Allergology International最新文献

Background: Because different immunosuppressive therapies have their own characteristic properties to inhibit/enhance the production of various cytokines in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), cytokine profile dynamics could be used to predict and monitor the therapeutic response across different treatments, when assessed at baseline and following therapy.

Methods: This retrospective analysis was performed to assess how changes in cytokine profiles available in clinics contributed to an optimal therapeutic response in SJS/TEN patients. We included 31 patients with SJS/TEN, treated with standard corticosteroids (n = 9), pulse corticosteroids (n = 11), intravenous immunoglobulins (n = 4), plasmapheresis (n = 6), and supportive therapy (n = 1).

Results: High granulysin (≥ 1.6 ng/ml) and soluble Fas ligand (≥ 2540 pg/ml) levels at baseline were strong predictors for the failure of standard corticosteroid therapy. We found that standard corticosteroid treatment inhibited not only Th1 cytokines but also monocyte-derived cytokines in patients exhibiting an adequate treatment response. Although pulse corticosteroids have a fundamentally similar effect as standard corticosteroids on cytokine profiles, pulse corticosteroids more efficiently reduced monocyte-derived cytokines. Intravenous immunoglobulins suppressed interferon-γ and interleukin (IL)-12p40 production more efficiently compared with standard corticosteroids and other immunosuppressive agents. A profound decrease in granulocyte colony-stimulating factor and IL-10 associated with a marked increase in IL-12 was specifically detected in SJS/TEN patients treated with plasmapheresis.

Conclusions: We can select the most appropriate treatment option for individual patients following the failure of standard corticosteroids by examining treatment-relevant cytokine profiles before and after treatment. We propose a treatment algorithm that can serve as a decision-making tool for tailored therapy selection.

Background: Inducible co-stimulator (ICOS) regulates the proliferation and differentiation of a variety of T cells. It is considered to be a potential immunotherapy target and marker for many diseases. Its dual role is worthy of further study in allergic rhinitis (AR).

Methods: We quantified ICOS-expressing T helper (Th) cells and changes in the proportions of Th1/Th2/Th9/Th17/follicular helper T (Tfh) and regulatory T cells (Treg) in the peripheral blood of patients with AR and in healthy controls (HC). All participants completed the Total Nasal Symptom Scores (TNSS) questionnaire. Ten patients with AR who underwent subcutaneous immunotherapy (SCIT) were followed for 6, 12, 24 and 36 months after treatment. In functional experiments, peripheral blood from ten dust mite-sensitized AR patients was analyzed for key T-cell subsets and ICOS expression under different stimulation conditions.

Results: The patients with AR showed higher levels of Th2, Th9, Th17 and Tfh compared with HCs, while the levels of Th1 and Treg were lower. However, ICOS expression on these T-cell subsets was elevated. TNSS correlated positively with Th2 and ICOS-expressing Th2. TNSS and ICOS-expressing Th2 decreased significantly with the passage of SCIT time. Functional assays showed that ICOS/ICOS ligand (L) stimulation increased the level of Th2, while phosphatidyl inositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) inhibition reduced Th2 levels.

Conclusions: Our findings demonstrate that ICOS expression and effects are linked to the differentiation of T cells in AR, especially Th2 cells, which suggests ICOS-expressing Th2 cells as a potential therapeutic target for AR.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a severe T cell-mediated hypersensitivity reaction. T cells in DReSS are stimulated via the p-i mechanism (pharmacological interaction with immune receptors), where the drug shows an off-target binding to immune receptors (TCR and/or HLA) leading to an unorthodox activation of T cells. P-i stimulations are particularly strong in DReSS, as the causative drugs are typically administered at high doses for prolonged durations (>7 days) and bind with relatively high affinity to a specific HLA allele and/or TCR. This mechanism results in delayed yet profound immune activation, progressing through four distinct phases. The p-i concept provides a unifying explanation for many puzzling aspects of DReSS and has significant implications for diagnosis, management, and prevention. Recognizing drug concentration, therapy duration, and HLA affinity as key determinants of strong p-i-mediated immune activation can improve risk assessment, early diagnosis, and intervention strategies for DReSS.

Background: The conventional in vitro lymphocyte transformation test (LTT) for diagnosing drug hypersensitivity reactions (DHRs) is limited by low sensitivity. To improve detection and assess T cell activation strength, we adapted this test to a cytokine-based assay (Cyto-LTT) by measuring IL-5, IL-13, IFN-γ, granzyme B and granulysin secretion.

Methods: We retrospectively analyzed 851 positive Cyto-LTT results (from a total 6058 Cyto-LTT) from a Swiss drug hypersensitivity diagnostic laboratory's database, including 97 patients with Drug Rash with Eosinophilia and Systemic Symptoms (DReSS) and 754 patients with exanthems, including urticarial, maculo- and maculopapular-rash. Cytokine responses measured across three drug concentrations of amoxicillin (n = 734), aromatic sulfonamides (n = 81), or vancomycin (n = 36) were evaluated for dose-dependency and the correlation to the clinical manifestations. A grading system defined strong responses as cytokine stimulation indices (SI) above the 75th percentile (per cytokine) in the exanthem group which served as a comparator for the DReSS cases.

Results: Cytokine responses increased dose-dependently. DReSS cases exhibited significantly stronger cytokine secretions compared to exanthem cases (p < 0.001), with strong responses observed in 62.9 % of DReSS patients versus 33.6 % of exanthem cases.

Conclusions: Cyto-LTT reveals dose-dependent T cell activation in delayed drug hypersensitivity reactions, challenging the notion that drug allergic reactions are dose-independent. The assay not only identifies the culprit drug but also quantifies immune activation strength. Stronger responses were more frequent in DReSS, suggesting the test may also inform risk assessment-particularly in guiding caution with structurally related compounds or in patients at risk for severe or recurrent reactions.