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ABSTRACT: The role of interleukin (IL)-5 in the pathogenesis of eosinophilic esophagitis (EoE) has been established in animal models; anti-IL-5 therapy has been reported to be effective in adults. We investigated whether IL-5 has a role in accumulation of esophageal eosinophils in children with EoE and whether therapy with mepolizumab, an antibody against IL-5, reduces the number of esophageal intraepithelial eosinophils in children with EoE.
We performed an international, multicenter, double-blind, randomized, prospective study of 59 children with EoE, defined as baseline peak count of esophageal intraepithelial eosinophils of ≥ 20 in at least 1 high-power field (hpf). Patients received an infusion every 4 weeks (a total of 3 infusions) of 0.55, 2.5, or 10 mg/kg mepolizumab. No placebo group was used.
Baseline peak and mean esophageal intraepithelial eosinophil counts were (mean ± SE) 122.5 ± 8.78 and 39.1 ± 3.63 per hpf, respectively. Four weeks after the third infusion, peak eosinophil counts were <5 per hpf in 5 of 57 children (8.8%); we did not observe differences among groups given different doses of mepolizumab. Reduced peak and mean eosinophil counts, to <20 per hpf, were observed in 18 of 57 (31.6%) and 51 of 57 (89.5%) children, respectively. Peak and mean esophageal intraepithelial eosinophil counts decreased significantly to 40.2 ± 5.17 and 9.3 ± 1.25 per hpf, respectively (P < .0001). An analysis to evaluate predictors of response associated a higher mean baseline esophageal intraepithelial eosinophil count with a greater reduction in mean count (P < .0001).
IL-5 is involved in the pathogenesis of EoE in children. Mepolizumab, an antibody against IL-5, reduces esophageal eosinophilic inflammation in these patients.
Gastroenterology 08/2011; 141(5):1593-604. · 11.68 Impact Factor
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ABSTRACT: Eosinophilic esophagitis (EE) is now a commonly encountered disorder that was rarely diagnosed a decade ago.
We aimed to determine the epidemiologic and histologic features of retrospective pediatric esophageal eosinophilia before the first case of EE at our institution was recognized.
Esophageal biopsy specimens obtained between 1982 and 1999 with reflux esophagitis were re-examined and reorganized into 2 groups based on peak esophageal eosinophil number (<15 eosinophils per high-powered field [hpf] and > or =15 eosinophils/hpf). The epidemiology and histology of the entire cohort and a population-based cohort were evaluated.
Eight hundred seven biopsy specimens from 666 patients were re-examined; 198 patients had 15 eosinophils/hpf or greater. Among a population-based cohort of patients with 15 eosinophils/hpf or greater, there was a modest increase in incidence (P < .001; incidence rate ratio, 1.18; 95% CI, 1.09-1.28). After correcting for a 40-fold increase in the number of endoscopies during this time period, the proportion of biopsy specimens with 15 eosinophils/hpf or greater did not change (0.08 in 1982 vs 0.08 in 1996 [peak]; P = .9; incidence rate ratio, 1.02; 95% CI, 0.73-1.44). Patients who had as few as 5 eosinophils/hpf were more likely to have persistent esophageal eosinophilia on repeat esophagogastroduodenoscopy, evidence of basal layer hyperplasia, and lamina propria fibrosis compared with patients with less than 5 eosinophils/hpf (P < .001).
Esophageal eosinophilia at levels consistent with EE was present among 30% of patients given diagnoses of reflux esophagitis, and the incidence of esophageal eosinophilia did not change over time. Patients with 5 eosinophils/hpf or greater had evidence of other histologic abnormalities and were likely to have persistent esophageal eosinophilia.
The Journal of allergy and clinical immunology 07/2010; 126(1):112-9. · 9.17 Impact Factor
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Joseph D Sherrill,
Pei-Song Gao,
Emily M Stucke,
Carine Blanchard,
Margaret H Collins,
Phil E Putnam,
James P Franciosi,
Jonathan P Kushner,
J Pablo Abonia, Amal H Assa'ad,
Melinda Butsch Kovacic,
Jocelyn M Biagini Myers,
Bruce S Bochner,
Hua He,
Gurjit Khurana Hershey,
Lisa J Martin,
Marc E Rothenberg
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ABSTRACT: The genetic cause of eosinophilic esophagitis (EE) has been largely unexplored until a recent genome-wide association study identified a disease susceptibility locus on 5q22, a region that harbors the thymic stromal lymphopoietin (TSLP) gene. However, it is unclear whether the observed genetic associations with EE are disease-specific or confounded by the high rate of allergy in patients with EE. In addition, the genetic contributions of other allergy-associated genes to EE risk have not been explored.
We aimed to delineate single nucleotide polymorphisms (SNPs) that associated with EE apart from allergy.
We used a custom array containing 738 SNPs in 53 genes implicated in allergic responses, immune responses, or both to genotype 220 allergic or 246 nonallergic control subjects and a discovery cohort of 170 patients with EE. We replicated a statistically significant SNP association in an independent case-control cohort and examined the induction of the candidate gene in primary esophageal epithelial cells.
A single SNP residing in the TSLP gene reached Bonferroni linkage disequilibrium-adjusted significance but only when patients with EE were compared with allergic control subjects (rs10062929; P = 4.11 x 10(-5); odds ratio, 0.35). A nonsynonymous polymorphism in the thymic stromal lymphopoietin receptor (TSLPR) gene on Xp22.3 and Yp11.3 was significantly associated with disease only in male patients with EE. Primary esophageal epithelial cells expressed TSLP mRNA after Toll-like receptor 3 stimulation.
These data collectively identify TSLP as a candidate gene critically involved in EE susceptibility beyond its role in promoting T(H)2 responses.
The Journal of allergy and clinical immunology 07/2010; 126(1):160-5.e3. · 9.17 Impact Factor
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ABSTRACT: Anti-IL-5 might be a useful therapeutic agent for eosinophilic disorders, yet its immunologic consequences have not been well characterized.
We sought to characterize the hematologic and immunologic effects of anti-IL-5 in human subjects.
The effects of 3-month infusions of mepolizumab were assessed in 25 patients with a variety of eosinophilic syndromes. Samples with increased IL-5 levels after therapy were analyzed by using size exclusion filtration. Immunoreactive IL-5 fraction and plasma samples were subsequently precipitated with saturating concentrations of protein A/G.
Twenty-three patients responded to anti-IL-5 therapy with a decrease in blood eosinophil counts and a reduced percentage of CCR3(+) cells by 20- and 13-fold, respectively (P < .0001). Responsiveness was not related to the levels of baseline plasma IL-5 or the presence of FIP1L1-PDGFRA fusion gene. Persistently decreased blood eosinophilia remained for 3 months after final infusion in 76% of subjects. Therapy was associated with a large increase in blood IL-5 levels, likely because of a circulating IL-5/mepolizumab complex precipitated with protein A/G, a significant increase in eosinophil IL-5 receptor alpha expression, and increased percentage of CD4(+) and CD8(+) cells producing intracellular IL-5 (P < .05). Additionally, anti-IL-5 therapy decreased eotaxin-stimulated eosinophil shape change ex vivo.
Anti-IL-5 therapy induces a dramatic and sustained decrease in blood eosinophilia (including CCR3(+) cells), decreased eosinophil activation, and increased circulating levels of IL-5 in a variety of eosinophilic disorders. Increased levels of IL-5 receptor alpha and lymphocyte IL-5 production after anti-IL-5 therapy suggest an endogenous IL-5 autoregulatory pathway.
The Journal of allergy and clinical immunology 07/2008; 121(6):1473-83, 1483.e1-4. · 9.17 Impact Factor
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Margaret H Collins,
Carine Blanchard,
J Pablo Abonia,
Cassie Kirby,
Rachel Akers,
Ning Wang,
Philip E Putnam,
Sean C Jameson, Amal H Assa'ad,
Michael R Konikoff,
Keith F Stringer,
Marc E Rothenberg
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ABSTRACT: Eosinophilic esophagitis (EE) occurs in families.
Record review confirmed patient kinship and provided clinical information. Slide review confirmed the diagnosis (threshold peak number > or = 24 eosinophils/high-power field).
Fifty-nine members (41 males, 18 females) of 26 families were 3 months to 47 years of age (mean age, 10.3 y) at diagnosis. The only recorded race was Caucasian. In 4 families a parent of an affected male had EE. The most common complaint at diagnosis was dysphagia (68% of patients). Endoscopy showed esophageal mucosal furrows (93% of patients) and exudates (44%). Fifty-one percent had asthma. Skin prick tests to food and aeroallergens were positive in 76% and 71%, respectively. Familial EE characteristics (clinical, endoscopic, pathologic, and global esophageal transcript expression profile analysis) were similar to sporadic EE, except among patients with mucosal furrows: familial patients had lower peak eosinophil counts in the distal esophagus (P = .03) compared with sporadic patients. The basic characteristics of EE (eg, eosinophil levels, rate of atopy) did not vary with patient age. By using genome-wide microarray analysis, no significant differences (P < .05, false-discovery rate) were observed between familial and sporadic EE. Among all patients, chest pain was more common in females (P = .02), and thickened mucosa was more common in males (P = .006).
These data support a familial pattern of inheritance of EE and a pathogenesis shared with sporadic EE. EE should be considered in symptomatic family members of patients who have EE.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2008; 6(6):621-9. · 5.64 Impact Factor
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ABSTRACT: Recent genetic evidence supports that an underlying defect in skin barrier function contributes to the pathogenesis of atopic dermatitis (AD). The integrity of the skin barrier can be assessed objectively by measuring transepidermal water loss (TEWL). Previous investigations of TEWL as a biomarker of skin barrier function have been limited by small sample size, and studies including African American subjects are lacking.
We sought to determine whether children with AD have inherently altered skin barrier function by comparing TEWL as a measure of skin barrier function in African American and white children with AD with that in control subjects without AD.
TEWL was measured on nonlesional normal-appearing skin at 4 sites (the volar forearm, dorsal arm, lower leg, and cheek) in (1) children with AD (cases), (2) children with asthma or allergic rhinitis but without AD (allergic control subjects), and (3) nonatopic control subjects. AD severity was assessed by using the objective SCORAD index.
TEWL was increased in children with AD compared with that seen in both control groups at most of the anatomic sites tested (P < .05). TEWL also correlated with objective SCORAD score. The presence of allergic sensitization or other allergic conditions did not affect TEWL among children with AD. TEWL was higher in white than in African American children.
Skin barrier function as assessed by TEWL is intrinsically compromised in children with AD but not in children with other allergic conditions. The magnitude of skin barrier dysfunction correlates with AD disease severity.
The Journal of allergy and clinical immunology 03/2008; 121(3):725-730.e2. · 9.17 Impact Factor
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Jennifer Z Bullock,
Joyce M Villanueva,
Carine Blanchard,
Alexandra H Filipovich,
Philip E Putnam,
Margaret H Collins,
Kimberly A Risma,
Rachel M Akers,
Cassie L Kirby,
Bridget K Buckmeier, Amal H Assa'ad,
Simon P Hogan,
Marc E Rothenberg
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ABSTRACT: Pediatric eosinophilic esophagitis (EE) is a recently described disorder associated with atopy. Although studies of esophageal tissue suggest that Th2 cytokines and eotaxin-3 may be crucial in disease pathogenesis, little is known about the systemic immunological phenotypes of children with EE.
To define the phenotypes of peripheral blood eosinophils and lymphocytes in EE and to examine for correlations between these parameters and tissue eosinophil numbers and disease severity.
Blood was collected from children with EE, atopic control children without EE, and nonatopic control children without EE. Flow cytometry was used to measure eosinophil expression of chemokine receptor 3 (CCR3) and interleukin-5 receptor-alpha (IL-5Ralpha), and intracellular lymphocyte expression of IL-4, IL-5, IL-13, interferon-gamma, and tumor necrosis factor-alpha. Eosinophil numbers and eotaxin-3 mRNA levels were quantitated in esophageal biopsy specimens.
Compared with nonatopic control children, EE patients with active disease had increased peripheral blood eosinophil percentages, mean channel of fluorescence (MCF) of CCR3 on eosinophils, and percentage of CD4+ T cells expressing IL-5. Notably, these parameters positively correlated with esophageal eosinophil numbers. Eotaxin-3 tissue expression positively correlated with esophageal eosinophil numbers and peripheral blood eosinophil CCR3 MCF. The percentage of peripheral blood eosinophils, eosinophil CCR3 MCF, and CD4+ T cell expression of IL-5 were lower in EE patients in disease remission than in patients with active disease.
Collectively, these studies demonstrate cooperation between systemic CD4+ Th2-cell-mediated immunity and an enhanced eosinophil-CCR3/eotaxin-3 pathway in EE pathogenesis. Furthermore, the imbalanced Th2 immunity and increased CCR3 expression are reversible with disease remission.
Journal of pediatric gastroenterology and nutrition 08/2007; 45(1):22-31. · 2.18 Impact Factor
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Amal H Assa'ad,
Philip E Putnam,
Margaret H Collins,
Rachel M Akers,
Sean C Jameson,
Cassie L Kirby,
Bridget K Buckmeier,
Jennifer Z Bullock,
Ann R Collier,
Michael R Konikoff,
Richard J Noel,
Jesus R Guajardo,
Marc E Rothenberg
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ABSTRACT: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients.
We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history.
We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years.
In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed.
Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus.
Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.
Journal of Allergy and Clinical Immunology 04/2007; 119(3):731-8. · 11.00 Impact Factor
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Michael R Konikoff,
Richard J Noel,
Carine Blanchard,
Cassie Kirby,
Sean C Jameson,
Bridget K Buckmeier,
Rachel Akers,
Mitchell B Cohen,
Margaret H Collins, Amal H Assa'ad,
Seema S Aceves,
Philip E Putnam,
Marc E Rothenberg
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ABSTRACT: Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis.
We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 mug of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of </=1 eosinophil in all 400x fields in both the proximal and distal esophagus.
Fifty percent of FP-treated patients achieved histologic remission compared with 9% of patients receiving placebo (P = .047). FP decreased esophageal eosinophil levels, with a more pronounced effect in nonallergic individuals (65.9 +/- 25.3 vs 1.4 +/- 1.1 eosinophils/high-power field in the proximal esophagus [P = .03] and 84.6 +/- 19.7 vs 19.6 +/- 12.9 eosinophils/high-power field in the distal esophagus [P = .04]). Resolution of vomiting occurred more frequently with FP than placebo (67% vs 27%; P = .04). FP-induced resolution of mucosal eosinophilia was associated with resolution of endoscopic findings, epithelial hyperplasia, younger age (P = .0003), shorter height (P = .002), and lighter weight (P = .02). Effective treatment with FP decreased the number of CD8(+) T lymphocytes and mast cells in both the proximal and distal esophagus (P < .05).
Swallowed FP is effective in inducing histologic remission in eosinophilic esophagitis, with a more pronounced effect in nonallergic and younger individuals, especially in the proximal esophagus.
Gastroenterology 12/2006; 131(5):1381-91. · 11.68 Impact Factor
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ABSTRACT: Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment.
We hypothesized that the humanized monoclonal IgG(1) antibody against human IL-5 (mepolizumab) may be useful in the control of EE.
An open-label phase I/II safety and efficacy study of anti-IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti-IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3+ cells in blood, quality of life measurements, and histological analysis of esophageal biopsies were determined before and 1 month after treatment.
Peripheral blood eosinophilia and percent of CCR3+ cells decreased by 6.4-fold and 7.9-fold (P < .05), respectively, after anti-IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (x400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life (P = .03). Therapy was generally well tolerated, and responsiveness to anti-IL-5 therapy did not correlate with plasma IL-5 levels.
Anti-IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3+ blood cells) in patients with EE and improved clinical outcomes.
Anti-IL-5 is a promising therapeutic intervention for EE.
Journal of Allergy and Clinical Immunology 12/2006; 118(6):1312-9. · 11.00 Impact Factor
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Amal H Assa'ad
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ABSTRACT: GI symptoms are a common manifestation of food allergy and intolerance. The primary physician is the first to evaluate these symptoms. A systematic evaluation using an accurate and detailed history, tests to identify the offending food(s), and procedures that may identify underlying pathologic disorders of the GI tract would lead to an accurate diagnosis and better targeted therapeutic interventions.
Pediatric Annals 11/2006; 35(10):718-26. · 0.48 Impact Factor
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Carine Blanchard,
Ning Wang,
Keith F Stringer,
Anil Mishra,
Patricia C Fulkerson,
J Pablo Abonia,
Sean C Jameson,
Cassie Kirby,
Michael R Konikoff,
Margaret H Collins,
Mitchell B Cohen,
Rachel Akers,
Simon P Hogan, Amal H Assa'ad,
Philip E Putnam,
Bruce J Aronow,
Marc E Rothenberg
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ABSTRACT: Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.
Journal of Clinical Investigation 03/2006; 116(2):536-47. · 15.39 Impact Factor
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ABSTRACT: Hypereosinophilic syndromes represent a heterogeneous group of disorders characterized by peripheral eosinophilia and end-organ damage associated with eosinophil infiltrations. In many instances, the eosinophilia is refractory to standard therapies and clinicians rely on potentially toxic alternatives. This group of disorders has recently gained attention with the description of patients that harbor a genetic rearrangement that produces a constitutively active tyrosine kinase, often responsive to anti-tyrosine kinase therapy. In addition, the recent expansion in our understanding of the mechanisms by which eosinophils develop and become activated, involving the cytokine interleukin-5 (IL-5), has led to advances in therapeutic options. A new therapy currently in clinical trials is the humanized monoclonal antibody against IL-5. This review will discuss the etiology, classification, and treatment options for the hypereosinophilic syndromes, with particular emphasis on anti-interleukin-5 therapy.
Clinical Immunology 05/2005; 115(1):51-60. · 4.05 Impact Factor
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ABSTRACT: Eosinophilic esophagitis (EE) is a recently recognized clinical disorder that is understood poorly. We aimed to determine the efficacy of swallowed fluticasone propionate on the immunopathologic features associated with EE.
A retrospective analysis was performed on 20 pediatric patients with EE. Inclusion criteria specified a peak eosinophil density of > or =24 cells per 400x field in the esophagus and treatment with swallowed fluticasone between 2 endoscopic assessments. Histologic specimens were examined for eosinophil and CD8(+) lymphocyte infiltration, papillary lengthening, and proliferation of the basal layer as determined by monoclonal anti-Ki-67 (MIB-1) antibody staining.
The mean time interval between endoscopic assessments was 4.8 months. The patients were divided equally between allergic and nonallergic groups based on the results of skin-prick testing. All of the nonallergic patients responded to fluticasone propionate. The endoscopic appearance of the mucosa improved and microscopic evaluation showed markedly reduced eosinophil infiltration, reduced basal layer hyperplasia documented by a reduced number of MIB-1(+) cells, and a reduced number of CD8(+) lymphocytes. However, allergic patients were relatively refractory to therapy; 20% had a partial response, whereas 20% had no detectable improvement. Esophageal eosinophil levels before and after therapy in all patients strongly correlated with the level of epithelial cell proliferation as measured by MIB-1 staining.
Collectively, these results suggest that patients treated with swallowed fluticasone have improved endoscopic, histologic, and immunologic parameters associated with EE. However, patients with identifiable allergies who fail dietary elimination may have a blunted response to treatment.
Clinical Gastroenterology and Hepatology 07/2004; 2(7):568-75. · 5.63 Impact Factor
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Jennifer K Garrett,
Sean C Jameson,
Blythe Thomson,
Margaret H Collins,
Lynne E Wagoner,
Debbie K Freese,
Lisa A Beck,
Joshua A Boyce,
Alexandra H Filipovich,
Joyce M Villanueva,
Steven A Sutton, Amal H Assa'ad,
Marc E Rothenberg
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ABSTRACT: IL-5 is a cytokine critically involved in regulating several aspects of eosinophils including their production, activation, and tissue recruitment. As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia.
We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hyper-eosinophilic syndromes.
We performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10 mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with hypereosinophilic syndromes (defined by peripheral blood and/or tissue eosinophilia). The effects of treatment on safety, eosinophil levels (in peripheral blood and/or diseased tissue), pulmonary function, and quality of life were measured over a 28-week period.
Anti-IL-5 was well tolerated in all patients and lowered peripheral blood eosinophil counts despite ongoing systemic glucocorticoid therapy. The decline in circulating eosinophil counts was sustained for at least 12 weeks after the last dose of anti-IL-5. In addition, anti-IL-5 improved clinical and quality of life measurements. In one patient with striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a 10-fold reduction in tissue eosinophil levels.
These results suggest that anti-IL-5 is safe, effective in lowering eosinophil levels, and has potential glucocorticoid-sparing effects in patients with a variety of hyper-eosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic potential for hypereosinophilic syndromes.
Journal of Allergy and Clinical Immunology 02/2004; 113(1):115-9. · 11.00 Impact Factor
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Journal of Allergy and Clinical Immunology 12/2003; 112(5):1011-2. · 11.00 Impact Factor
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Journal of Allergy and Clinical Immunology 06/2002; 109(5):888-9. · 11.00 Impact Factor
