On the Lipophilic Nature of Autoreactive IgE in Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is a skin disease related to autoreactive IgE in at least a subgroup of patients. However, the nature of this autoreactive IgE remains poorly characterized. This investigation had three objectives: first, to quantity CSU autoreactive IgE; second, to recognize the patterns of CSU autoreactive IgE compared with healthy control IgE; and third, to investigate the physiochemical nature of CSU autoreactive IgE. Methods: IgE autoreactivity was assessed in sera from 7 CSU and 7 healthy individuals. Autoantigen recognition patterns were assessed using principal component analysis (PCA) and heatmap visualization. Lipophilicity was assessed using NanoOrange reagent. Results: First, although total IgE levels did not differ significantly, the autoreactive proportion of IgE of CSU patients was 62% +/- 37%, 1000-fold higher than that of healthy controls 0.03% +/- 0.008% (P = 0.0006). Second, CSU autoreactive IgE differed from healthy control IgE by recognizing more and different autoantigens (226 vs. 34; P = 0.01). Third, the median (with 10-90% percentiles) serum level of lipophilic IgE was 39% (38-40%) in 232 CSU patients, 1.4-fold higher than the 28% (26-29%) of 173 healthy controls (P < 0.0001). Furthermore, lipophilicity correlated with autoreactivity (r = 0.8; P < 0.0001), connecting these two observed features. Conclusion: We believe that these novel observations about CSU autoreactive IgE, particularly the finding that it is more lipophilic than that of IgE from healthy individuals, will lead to the development of new diagnostic tests and therapies for autoreactive IgE-mediated diseases

Predictors of treatment response in chronic spontaneous urticaria

The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second-generation H-1-antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described. Here, we discuss the most promising predictors of response and nonresponse to these treatments in CSU. A systematic search was performed by two independent researchers using the MEDLINE/PubMed database with specific keywords and 73 studies included in the review. Levels of evidence were categorized as strong (robust predictors), weak (emerging predictors) or no association, based on the outcome and number of studies available. High disease activity, high levels of C-reactive protein and D-dimer are robust predictors for a poor or no response to sgAHs. Poor or no response to omalizumab is robustly predicted by low serum levels of total IgE. A good response to cyclosporine is robustly predicted by a positive basophil histamine release assay, whereas low total IgE is an emerging predictor. The response to treatment with sgAHs, omalizumab and cyclosporine can be predicted by the use of markers that are readily available in routine clinical practice. Further studies are needed to confirm these predictors

Bilastine: a lifetime companion for the treatment of allergies.

AbstractObjective: Bilastine is a potent and highly selective H1-antihistamine approved for the treatment of allergic rhinoconjunctivitis and urticaria. This article summarizes available data on th..

IgM and IgA in addition to IgG autoantibodies against FcɛRIα are frequent and associated with disease markers of chronic spontaneous urticaria

Background IgG autoantibodies against the high-affinity IgE receptor, FcɛRIα, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known whether such patients also exhibit IgM or IgA autoantibodies against FcɛRIα. To address this question we developed an ELISA to assess serum levels of IgG, IgM, and IgA autoantibodies against FcɛRIα and investigated whether their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST). Methods Serum samples of 35 CSU patients (25 ASST-positive) and 52 healthy control individuals were analyzed using a newly developed competitive ELISA for IgG, IgM, and IgA autoantibodies to FcɛRIα. Results One in four CSU patients (8/35, 24%) had elevated serum levels of IgG-anti-FcɛRIα compared with (3/52, 6%) healthy controls. More than half of patients had IgM (21/35, 60%) and IgA (20/35, 57%) vs (3/52, 5%) each in healthy controls. Elevated IgM, but not IgG or IgA, autoantibodies were significantly more frequent in ASST-positive CSU patients (18/25, 72%) compared with ASSTnegative patients (3/10, 33%,P = .022). Also, elevated levels of IgM-anti-FcɛRIα, but not of IgG or IgA against FcɛRIα, were linked to low blood basophil (r = .414,P = .021) and eosinophil (r = .623,P < .001) counts. Conclusions Increased serum levels of IgM-anti-FcɛRIα are common in patients with CSU and linked to features of autoimmune CSU. The role and relevance of autoantibodies to FcɛRIα in CSU can and should be further characterized in future studies, and our novel assay can help with this

Urticaria in Pregnancy and Lactation

Chronic urticaria (CU) is a mast cell-driven chronic inflammatory disease with a female predominance. Since CU affects mostly females in reproductive age, pregnancy is an important aspect to consider in the context of this disease. Sex hormones affect mast cell (MC) biology, and the hormonal changes that come with pregnancy can modulate the course of chronic inflammatory conditions, and they often do. Also, pregnancy-associated changes in the immune system, including local adaptation of innate and adaptive immune responses and skewing of adaptive immunity toward a Th2/Treg profile have been linked to changes in the course of inflammatory diseases. As of now, little is known about the effects of pregnancy on CU and the outcomes of pregnancy in CU patients. Also, there are no real-life studies to show the safety of urticaria medications during pregnancy. The recent PREG-CU study provided the first insights on this and showed that CU improves during pregnancy in half of the patients, whereas it worsens in one-third; and two of five CU patients experience flare-ups of their CU during pregnancy. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends adopting the samemanagement strategy in pregnant and lactating CU patients; starting treatment with standard doses of second-generation (non-sedative) H1 antihistamines, to increase the dose up to 4-folds in case of no response, and to add omalizumab in antihistamine-refractory patients; but also emphasizes the lack of evidence-based information on the safety and efficacy of urticaria treatments during pregnancy. The PREG-CU study assessed treatments and their outcomes during pregnancy. Here, we review the reported effects of sex hormones and pregnancy-specific immunological changes on urticaria, we discuss the impact of pregnancy on urticaria, and we provide information and guidance on the management of urticaria during pregnancy and lactation

Relationship between body mass index and length of hospital stay for gallbladder disease.

Background: Obesity increases the risk of hospital admission for gallbladder disease but its impact on the length of hospital stay is largely unknown. Methods: Prospective population-based study of 1.3 million women aged 56 years on average, recruited from 1996 to 2001 in England and Scotland and followed-up through NHS hospital admission record databases for gallbladder disease (cholelithiasis, cholecystitis, cholecystectomy) over a total of 7.8 million person-years. Results: During follow-up, 24 953 women were admitted with gallbladder disease, 87% who had a cholecystectomy. After adjusting for age, socioeconomic status and other factors, women with higher BMI at recruitment to the study were more likely to be admitted and spend more days in hospital. For 1000 person-years of follow-up, women in BMI categories of 18.5-24.9, 25-29.9, 30-39.9, 40+ kg/m2 spent, respectively, 16.5[16.0-17.0], 28.6[28.3-28.8], 44.0[43.4-44.5] and 49.4[45.7-53.0] days in hospital for gallbladder disease. Conclusion: On the basis of these estimates, over a quarter of all the days in hospital for gallbladder disease in middle-aged women can be attributed to obesity

The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

[1] The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from ∼6% in Version 2.0 to ∼11% in Version 3.0

Evidence for histamine release in chronic inducible urticaria – A systematic review

BackgroundChronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU.MethodsWe systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or in vitro or ex vivo histamine release (indirect evidence) following trigger exposure.ResultsAn initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H1-antihistamines.ConclusionsHistamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU