Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.

Involvement of the IgE-basophil system and mild complement activation in haemophilia B with anti-factor IX neutralizing antibodies and anaphylaxis.

INTRODUCTION: Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. AIM: To investigate biomechanisms of FIX hypersensitivity. METHODS: A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure. Anti-FIX IgE and IgG antibodies and markers of complement activation (C5b9, C3d and iC3b) were measured in plasma, the last also after FIX infusion. Ten healthy children served as controls. RESULTS: The patient who developed anti-FIX inhibitors and anaphylaxis had a nonsense mutation in FIX gene (p.Arg298Stop) and, compared to controls, had higher plasma levels of specific anti-FIX IgE (2.285 vs 0.084 OD492 nm ), with marked LTC4 release from his FIX-stimulated basophils (519.8 vs 39.9 pg/mL). Further, he had higher plasma levels of anti-FIX IgG of all the four subclasses (total IgG 1.180 vs 0.120 OD492 nm ) with FIX neutralizing activity (1.5 BU); mild complement activation occurred during FIX-induced anaphylaxis (C5b9 increased from 258.5 to 351.1 ng/mL). The same parameters were normal in the two patients who tolerated FIX infusion. CONCLUSION: In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies.

Eosinophil cationic protein levels parallel coagulation activation in the blister fluid of patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease due to autoantibodies against two hemidesmosomal antigens, namely BP180 and BP230, and characterized by coagulation activation both at cutaneous and systemic levels. Skin-infiltrating eosinophils contribute to bulla formation and, upon activation, are supposed to initiate the coagulation cascade. OBJECTIVE: The aim of this study was to investigate whether the activation of eosinophils and coagulation are linked in BP. METHODS: We evaluated the correlation between eosinophil cationic protein (ECP) levels and concentrations of the prothrombotic markers F1 + 2 and D-dimer in blister fluid and blood samples of 30 BP patients. Thirty healthy subjects were used as normal controls. RESULTS: ECP, F1 + 2 and D-dimer plasma levels were significantly higher in BP patients than in normal subjects. A significant correlation was found between ECP plasma levels and blood eosinophil count (r = 0.54, P = 0.002). F1 + 2 plasma levels positively correlated with disease severity, expressed as the percentage of body surface area involved (r = 0.36, P = 0.048). A striking increase in ECP (288.8 ± 45.2 ng/mL), F1 + 2 (31 409.9 ± 2929.4 pmol/L) and D-dimer levels (342 798.3 ± 44 206 ng/mL) was found in blister fluid from BP patients. In blister fluid, ECP levels were significantly higher than in peripheral blood (P < 0.0001) and were positively correlated with the levels of both F1 + 2 (r = 0.4, P = 0.02) and D-dimer (r = 0.5, P = 0.0045). CONCLUSIONS: ECP levels are strikingly elevated in blister fluids from BP patients and correlate with markers of coagulation activation, supporting the view that eosinophils initiate the coagulation cascade at skin level.

Serum eotaxin levels in patients with chronic spontaneous urticaria.

Eotaxin is a potent agonist for CC chemokine receptor 3 that can attract eosinophils at sites of inflammation. Given the potential role of eosinophils in chronic spontaneous urticaria (CU), we measured serum eotaxin levels together with C-reactive protein in 100 CU patients who were characterized according to autologous serum skin test (ASST) and disease severity. Serum eotaxin concentration was significantly higher in CU patients (median 140.1 pg/ml, range 33.7-718.7 pg/ml) than in 45 healthy controls (median 108.9 pg/ml, range 45.5-409.4 pg/ml) (p = 0.032) Serum eotaxin concentration was not significantly different in ASST-positive and ASST-negative patients as well as in patients with different urticaria activity scores. However, eotaxin levels tended to be higher in patients with intense symptoms. In the 7 patients observed during CU exacerbation and during remission, eotaxin serum levels tended to decrease during remission, although statistical significance was not reached (median concentration decreased from 170.0 pg/ml to 123.8 pg/ml). CRP levels were not significantly different in CU patients and healthy subjects, although there was a trend towards higher levels in the former population. Furthermore, in the 7 patients observed during CU exacerbation and during remission, CRP levels decreased significantly during remission (median concentration dropped from 4.1 microg/ml to 0.7 microg/ml, p = 0.015). No significant correlation was found between eotaxin and CRP serum levels. These findings indicate that serum eotaxin levels are increased in CU patients, although they do not reflect strictly disease activity. A role for eotaxin in eosinophil attraction and activation in CU can be envisaged.

Different rates of autoreactivity in patients with recurrent idiopathic angioedema associated or not with wheals.

BACKGROUND: The pathophysiology and triggers of idiopathic nonhistaminergic angioedema are unclear. This study aimed to assess autoreactivity in recurrent idiopathic angioedema associated or not with wheals. METHODS: The study population comprised 19 patients with recurrent idiopathic nonhistaminergic angioedema without wheals, 38 patients with angioedema and chronic urticaria (CU), and 52 patients with CU without angioedema. Twenty healthy individuals served as controls. Autoreactivity was evaluated in vivo using the autologous serum skin test (ASST) and in vitro by measuring serum-induced basophil histamine release (BHR). RESULTS: ASST results were negative in all patients with idiopathic angioedema without wheals and in healthy controls and positive in 29 of the 38 patients with angioedema and CU (76.3%) and in 26 of the 52 patients with CU without angioedema (50%) (P < .0001 for both CU groups). BHR was negative in the healthy controls and positive in 2 of the 19 patients with idiopathic angioedema without wheals (10.5%), in 18 of the 38 patients with angioedema and CU (47.3%) (P < .0001), and in 11 of the 52 patients with CU without angioedema (21.1%) (P < .03). CONCLUSION: The different rates of autoreactivity observed in patients with idiopathic nonhistaminergic angioedema without wheals and in patients with CU either with or without angioedema suggest that these disorders have a different pathophysiology. The failure to detect circulating vasoactive factors and histamine-releasing autoantibodies explains why H1 antihistamines are scarcely effective in most patients with idiopathic angioedema without wheals. However, they represent the cornerstone of CU treatment.

Plasma levels of matrix metalloproteinase-9 in chronic urticaria patients correlate with disease severity and C-reactive protein but not with circulating histamine-releasing factors.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an endopeptidase produced by many inflammatory cells that has been found in increased amounts in plasma from patients with chronic urticaria (CU). OBJECTIVE: To evaluate plasma levels of MMP-9 and its tissue inhibitor of metalloproteinase-1 (TIMP-1) in CU patients in relation with disease severity, C-reactive protein (CRP) and circulating histamine-releasing factors. METHODS: Fifty-two consecutive CU patients were included in the study and disease activity was graded from 0 to 3. Plasma MMP-9, TIMP-1 and CRP levels were measured by enzyme immunoassays. Circulating histamine-releasing factors were assessed using in vivo (autologous serum skin test) and in vitro (basophil histamine release) tests. Seven CU patients were studied both during active disease and during remission. Thirty healthy subjects were used as normal controls. RESULTS: Plasma levels of MMP-9, TIMP-1 and CRP were significantly higher in CU patients than in healthy controls (P=0.0001, 0.003 and 0.005, respectively) and a trend towards a higher MMP-9/TIMP-1 molar ratio was found (P=0.051). A significant correlation was found between plasma MMP-9 levels and urticaria severity score (r=0.48, P<0.0001). CRP levels correlated with MMP-9 levels (r=0.37, P=0.008) and CU severity score (r=0.52, P=0.0001), but not with TIMP-1 (r=0.13) concentrations. MMP-9, TIMP-1 and CRP plasma levels and MMP-9/TIMP-1 molar ratio did not differ in patients either with or without an evidence of circulating histamine-releasing factors. Seven patients evaluated during remission showed a significant reduction of MMP-9 and CRP plasma levels. CONCLUSION: Plasma levels of MMP-9 and its inhibitor TIMP-1 are increased in CU patients. MMP-9 levels are associated with disease severity and CRP levels, but not with skin reactivity to autologous serum and with circulating histamine-releasing factors. These findings suggest that in CU there is an ongoing inflammatory process independent of the presence of circulating histamine-releasing factors.

Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticaria.

BACKGROUND: Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU. METHODS: Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F(1+2) were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP). RESULTS: Plasma VEGF concentrations were higher in CU patients (8.00 +/- 0.90 pmol/l) than in controls (0.54 +/- 0.08 pmol/l) (P = 0.0001) and tended to parallel both the severity of CU and to correlate with F(1+2) levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients (P = 0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF (P = 0.002) that colocalized with ECP, a classic eosinophil marker. CONCLUSIONS: VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin.

Antihistamines do not inhibit the flare induced by the intradermal injection of autologous plasma in chronic urticaria patients.

BACKGROUND: There is some evidence suggesting that factors other than autoantibodies to FceRI or IgE and histamine released from mast cells may play a role in skin autoreactivity that characterizes many patients with chronic urticaria (CU) and, possibly, in the pathogenesis of this disease. OBJECTIVE: The effect of antihistamine treatment on autologous plasma skin test (APST) in patients with CU was assessed. METHODS: 24 patients with CU underwent autologous plasma skin test (APST) as well as SPT with histamine 10 mg/ml while taking antihistamines. In 6 cases the same tests had been carried out also before the start of antihistamine treatment. Plasma levels of D-dimer, prothrombin F 1+2 fragment, and vascular endothelial growth factor (VEGF) were measured in 21 patients. RESULTS: 21/24 (87%) patients showed a large flare on APST while taking antihistamines while the skin reaction to histamine 10 mg/ml was abolished or negligible. Little difference in the autologous plasma-induced flare was seen before and after the start of cetirizine therapy in 6 cases, whereas the drug exerted a marked effect on the histamine SPT as well as on the autologous plasma-induced wheal. The APST-induced flare was not associated with patients' response to antihistamine. Plasma levels of VEGF, prothrombin F 1+2 fragment, and D-dimer were increased in plasmas from 8, 9, and 2 patients, respectively. CONCLUSIONS: Factors other than histamine are probably involved in the flare following APST in CU; such factors might play a pathogenic role particularly in patients not responding to standard antihistamine treatments.

Novel clinical and serological aspects in non-allergic asthma.

BACKGROUND: We have recently observed that skin reactivity to autologous serum injection is common in patients with non-allergic asthma. However, clinical significance of skin reactivity to autologous serum remains to be defined. OBJECTIVE: To evaluate the possible relation between skin reactivity to autologous serum and clinical and laboratory characteristics in a series of patients with non-allergic asthma. METHODS: Fifty-five patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using basophils from a normal donor. Clinical and laboratory characteristics including peripheral blood eosinophilia, antinuclear antibodies and total IgE concentration were evaluated. As control, ASST was performed in 10 allergic asthmatic patients, 10 patients with allergic rhinitis and 10 normal subjects. RESULTS: ASST was positive in 29/55 non-allergic asthmatics (53%), whereas it was negative in all 30 control subjects (P<0.001). The sera of 6 out of 51 patients induced in vitro histamine release from autologous basophils. The sera from two patients induced histamine release from membrane IgE-stripped basophils. A significant predominance of female sex (83%) and a high incidence of antinuclear antibodies (ANA) positivity (55%) were found among ASST-positive patients. CONCLUSION: These findings indicate that ASST is positive in about half patients with non-allergic asthma and that a proportion of patients (16%) has functional evidence of circulating histamine-releasing factors. In addition, predominance of female sex and frequent ANA positivity are in line with an autoimmune basis of non-allergic asthma.

Serum interleukin-18 in patients with chronic ordinary urticaria: association with disease activity.

Interleukin (IL)-18 is a pleiotropic cytokine, which may play a role in autoimmune and allergic disorders. Serum IL-18 levels were measured in 34 patients with chronic ordinary urticaria (COU) and 17 normal subjects. In vivo and in vitro assays for histamine-releasing factors, an autologous serum skin test (ASST) and a basophil histamine release assay were also performed for all patients with COU. Serum IL-18 concentration was not significantly different between patients with COU and normal subjects (mean+/-standard error of the mean 246.47+/-18.40 pg/mL vs. 213.88+/-22.24 pg/mL), and no significant difference was found between ASST-positive and ASST-negative patients. However, in ASST-positive patients, IL-18 levels paralleled clinical severity scores and showed a tendency to correlate with in vitro histamine release. The increased IL-18 levels in the ASST-positive patients with most active chronic urticaria may reflect stronger immune system activation and possibly an involvement of IL-18 as a direct histamine-releasing factor.

Detection of serum histamine-releasing factors in a patient with idiopathic anaphylaxis and multiple drug allergy syndrome.

We describe the case of a 30-year-old woman who reported several episodes of anaphylaxis with angioedema and relapsing urticaria. Some events were related to nonsteroidal anti-inflammatory drug intake and one episode followed alcohol ingestion, but in most cases no triggers could be identified. Specific immunoglobulin E determination was negative for food and drug allergens, C3 and C4 were in the normal range, C1 inhibitor was slightly reduced and serum tryptase was undetectable. In vivo autologous serum skin test and in vitro basophil histamine release assay were positive indicating the presence of circulating histamine-releasing factors. When oral tolerance tests were performed, only doxycycline was tolerated whereas levofloxacin, clarithromycin, nimesulide and tramadol caused mild urticaria. Premedication with cetirizine allowed the patient to tolerate levofloxacin, clarithromycin and nimesulide. The demonstration of circulating histamine-releasing factors in a patient with idiopathic anaphylaxis and multiple drug allergy syndrome provides a new mechanistic insight and might open the way to new therapeutic approaches.

Autologous serum skin test reactivity in patients with non-allergic asthma.

BACKGROUND: Inflammatory alterations of respiratory airways have been found in patients with non-allergic asthma, but the triggering event has not been defined. An autoimmune activation of inflammatory cells has been hypothesized. OBJECTIVE: To evaluate whether histamine-releasing factors are present in sera from non-allergic asthmatics. METHODS: Twenty-four patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using autologous basophils as well as basophils from normal donors. Twenty-seven subjects with respiratory allergy and three normal subjects were chosen as control. RESULTS: ASST was positive in 14/24 non-allergic asthmatics (58%) whereas it was negative in all 30 control subjects (P<0.001). The serum of only one ASST-positive patient out of 12 (8.4%) induced in vitro histamine release from autologous basophils. The serum from another ASST-positive patient induced histamine release from membrane IgE-stripped autologous basophils. Sera from either non-allergic asthmatics or from control subjects did not provoke significant histamine release from basophils from three normal donors. CONCLUSION: Skin reactivity to autologous serum is common among non-allergic asthmatics, indicating the presence of circulating histamine-releasing factors. However, only in a minority of patients in vitro functional evidence of histamine-releasing autoantibodies (anti-FcepsilonRI or anti-IgE) was obtained. The presence of circulating histamine-releasing factors might contribute to initiation/maintenance of inflammation in respiratory airways of non-allergic asthmatics.

No evidence of increased serum substance P levels in chronic urticaria patients with and without demonstrable circulating vasoactive factors.

The neuropeptide substance P is a possible candidate as histamine-releasing factor in some patients with chronic ordinary urticaria (COU), particularly in those with evidence of a nonautoantibody circulating histamine-releasing factor. In this study, serum substance P levels were measured by enzyme immunoassay in 117 COU patients, 40 atopic subjects and 24 normal subjects. In vivo and in vitro assays for histamine-releasing factors, autologous serum skin test (ASST) and basophil histamine release (BHR) assay, respectively, were performed in all COU patients. Mean serum substance P concentration was not significantly different in COU patients and in normal subjects; however, significantly higher levels were detected in atopic subjects than in COU patients (P < 0.003). ASST and BHR assays allowed us to distinguish different subsets of COU patients. Mean serum substance P concentration did not vary significantly in the different subsets of patients. Nevertheless, interestingly three patients with positive ASST and negative BHR assay showed very high substance P levels. These results suggest that substance P does not play an important role as histamine-releasing factor in COU in general but only in occasional patients in whom it might act as a trigger of urticarial symptoms.

Assessment of histamine-releasing activity of sera from patients with chronic urticaria showing positive autologous skin test on human basophils and mast cells.

BACKGROUND: All previous studies agree that only a proportion of sera from patients with chronic urticaria (CU) positive on the autologous serum skin test (ASST) are able to induce histamine release in vitro. A non-specific release of bradykinins during clotting of blood samples has been suggested; however, ASST seems rather specific and some data point to the existence of a mast cell-specific histamine-releasing factor. OBJECTIVE: To assess whether, and to what extent, the use of both human basophils and mast cells increases the sensitivity of in vitro histamine release assays (HRAs) in ASST-positive patients with CU. METHODS: The histamine-releasing activity of sera from 93 patients with CU selected on the basis of strong skin reactivity on ASST was assessed in vitro on basophils from 1 (n=86), 2 (n=31), or 3 (n=20) normal donors, and on mast cells from 1 (n=3), 2 (n=3), or 3 (n=87) normal donors. RESULTS: Sera from 88/93 (95%) patients induced significant histamine release from mast cells or basophils on at least one HRA. 76/93 (82%), 45/90 (50%), 22/80 (28%), and 6/12 (50%) sera were able to induce significant histamine release from cells of 2/5, 3/5, 4/5 and 5/5 donors, respectively. CONCLUSION: Sera from nearly all ASST-positive patients with CU are able to induce histamine release in vitro. However, the serum from each single patient seems to show its maximal activity on autologous mast cells in vivo, and functional in vitro tests show much variability and seem less sensitive than ASST in the detection of patients with histamine-releasing factors in their blood.

Prevalence and risk factors for latex allergy: a cross sectional study on health-care workers of an Italian hospital.

OBJECTIVES: The aim of this study was to determine prevalence and risk factors for latex hypersensitivity among health care workers (HCW) of an Italian general hospital. METHODS: 1747 HCW of the Ospedale Maggiore Policlinico of Milan were asked to fill in a questionnaire regarding latex-related manifestations (LRM) and personal medical history, and latex-specific IgE were measured by RAST-Cap system. RESULTS: 672 out of 1747 HCW (38.4%) answered to the questionnaire. LRM were reported by 168 out of 672 HCW (25%). The most common manifestation was hand dermatitis and itching (86.3%), followed by urticaria (3.5%) and respiratory symptoms (2.9%). Among the HCW with LRM, 75 (44.6%) reported a personal history of atopy and 24 (14.3%) reported oral allergy syndrome. most commonly related to kiwi, tomato, peach and melon/watermelon. Latex-specific IgE were found in 62 out of 1747 HCW (3.6%). Among the subjects answering the questionnaire, latex-specific IgE positivity was associated with occurrence of LRM (most commonly allergic contact dermatitis) and a longer professional exposure. The risk of latex IgE sensitisation was four times higher in HCW reporting atopic manifestations than in HCW without atopic disorders. Prevalence of LRM and latex-specific IgE was significantly higher among workers of auxiliary staff than among other job categories. The highest latex-specific IgE levels were found in subjects with severe latex-related symptoms and a personal history of atopy. CONCLUSIONS: A high prevalence of LRM was found among the HCW of an Italian general hospital, although a true latex sensitisation was detected only in a minority of cases. Members of the auxiliary staff, who wear latex gloves for several hours a day, had an increased prevalence of LRM and latex sensitisation. Atopy was a major risk factor for LRM and latex-specific IgE response.

Chronic autoreactive urticaria at six years of age.

A case of chronic urticaria in a child 6 years old is described. The strong skin reactivity upon intradermal injection of autologous serum suggested an autoreactive pathogenesis; however, patient's serum was unable to induce histamine release from basophils in-vitro, indicating the presence of a histamine-releasing factor specific for mast cells, and possibly other than an anti-FcepsilonRI or anti-IgE antibody. Intradermal test with autologous serum may be useful in revealing the autoreactive nature of chronic urticaria and can avoid a frustrating search for other causes of the disease. In children presenting with chronic or recurrent urticaria the diagnostic workup should include the autologous serum skin test.

Serum histamine-releasing activity in a patient with idiopathic pulmonary haemosiderosis

Background: idiopathic pulmonary haemosiderosis (IPH) is a rare disorder characterized by intermittent, diffuse alveolar bleeding. The pathogenesis of the diseases is unclear, although an association with milk or gluten hypersensitivity has been described, and an immune-mediated damage of alveolar capillaires has been suggested. A previous report showed the release of histamine after cow's milk intake in a newborn with cow's milk intolerance and IPH. Methods and results: here, we report the detection of serum histamine-releasing activity (HRA) in a 30-year-old woman with IPH. The serum taken during an active phase of the disease induced histamine release from basophils of two normal donors; conversely, when the patient was receiving prednisone and azathioprine, and the disease was in remission, the serum HRA was reduced. Serum fractions with a MW lower than 100 kDa displayed an enhanced HRA; in contrast, serum fractions with MW above 100 kDa were not able to induce histamine release, suggesting that the activity was due to a cytokine and not to an immunoglobulin. Conclusions: the detection of serum HRA provides further evidence that the immune system is activated in the course of IPH and supports an immunologic basis for the alveolar capillary damage, which is responsible for alveolar bleeding (AU)

Antecedentes: la hemosiderosis pulmonar idiopática (IPH) es un raro trastorno caracterizado por un sangrado alveolar intermitente y difuso. La patogénesis de esta enfermedad no es clara, no obstante ha sido descrita una asociación con hipersensibilidad a la leche o al gluten, sugiriendo un daño en los capilares alveolares inmunomediado. Una previa comunicación señala la liberación de histamina después del consumo de leche de vaca en un recién nacido con intolerancia a la leche de vaca y IPH. Métodos y resultados: a continuación, referimos la detección de la actividad de liberación de histamina (HRA) en el suero de una mujer de 30 años con IPH.El suero tomado durante la fase activa de la enfermedad indujo la liberación de histamina de los basófilos de dos donantes normales; inversamente, cuando el paciente recibió prednisona y azatioprina, y la enfermedad estaba en remisión, la HRA del suero se redujo. Las fracciones del suero con peso molecular (MW) por debajo de 100 kDa presentaron un aumentado HRA; en contraste, las fracciones del suero con MW por encima del 100 kDa no fueron capaces de inducir la liberación de histamina, sugiriendo que la actividad era debida a citocinas y no a inmunoglobulinas. Conclusiones: la detección en el suero de HRA provee ulteriores evidencias que el sistema inmune es activado en el curso de IPH y sostiene una base inmunológica del daño capilar alveolar, responsable del sangrado alveolar (AU)

NSAID intolerance in chronic idiopathic urticaria: A study of its relationship with histamine-releasing activity of patients' sera.

BACKGROUND: about one fourth of patients with chronic idiopathic urticaria (CIU) experience flares of hives after taking chemically unrelated nonsteroidal anti-inflammatory drugs (NSAID). The reasons for such intolerance are still elusive. OBJECTIVE: this study aimed to investigate NSAID intolerance in patients with CIU in view of the in vivo and in vitro histamine releasing activity of their sera. METHODS: 117 adults (M/F 41/76) with CIU underwent intradermal test with autologous serum, and the ability of their sera to induce histamine release from normal blood donors was evaluated. NSAID intolerance was ascertained by careful interview. RESULTS: overall, 32/117 (27 %) patients reported NSAID intolerance. The prevalence on NSAID intolerance did not differ in the three subgroups: negative on both in vivo and in vitro tests (9/36; 25 %), positive or intradermal test but negative on basophil histamine release assay (16/58; 28 %), or positive on both in vivo and in vitro tests (7/23; 30 %). CONCLUSION: in patients with CIU intolerance to NSAID does not depend on the mechanism of histamine release.