermis, which results in stimulation of Th2 cytokines, so that S. aureus<\/em> can be found not only in the epidermis but also in the dermis of AD lesions [4].\nFurthermore, S. aureus<\/em> expresses an \u03b1-toxin – a pore-forming protein that damages the cell membrane of keratinocytes [5]. <\/td><\/tr><\/tbody><\/table><\/figure>\n\n

Immunological profiles of “ADS.aureus” vs. AD control group?<\/h3>\n\n

The initial analysis focused on the totality of “AD.aureus” antigen-specific memory T cell responses [6].\nSkin-selective homing of memory and effector T cells is an important immunologic process in the pathophysiology of AD.\nCutaneous lymphocyte-associated antigen (CLA) is a skin homing receptor that defines a subset of circulating memory T cells To better understand the skin-directed “AD.aureus” antigen-specific memory T cell responses, the staining panel was expanded to include CLA [8]. <\/p>\n\n

Characterization of circulating T-cells and S. aureus antigen-specific<\/em>T-cell responses associated with S. aureus-infected<\/em>relapses: <\/strong>To determine whether different circulating T-cell phenotypes and S. aureus antigen-specific<\/em>T cell responses can be identified between “ADS.aureus”, the AD control group and the skin-healthy controls, peripheral blood mononuclear cells (PBMCs) were collected from all 93 recruited patients [6].\nCirculating leukocyte populations were analyzed to determine the proportion of specific T-cell subsets by flow cytometric staining.\nTo assess S. aureus antigen-specific<\/em>systemic responses, total PMBCs were labeled with carboxyfluorescein succinimidyl ester (CFSE) and cultured in vitro in the presence of heat-inactivated S. aureus<\/em> (strain AD08).\nCells stimulated with the medium alone or with staphylococcal enterotoxin A (SEA) represented negative and positive controls, respectively.\nOn day 8, cells were collected and stained with a series of fluorochrome-conjugated antibodies against surface and intracellular markers (Table 1).<\/strong> Fluorescence-activated cell sorting (FACS) was used to identify the specified T cell subsets. <\/p>\n

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The proportions of circulating systemic T-cell subsets and S. aureus antigen-specific<\/em>memory T-cell subsets identified in the three groups were entered into a Bayesian multinomial model. <\/p>\n\n