Serum total tryptase levels are increased in patients with active chronic urticaria

Background We have demonstrated previously mast cell histamine release upon incubation with chronic urticaria (CU) sera, presumably by degranulation. Objective To explore total and mature tryptase in order to assess whether any increase in total tryptase levels is due in part to mast cell degranulation or to mast cell burden. We also wanted to explore differences between the autoimmune groups called idiopathic (serum unable to activate basophils), and to correlate total and mature tryptase levels with different urticaria features. Methods We measured total and mature tryptase serum levels in 81 CU patients, 16 atopic donors and 21 healthy control sera. We assessed autoimmunity by measuring the CD63 expression in normal basophil donors upon incubation with CU sera. Results We found significantly higher levels of total tryptase in the sera of CU patients (6.6 ±4.1 μg/L) than in sera from healthy non‐atopic subjects (4.4 ±2.8 μg/L) and from atopic subjects (4.5 ±1.7 μg/L). Mature tryptase levels were undetectable (<1 ng/mL). Total tryptase levels in the autoimmune urticaria group were significantly higher (9.8 ±5.4 μg/L) than the idiopathic urticaria group (4.4 ±2.2 μg/L). A significant difference in total tryptase was found between symptomatic patients (7.3 ±4.1 μg/L) compared with asymptomatic ones (5.7 ±4.1 μg/L) at the time of venesection. No difference was found in mature tryptase levels either. Conclusion Total elevated tryptase levels are not accompanied by an elevated mature tryptase levels, as might be expected if the serum levels reflected mast cell degranulation. Cite this as: M. Ferrer, J. M. Nuñez‐Córdoba, E. Luquin, C. E. Grattan, J. M. De la Borbolla, M. L. Sanz, L. B. Schwartz, Clinical & Experimental Allergy, 2010 (40) 1760–1766.     

Specific immunoglobulin E for staphylococcal enterotoxins in nasal polyps from patients with aspirin-intolerant asthma

BACKGROUND: Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin-intolerant asthma (AIA) than aspirin-tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown. OBJECTIVE: We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects. METHODS: Fifteen AIA subjects with positive responses to lysine-aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL-5, mast cell tryptase, soluble IL-2 receptors (sIL-2R), total IgE, and specific IgE for SEA and SEB. RESULTS: ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (P < 0.02), with no significant differences in tryptase, IL-5 or sIL-2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P = 0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL-5, but not those of tryptase or sIL-2R. CONCLUSION: These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.     

Increased mast cell tryptase in sudden infant death — anaphylaxis,hypoxia or artefact?

BACKGROUND: Increased concentrations of mast cell tryptase in post mortem blood have frequently been observed in sudden infant deaths but the cause of this has not yet been clarified. OBJECTIVE: The aim was to evaluate factors (immunological, morphological and anamnestic data) behind the observed increase in mast cell tryptase in sudden infant deaths with elevated tryptase. METHODS: Mast cell tryptase and total immunoglobulin (Ig) E were measured in post mortem sera from 44 infants younger than 1.5 years. Radioallergosorbent tests were performed for possible allergens (mixture for relevant food allergens, Phadiatop and latex). IgG subclasses, IgM, and complement factors (C3, C4 and factor B) were measured with radial immunodiffusion. Mast cells, labelled with antibodies against mast cell tryptase, were counted in the lungs and heart. The circumstances of death and medical history of the deceased infant and family were obtained through police and hospital records. RESULTS: In 40% of the SIDS cases tryptase was elevated (>10 microg/L). Total IgE in serum was increased in 33% compared with clinical reference values but showed no association with mast cell tryptase. RAST tests were positive in three cases. In one of these cases both tryptase and total IgE were elevated. The only variable that was associated with high tryptase values was prone position at death (P < or = 0.05 ). Allergy or asthma in the family were alleged in 50% of the cases, but was not associated with elevated tryptase or IgE. Children with elevated total IgE also displayed high concentrations of IgG1 and IgG2. Infants who died in the spring had significantly higher IgE than the others (P < or = 0.05). CONCLUSION: The results do not support the hypothesis that the elevated tryptase concentrations in sudden infant death are caused by allergy. The association between prone position at death and elevated tryptase could hypothetically be explained by mast cell degranulation due to, for example, a hypoxic stimulus in these infants.     

Chronic urticaria: a disease at a crossroad between autoimmunity and coagulation

Chronic urticaria (CU), defined as recurrence of wheals with or without angioedema for more than 6 weeks, is a quite common disease that may severely worsen the quality of life. Studies carried out during the last 2 decades have demonstrated an autoimmune pathogenesis mediated by functionally active autoantibodies to the high affinity IgE receptor (FcepsilonRI) or to IgE which are able to induce histamine release from basophils and mast cells. However, such mechanism can be detected in less than 50% of patients only. The present article reviews recent findings showing an additional pathogenic mechanisms in CU patients: activation of the coagulation cascade resulting in thrombin production. Thrombin is a serine protease which may play a key role in urticaria, being able to induce edema through an increase in vascular permeability, mast cell activation and degranulation, and to induce the production of the anaphylotoxin C5a. Such mechanism seems to be active in the majority of CU patients, however their relationship with anti-FcepsilonRI or anti-IgE autoantibodies is still matter of research.     

EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA‐DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new ‘gold standard’ for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.     

Elevated serum B-cell activating factor in patients with chronic urticaria

The B and T cells abnormalities that have been described among CU patients, lend support to its regard as an autoimmune disease. In this study we compared serum B-cell activation factor (BAFF) levels in 46 CU patients to 24 healthy controls and evaluated a possible association between elevated serum BAFF in CU patients and the presence of autologous serum skin test, anti-thyroid antibodies, antinuclear antibodies, high total IGE levels, and urticaria disease severity. We found that serum BAFF levels is elevated statistically significant in CU patients compared to healthy control (1228±342 pg/ml vs. 758±313 pg/ml, P<0.0001). CU patients with severe disease activity had significantly higher serum BAFF levels compared to patients with mild CU (1394.6±299.6 vs. 1097.6±221.3, P=0.0008). No association was found between the presence of positive autologous serum skin test, anti-thyroid antibodies or antinuclear antibodies or high levels of total IgE and serum BAFF levels in CU Patients. We conclude that CU patients have higher levels of serum BAFF which associate with disease severity.     

Autoantibodies in chronic idiopathic urticaria and nonurticarial systemic autoimmune disorders

BackgroundChronic idiopathic urticaria (CU) has been associated with other autoimmune diseases and basophil-activating autoantibodies to FcεRI or IgE. It is unknown whether patients with systemicautoimmune diseases have a similar prevalence of these autoantibodies.ObjectiveTo compare the prevalences of basophil-activating autoantibodies (elevated CU Index) in patients with CU, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Clinical characteristics and laboratory studies were examined for an association with the CU Index.MethodsAdult patients, 27 with CU, 27 with RA, and 26 with SLE, and 20 healthy controls were compared on the basis of the CU Index panel, anti-IgE, and antithyroid antibodies.ResultsThe CU Index values were significantly higher in the CU group when compared with the RA group but not when compared with the SLE group. 33% of CU, 23% of SLE, 3.7% of RA, and 15% of controls had apositive CU Index. Elevated antithyroid antibody levels did not correlate with a positive CU Index in any of the groups. An elevated CU Index in the SLE group was not associated with age, sex, ethnicity, disease severity, or history of atopy.ConclusionThe CU Index values were elevated in patients with CU and SLE. The presence of these autoantibodies did not correlate with disease activity or presence of thyroid antibodies. Functional autoantibodies may not be specific for chronic idiopathic urticaria, and their role in nonurticarial systemic autoimmune diseases requires further investigation.     

Elevated serum concentrations of β-tryptase, but not α-tryptase, in Sudden Infant Death Syndrome (SIDS). An investigation of anaphylactic mechanisms

BACKGROUND: Sudden Infant Death Syndrome, (SIDS) or cot death, remains the most common category of post-perinatal death in the UK. By definition, the cause of death is unknown, but a long-standing theory is that some of these deaths could be the result of anaphylaxis. OBJECTIVE: To investigate the potential contribution of anaphylactic mechanisms to deaths in infancy by determining relative levels of alpha- and beta-tryptases and both total and allergen-specific IgE in sera from groups of infants whose deaths were attributed to SIDS or to other causes. METHODS: Serum samples were collected at the time of post-mortem examination from infants whose death was classed as SIDS (n = 40) and from a comparison group in which cause of death had been established (n = 32). Serum tryptase concentrations were measured with a radioimmunoassay with monoclonal antibody G5 which detects primarily beta-tryptase or an ELISA with antibody AA5 which has equal sensitivity for alpha- and beta-tryptases. Levels of total IgE and IgE specific for casein, beta-lactoglobulin, house dust mite and moulds were determined. RESULTS: Analysis of the results of the two assays for tryptase indicated that levels of the beta-like tryptase (the form secreted on anaphylactic degranulation) were significantly higher in serum from infants with SIDS compared with those whose death was explained. There was no evidence for an increase in serum levels of alpha-tryptase (the variant secreted constitutively from mast cells). Total levels of serum IgE did not differ between the two groups and, reflecting the low circulating IgE concentrations in infancy, an elevation in IgE specific for the panel of allergens was not detected. CONCLUSIONS: In a proportion of SIDS victims there may be increased serum levels of beta-like tryptase, a marker for anaphylaxis. The failure to detect an increase in alpha-tryptase would suggest that mast cell hyperplasia is not a feature of cot death. The nature of the inciting agents remains unclear, but anaphylaxis deserves serious consideration as a possible cause of sudden death in infancy.     

血清肥大细胞羧肽酶与支气管哮喘的相关性研究

目的：检测支气管哮喘患者外周血中肥大细胞羧肽酶的含量,研究其与哮喘患者FEV 1(%)、IgE的关系,探讨其在支气管哮喘发病机制中的作用。方法：35例临床确诊为中重度持续性支气管哮喘患者作为病例组,均行肺功能及IgE水平检测,依据血清IgE水平将支气管哮喘患者分为IgE升高组（n=20）和IgE正常（n=15）。另外,选取22名健康者作为对照组,采用ELISA法检测受试者血清肥大细胞羧肽酶水平。比较支气管哮喘患者与健康者血清中肥大细胞羧肽酶水平;分析血清肥大细胞羧肽酶水平与IgE及肺功能的相关性。结果：IgE升高组患者血清肥大细胞羧肽酶水平明显高于IgE正常组（P＜0.05）;支气管哮喘急性发作期患者血清肥大细胞羧肽酶水平明显高于健康对照组（P＜0.05）;另外,哮喘急性发作期患者血清肥大细胞羧肽酶水平与患者FEV(%)呈明显的负相关;缓解期血清肥大细胞羧肽酶水平与FEV-1(%)无相关性（r=-0.421, P=0.012;r=-0.284,P=0.099）。结论：血清肥大细胞羧肽酶可能参与了支气管哮喘急性发作的气道炎症反应。     

Soluble interleukin-2 receptors and autoantibodies in the serum of healthy elderly individuals

Recently, we reported an increased incidence of various autoantibodies in a healthy elderly population (Group A, 64 subjects). Presently we examined whether there is variability in the expression of the age-associated immunological aberrations between different geriatric populations by extending our observations in another healthy elderly population (Group B, 119 subjects). We also determined the serum levels of soluble IL-2 receptors (sIL-2R) attempting to define the activation status of the immune system during senescence. Compared to non-elderly controls, healthy elderly individuals exhibited a significantly higher incidence of autoantibodies as well as significantly higher levels of sIL-2R in serum (p less than 0.001), the latter possibly suggesting the occurrence of lymphocytic activation during the ageing process. The overall prevalence of autoantibodies was statistically associated with the presence of raised sIL-2R levels in serum (p less than 0.005). These aberrant immunological phenomena were more frequent among the elderly of group A, compared to group B (p less than 0.005). In contrast to the uniform expression of various autoantibodies previously observed in group A, the autoantibody profile of group B consisted mainly of rheumatoid factor and antibodies to single-stranded DNA. Finally, no association could be demonstrated between the presence of autoantibodies and HLA antigens in 42 elderly studied.     

Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases.

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.     

Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P < 0.05). sICAM-1 levels were similar in healthy controls and in VL patients refractory to antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P < 0.05) in patients responsive to antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response.     

New concepts in chronic urticaria

Chronic urticaria is a common skin disease without a clear etiology in the vast majority of cases. The similarity of symptoms and lesion pathology to allergen-induced skin reactions supports the idea that skin mast cell and blood basophil IgE receptor activation is involved; however, no exogenous allergen trigger has been identified. The presence of serum IgG autoantibodies targeting IgE or the IgE receptor in approximately 40% of CIU cases supports the theory of an autoimmune basis for the disease. However, issues remain with the assays to detect autoantibodies among other serum factors, the relationship of autoantibodies to CIU disease activity, and the occurrence of autoantibodies in healthy subjects. Other studies have identified altered IgE receptor degranulation that reverts in disease remission and is accompanied by changes in signaling molecule expression and function in mast cells and basophils in active CIU subjects. The arrival of therapies targeting IgE and the IgE receptor pathway elements has potential use in CIU.     

Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome

BACKGROUND: Patients with mastocytosis may suffer from severe hypotension after wasp or bee stings. In these patients, no specific IgE is detectable, but they usually have skin lesions and an elevated serum tryptase level. METHODS: We report on 6 patients who were referred to our department because of severe hypotension following bee or wasp stings without cutaneous lesions. RESULTS: In 3 patients, the baseline serum tryptase level was elevated (26, 36, and 67 ng/ml, respectively), and investigation of their bone marrow revealed systemic mastocytosis (SM). In the remaining 3 patients, serum tryptase levels were <20 ng/ml, and bone marrow histology and tryptase immunohistochemistry did not reveal diagnostic mast cell infiltrates. However, in 1 patient, three minor SM criteria were demonstrable leading to the diagnosis SM, and in the 2nd patient, two minor SM criteria, including an aberrant mast cell phenotype, were found. In the 3rd patient, no minor SM criteria were detected. CONCLUSIONS: All patients with unexplained hypotension after hymenoptera stings should undergo a thorough investigation for major and minor SM criteria regardless of the tryptase level or presence of skin lesions, in order to diagnose or exclude SM or a related subdiagnostic condition (1 or 2 minor SM criteria) tentatively termed monoclonal mast cell activation syndrome.     

人巨细胞病毒感染对肾移植受者血清sIL－2R水平的影响

用ＰＣＲ检测ＨＣＭＶ－ＤＮＡ，ＥＬＩＳＡ法检测ＨＣＭＶ－ＩｇＭ及ＩｇＧ，以诊断肾移植受者ＨＣＭＶ感染。用双抗体夹心法ＥＬＩＳＡ检测６５例肾移植受者血清ｓＩＬ－２Ｒ水平，结果表明：ＨＣＭＶ感染后宿主血清ｓＩＬ－２Ｒ水平明显增高（Ｐ＜０．０１），且ＨＣＭＶ疾病组ｓＩＬ－２Ｒ增高程度大于无症状感染组（Ｐ＜０．０１）；６例原发性ＨＣＭＶ感染者ｓＩＬ－２Ｒ水平与ＩｇＭ水平呈正相关（ｒ＝０．９９０８），提示随感染程度增加，血清ｓＩＬ－２Ｒ水平随之增高，还发现血清ｓＩＬ－２Ｒ水平与Ｃ９４／ＣＤ８比值是负相关（ｒ＝－０．９７８９），说明ＨＣＭｖ感染后ｓＩＬ－２Ｒ水平增高与Ｔ细胞亚群改变有关，反之也说明ｓＩＬ－２Ｒ增高程度可表明体内免疫抑制状态。对于ＨＣＭＶ感染后血清ｓＩＬ－２Ｒ水平增高的机理有待进一步探讨。     

Identification of the Syk kinase inhibitor R112 by a human mast cell screen

BACKGROUND: Activation of the IgE receptor, FcvarepsilonRI, in mast cells is the key mechanism initiating and propagating pathophysiological responses in allergic rhinitis. OBJECTIVE: Identify and characterize a small molecule inhibitor of IgE-dependent mast cell activation for the treatment of allergic diseases. METHODS: A cell-based high-throughput screen for small molecules that block IgE signaling was performed in cultured human mast cells. A potent inhibitor, referred to as R112, was selected and characterized by using biochemical and cell-based assays. R112 effects on IgE-dependent degranulation and cytokine production was measured in mast cells and basophils and compared with other mast cell inhibitors. RESULTS: R112 inhibited degranulation induced by anti-IgE cross-linking in mast cells (tryptase release, effective concentration for 50% inhibition [EC(50)] = 353 nmol/L) or basophils (histamine release, EC(50) = 280 nmol/L), and by allergen (dust mite) in basophils (histamine release, EC(50) = 490 nmol/L). R112 also blocked leukotriene C4 production and all proinflammatory cytokines tested. Subsequent molecular characterization indicated that R112 is an ATP-competitive spleen tyrosine kinase (Syk) inhibitor (inhibitory constant [K(i)] = 96 nmol/L). Its onset of action was immediate, and the inhibition was reversible. Incubation of mast cells with R112 showed that cytokine production in mast cells was dependent on sustained activation of the FcvarepsilonRI-Lyn-spleen tyrosine kinase pathway. Unlike other mast cell inhibitors, R112 was able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production. CONCLUSION: R112 potently, completely, and rapidly abrogated all mast cell activation cascades triggered by IgE receptor cross-linking. CLINICAL IMPLICATIONS: R112 and its analogues offer a new modality in the treatment of allergic rhinitis.     

Evaluation of mast cell activation (tryptase) in two patients suffering from drug-induced hypotensoid reactions

Tryptase is predominantly found in mast cells, where it resides in secretory granules, and is released with other mediators during mast cell degranulation. By using a newly developed commercial assay for measurements of tryptase levels we have investigated two cases of suspected drug-induced anaphylaxis. Each patient had a similar clinical presentation, consisting of hypotension and cyanosis after administration of thiopentone and suxamethonium. One of the patients showed a highly elevated serum level of tryptase reaching 26 g/l 30 min after the initial reaction. In addition, slightly elevated levels of specific IgE antibodies to thiopentone were detected. The other patient with similar symptoms showed no increase in the level of tryptase, nor any specific IgE to thiopentone or suxamethonium. These data indicate the patient I suffered from true anaphylaxis, whereas the reaction of patient II occurred by a different mechanism.     

Soluble interleukin-2 receptors in plasma cell dyscrasias

Levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 69 patients with plasma cell dyscrasias. A close relationship was seen between serum sIL-2R levels and clinical features. Among patients with normal BUN and creatinine levels, the mean (+/- 1SD) level of sIL-2R in 44 patients with multiple myeloma (MM) was higher than that of normal controls (457 +/- 227 U/ml vs 288 +/- 124 U/ml, P = 0.01). The mean level of sIL-2R in eight patients with primary macroglobulinemia was 722 +/- 251 U/ml. In MM, those with active or refractory disease showed a significantly higher mean level of sIL-2R than those in the remission phase (577 +/- 240 U/ml vs 335 +/- 103 U/ml, P = 0.01). There was a negative correlation between sIL-2R and hemoglobin levels in MM patients (r = -0.45, P = 0.01). Five patients with complications of renal insufficiency had elevated levels of sIL-2R. In a longitudinal study of a patient with plasmacytoma and an extremely high sIL2-R level, the sIL-2R level showed a strong relationship with tumor burden. Patients with high sIL-2R levels generally had a poor prognosis than those with normal levels. Thus a high sIL-2R level may be an indicator of a poor prognosis in MM.     

Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

BACKGROUND: Endogenous histamine-releasing factors (HRFs) are involved in 30-60% of patients with chronic urticaria (CU). Evidence for their existence comes from in vivo studies of autoreactivity with the autologous serum skin test (ASST), in vitro immunoassays demonstrating autoantibodies against the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients. SUBJECTS: Group 1 consisted of 28 patients with CU (16 were ASST-positive) 20 patients with atopic dermatitis, 24 patients with allergy to birch and nine healthy controls. Group 2 consisted of 873 unselected CU patients. METHODS: White blood cells containing 1-2% basophils from a healthy nonatopic donor were incubated with patients sera in the presence of interleukin (IL)-3. Histamine was measured by the glass fibre method. RESULTS: Using the ASST as the true outcome, the HR-Urticaria test showed a sensitivity and specificity of 75% in group 1 using a cut-off value for HR of >16.5%. None of the controls was positive in the HR-Urticaria test. In group 2, we found no difference in the frequency of positives between male (34.6%, n = 254) and female adults (35.1%, n = 576) but twice as many females as males were tested. CONCLUSIONS: Our studies have shown that the HR-Urticaria test has a good sensitivity and specificity for endogenous HRFs demonstrated by the ASST in patients with CU and that about one-third of unselected patients with CU have a positive result.     

Rabbit F(ab')2 antihuman IgE is a universal skin test reagent in the evaluation of skin mast cell degranulation in vivo

Antihuman IgE is often used to study basophil- and mast cell-mediator release in vitro but is infrequently used in vivo. To evaluate in vivo skin reactivity to anti-IgE, an affinity-purified rabbit F(ab')2 fragment of antihuman IgE was injected intradermally in 22 nonallergic and 27 allergic subjects. All 49 subjects (including a subject with less than 1 ng/ml of total serum IgE) had positive immediate cutaneous reactions to anti-IgE. Although total serum IgE level was weakly correlated (r = -0.51; p less than 0.005) with in vivo skin reactivity to anti-IgE for the entire population, allergic subjects did not have significantly increased skin reactivity compared to nonallergic subjects (p = 0.18), despite having higher total serum IgE levels (p less than 0.002). A late-phase cutaneous response (LPR) to anti-IgE occurred in 60% of the allergic and in 50% of the nonallergic subjects. Subjects with an LPR required approximately tenfold higher concentrations of anti-IgE to produce an immediate wheal of 10 mm compared to subjects who did not develop an LPR (p = 0.02), suggesting that the concentration of the stimulus injected is more important for the development of a LPR than the size of the immediate cutaneous response. Skin reactivity to codeine phosphate (a non-IgE-dependent secretagogue) was correlated with skin reactivity to anti-IgE (r = 0.47; p less than 0.05), suggesting that in vivo skin mast cell degranulation is partially a function of mast cell releasability.(ABSTRACT TRUNCATED AT 250 WORDS)