PURPOSE: This study aimed to systemically review literature relating to factors that could potentially predict a favorable response to cyclosporine A (CsA) treatment for chronic spontaneous urticaria (CSU). METHODS: A systematic literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. RESULTS: A total of 13 studies (404 patients with CSU and 200 healthy patients) were included. There were only 1 randomized controlled trial (RCT) and 12 non-RCTs. Our systematic review showed that positive autologous serum skin test results, positive baseline basophil histamine release assays, positive baseline basophil activation test responses, elevated baseline plasma D-dimer levels, elevated baseline serum interleukin (IL)-2, IL-5, and tumor necrosis factor-alpha (TNF-α) levels, and low baseline serum IgE levels might assist in predicting favorable CsA responses in CSU patients. Decreased plasma D-dimer levels; and decreased serum IL-2, IL-5, and TNF-α levels were reported to be correlated with clinical improvement after CsA treatment. CONCLUSIONS: Since most positive results were from non-RCT articles and some data were still inconsistent, this systematic review identified no reliable practical biomarker for predicting CsA treatment response in patients with CSU. There were no positive predictors with good consistency and mechanical plausibility.
Basophils ; Cyclosporine ; Histamine Release ; Humans ; Immunoglobulin E ; Interleukin-2 ; Interleukin-5 ; Interleukins ; Plasma ; Skin Tests ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; Urticaria

We previously described a rare case of anaphylaxis presumably induced by carminic acid in cochineal dye used as a food additive. In this study, highly pure carminic acid was added to an albumin-containing buffer at various concentrations, followed by serial dilution. Varying the mixing ratio of carminic acid and albumin affected the extent of histamine release from passively sensitized basophils. Similar basophil histamine release occurred with carminic acid-globulin solutions. These results provide experimental evidence indicating that basophil activation is dependent on hapten (carminic acid) and carrier (protein) interaction.
Anaphylaxis ; Basophils ; Carmine ; Food Additives ; Histamine Release ; Hypersensitivity ; In Vitro Techniques

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.
Administration, Oral ; Anaphylaxis* ; Animals ; Asthma ; Cytokines ; Eosinophils ; Ethanol* ; Flavonoids ; Goblet Cells ; Histamine Release* ; Histamine* ; Hyperplasia ; Immunoglobulin E ; Immunoglobulin G ; Inflammation* ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Lung ; Mast Cells ; Mice ; Ovalbumin ; Ovum ; Plasma ; Rats ; Scutellaria baicalensis* ; Scutellaria* ; Tumor Necrosis Factor-alpha

PURPOSE: Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. METHODS: Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. RESULTS: Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). CONCLUSIONS: U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family.
Allergens* ; Alternaria ; Asthma ; Botrytis ; Diagnosis ; Fatal Outcome ; Fungi ; Histamine Release ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunotherapy ; In Vitro Techniques ; Rhinitis ; Seasons ; Skin Tests ; Spain

PURPOSE: The production of camel heavy-chain antihuman IgE (huIgE) that has the potential to block IgE-FcepsilonRI interaction and histamine release by basophils. METHODS: Camels were immunized with a synthetic loop peptide (SLP) designed in a multiple antigen peptide system (MAPS) forming SLP-MAPS immunogen. Camel polyclonal antibodies (PCAs) were produced, purified, characterized using Protein A & G, ELISA, and SDS-PAGE, and tested for their potency to block passive sensitization and histamine release of human basophils using flow cytometry (FCM) and ELISA, respectively. RESULTS: FCM data indicated that camel conventional (IgG1) and heavy chain antibodies (HCAbs; IgG2, and IgG3) had blocking activities of 43.9%, 72%, and 96.6%, respectively. Moreover, both IgG2 and IgG3 achieved remarkable inhibition rates of 93.98% and 97.05% in histamine release, respectively, whereas the IgG1inhibiting activity was 60.05%. CONCLUSIONS: Camel PCAs produced against SLP-MAPS were capable of blocking the IgE-receptor interaction and the release of histamine by basophils with superiority to HCAbs. These findings may pave the way toward the possible use of camel anti-huIgE HCAbs as blocking antibodies in the treatment of IgE-mediated allergy and asthma.
Antibodies* ; Antibodies, Blocking ; Asthma ; Basophils* ; Camels* ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Histamine Release* ; Histamine* ; Humans* ; Hypersensitivity ; Immunoglobulin E* ; Immunoglobulin G ; Passive Cutaneous Anaphylaxis ; Staphylococcal Protein A

Gastrodia elata Blume is a well-known kind of natural products used as a folk medicine for thousands of years. However, anti-atopic dermatitis-like effects of G. elata Blume had not been evaluated until now. The aim of the present study is to investigate the protective effects of water extract from the roots of G. elata Blume (GE) on 2, 4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions using balb/c mice. Combination treatment of GE (at a dose of 12.5 mg/kg body weight by administrated per os + 0.5 mg/cm2 as ointment to apply on ear and dorsal skin) was significantly inhibited spleen weight, ear thickness, levels of serum immunoglobulin E and number of mast cells, compared with that of 2, 4-dinitrochlorobenzene-included groups without GE. Furthermore, combination application by oral administration plus by ointment of GE significantly inhibited the histamine release from rat peritoneal mast cells. These results suggest that combination treatment of oral administration plus ointment form of GE could be helpful as a potentially natural pharmaceutical treatment on atopic-like dermatitis.
Administration, Oral ; Animals ; Biological Products ; Body Weight ; Dermatitis ; Dermatitis, Atopic ; Ear ; Gastrodia* ; Histamine Release ; Immunoglobulin E ; Immunoglobulins ; Mast Cells ; Medicine, Traditional ; Mice* ; Rats* ; Skin* ; Spleen ; Water

Mast cells are known as effector cells of IgE-mediated allergic responses, but role of mast cells in contact hypersensitivity (CHS) has been considered controversial. In this study, we investigated role of mast cell in trimellitic anhydride (TMA)-induced CHS. The mice were sensitized to TMA on the back and repeatedly challenged with TMA on the left ear at 1-week intervals. The ear after challenge showed biphasic responses. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of early and late phase reactions in proportion to the frequency of TMA challenges in C57BL/6 mice. In late phase reaction, peak of ear response by single challenge showed at 24 hours after challenge, but the peak by repeat challenges at 8 hours after the last challenge. Number of mast cells and eosinophils per unit area increased in proportion to frequency of TMA challenges. However, mast cell-deficient WBB6F1/J-Kit(W)/Kit(W-v) mice developed the late phase reaction without the early phase reaction. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of ear response and the infiltration of eosinophils. The magnitude of these responses observed according to the frequency of the TMA challenge in mast cell-deficient WBB6F1/J-Kit(W)/Kit(W-v) mice was significantly lower than that in C57BL/6 mice. Also TMA elicited mast cell degranulation and histamine release from rat peritoneal mast cells in a concentration-dependent manner. Conclusively, TMA induces the early and late phase reactions in CHS, and mast cells may be required for TMA-induced CHS.
Animals ; Dermatitis, Contact* ; Ear ; Eosinophils ; Histamine Release ; Mast Cells* ; Mice ; Rats

PURPOSE: To evaluate the effect of olopatadine and ketotifen to stabilize mast cells using human umbilical cord blood-derived mast cells (hCBMCs). METHODS: Using cultured hCBMCs, we divided the cells into the Ketotifen fumarate treatment group, the Olopatadine hydrochloride treatment group, the positive control group, and the negative control group. The histamine release inhibition rate was then observed. RESULTS: Ketotifen and olopatadine both showed the highest inhibition rate of histamine release at a concentration of 10(-3.5)M (Ketotifen, 48% and Olopatadine, 62%). The histamine release inhibition rate of olopatadine was 28% at a concentration of 10(-5.5)M, but ketotifen demonstrated a low histamine release inhibition rate at the same concentration. Ketotifen and olopatadine showed no histamine release inhibition at concentrations of 10(-2)~10(-2.5)M, and 10(-6)M. CONCLUSIONS: Ketotifen and olopatadine demonstrated histamine inhibition in the concentration range of 10(-3) to 10(-5)M. Olopatadine showed a slightly stronger response than ketotifen in the inhibition of histamine release.
Histamine ; Histamine Release ; Humans* ; Ketotifen* ; Mast Cells* ; Umbilical Cord* ; Olopatadine Hydrochloride

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.
Adult ; Alleles ; Anaphylaxis* ; Asthma ; Basophil Degranulation Test ; Basophils ; Codeine* ; Constipation ; Cough ; Cytochrome P-450 CYP2D6 ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Eating ; Euphoria ; Female ; Food Hypersensitivity ; Genotype ; Histamine ; Histamine Release ; Humans ; Nausea ; Respiratory Tract Infections ; Rhinitis ; Seafood ; Skin ; Sleep Stages ; Thorax ; Urticaria

Factors that can induce the release of histamine from basophils have been studied for more than 30 years. A protein termed histamine-releasing factor (HRF) was purified and molecularly cloned in 1995. HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF-like activities were found in bodily fluids during the late phase of allergic reactions, implicating HRF in allergic diseases. However, definitive evidence for the role of HRF in allergic diseases has remained elusive. On the other hand, we found effects of monomeric IgE on the survival and activation of mast cells without the involvement of a specific antigen, as well as heterogeneity of IgEs in their ability to cause such effects. The latter property of IgE molecules seemed to be similar to the heterogeneity of IgEs in their ability to prime basophils in response to HRF. This similarity led to our recent finding that ~30% of IgE molecules can bind to HRF via their Fab interactions with two binding sites within the HRF molecule. The use of peptide inhibitors that block HRF-IgE interactions revealed an essential role of HRF to promote skin hypersensitivity and airway inflammation. This review summarizes this and more recent findings and provides a perspective on how they impact our understanding of allergy pathogenesis and potentially change the treatment of allergic diseases.
Asthma* ; Basophils ; Binding Sites ; Clone Cells ; Hand ; Histamine ; Histamine Release ; Hypersensitivity* ; Immunoglobulin E ; Immunoglobulins* ; Inflammation ; Interleukin-13 ; Interleukin-4 ; Mast Cells ; Population Characteristics ; Skin