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The World Allergy Organization Journal logoLink to The World Allergy Organization Journal
. 2023 Jan 31;16(2):100742. doi: 10.1016/j.waojou.2023.100742

Immunoglobulin E and G autoantibodies against eosinophil proteins in children and adults with asthma and healthy subjects

Jorge Sánchez a,∗, Andres Sánchez Biol a,b, Marlon Múnera Biol b, Elizabeth García c, Juan-Felipe López a
PMCID: PMC10024149  PMID: 36941898

Abstract

Background

Autoimmune IgG response has been described in the pathogenesis of asthma in adults, but IgE autoimmunity has been little explored. Considering high levels of blood eosinophils and immunoglobulin E in asthmatic patients, the possibility of IgE autoantibody response to eosinophil proteins arises.

Objective

To explore the presence of IgE and IgG autoantibodies against Eosinophil peroxidase (EPX) and Eosinophil cationic protein (ECP).

Methods

Three steps were followed: 1) The frequency of IgE and IgG autoantibodies against EPX and ECP was investigated among asthmatic and healthy subjects. 2) The ability of IgE autoantibodies to induce an inflammatory response (basophil activation) was performed. 3) The capacity of autoantibodies to identify patients with severe asthma was evaluated.

Results

Asthmatic and healthy subjects had IgE and IgG autoantibodies against EPX and ECP. Anti-EPX IgE was significantly higher in asthmatic patients. Severe asthmatic patients had a higher frequency and higher levels of IgE and IgG autoantibodies compared to healthy subjects. There was not a correlation between autoantibodies and blood eosinophils. Children younger than 14 years of age had IgE and IgG autoantibodies against to EPX and ECP. IgE autoantibodies to EPX and ECP induced basophil activation in asthmatic patients.

Conclusion

In this study, we identify for the first time IgE autoantibodies against EPX and ECP in adults and children patients with asthma; IgE and IgG autoantibodies against EPX and ECP could serve as a predictive biomarker of the clinical severity.

Keywords: Asthma, Autoreactivity, Autoantibodies, Eosinophils, Immunoglobulin E

Introduction

Allergic asthma is a common respiratory disease with a high impact on quality of life.1 The clinical definition of asthma covers different phenotypes and endotypes that are strongly related to age. Based on the characteristics of the inflammatory process, Th2 cytokines are the most prevalent in patients with asthma (60%–80%),2,3 especially in childhood. In this type of inflammation, specific IgE against environmental allergens and recruitment of eosinophils are important mediators of lung symptoms.4,5 In recent years, new mechanisms have been proposed; IgG reactivity to several autoantigens has been reported in adult patients with asthma,6,7 opening the hypothesis of an autoimmune endotype. IgE autoreactivity against autoantigens and its role in inflammation has been demonstrated in different diseases8, 9, 10, 11, 12 but little is known about asthma and its presence in childhood population.

Mediators of the inflammatory asthma process include basophils, neutrophils, and especially eosinophils.13,14 Eosinophils through their proteins such as major basic protein (MBP), eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP) are capable of generating an inflammatory response.15,16 Recently, sputum IgG response against EPX was detected in asthma and it was associated with severe asthma and corticosteroids resistance.6

Considering the central role of specific IgE and eosinophil cytoplasmic granules in the pathogenesis of asthma, we hypothesized that EPX and ECP may be possibly recognized by IgE autoantibody, and this response could be associated with chronicity and severity of the disease. The aim of this study was to investigate the presence of IgE and IgG autoantibodies against eosinophil proteins EPX and ECP and to explore the possible relationship with asthma inflammation and age.

Methods

Study design and population

A cross-sectional study was performed using 2 groups: asthmatic and healthy subjects. The asthma group included patients with at least 2 years of asthma recruited from 3 medical institutions in Medellín, Colombia. Control subjects were students and workers invited from educational institutions. Severity of asthma was defined according to GINA 2020 recommendations by treatment (https://ginasthma.org/); Mild asthma corresponds to a disease that can be controlled with step 1 or 2 treatment, moderate asthma was step 3 or 4 and severe asthma was step 5 treatment. Patients with clinical indication for the use of a biological therapy for asthma were included if they had not started such therapy. Subjects in both groups consisted of people between 5 and 55 years without a clinical history of autoimmune diseases, atopic dermatitis, chronic obstructive pulmonary disease, or any other chronic pulmonary disease. Smokers were excluded in both groups.

Participants with a diagnosis of systemic diseases (eg, mastocytosis, dermatitis), infection within 4 weeks of participation, or pharmacologic treatment (eg, Cyclosporine), that could affect the interpretation of the laboratory results were not included.

Antigen's production

ECP and EPX were obtained as recombinant proteins according to a previous protocol10,17 using Escherichia coli BL21 (DE3) as an expression vector.

Determination of the total IgE, specific IgE and IgG autoantibodies

Total IgE levels in the serum samples were determined using a fluoroenzyme immunoassay (ImmunoCap System, Thermofisher, Sweden). When the levels were above the reading range of the equipment (>100 KUA/mL), the sample was diluted 1:5 or 1:10 depending on the case, and the total concentration was calculated by conversion.

We explored the presence of IgE autoantibodies against EPX, and ECP by ELISA technique after purification to avoid contamination of vector proteins.10,17 The sera used for the quantification of IgE were previously depleted of IgG by immunoaffinity depletion; For each 500 L of serum and 1X PBS (1:5) were added 80 L of Protein G (Sigma-P3296, Protein G Sepharose®). After 60 min of incubation at room temperature (RT) on a rotating platform, the serum was recovered by centrifugation and stored at −20 °C until use. Residual IgG contents in protein G-adsorbed sera were measured by enzyme-linked immunosorbent assay (ELISA) assays and sera were accepted for anti-EPX/ECP IgE measure when IgG were found to be less than 10 μg/mL. The specificity of the binding was evaluated by inhibition tests.

For ELISA, 100 μL was loaded into wells by duplicated coated with the relevant antigen, and the plates were incubated overnight. Each plate had control and asthma samples. A calibration curve was done (0.001, 0.01, 0.1, 1 u/ml) for each antigen and PBS as negative controls was used. Considering previous studies,18,19 antigens were reduced with SDS. The cut-off value for serum anti-EPX IgE and anti-ECP IgE were defined as the mean plus three standard deviations of absorbance values from 60 healthy controls (IgE-EPX 0.354, IgE-ECP 0.279, IgG-EPX 0.425, IgG-ECP 0.414). The results were expressed in optical density units (OD). The absorbance at 405 nm was determined using a spectrophotometer.

For the determination of anti-TPO IgG, the same protocol was followed, except for the IgG depletion and that the human sera adsorbed with E. coli lysate were diluted 1:50 and the secondary antibody was alkaline phosphatase-conjugated anti-IgG (Pharmigen).

CD203c expression

Peripheral blood basophils were obtained from subjects from each group. We used the CD203c expression protocol previously reported.10,17 Briefly, basophil activation test (BAT) was performed with the whole blood collected in EDTA tubes and red blood cells were lysed with a lysis buffer. The 100 μL of the leukocyte suspension were added along with calcium ionophore, anti-human goat IgE antibodies and anti-IgG4. Basophil activation was stimulated with different concentrations of EPX/ECP antigens (0.01, 0.1 and 1 μg/mL). After washing with PBS, the cells were stained with phycoerythrin (PE)-conjugated antihuman CD203c and fluorescein isothiocyanate (FITC)-conjugated antihuman CD123. CD203c expression was measured by flow cytometry.

The percentage of CD203c expression was defined as the percentage of basophils expressing more CD203c than the critical point, which was ≥10.0% of the basophils incubated with buffer only, similar to previous studies.10,17,20

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 21.0 (IBM, Inc, Chicago, IL) and GraphPad Prism 8 (La Jolla, CA). The Shapiro–Wilk test was used to check for normality, and our descriptive and statistical analyses were chosen according to the results. The data are presented as the means and standard deviation for variables with a normal distribution and as the median and range when not. The Mann–Whitney U test were used to compare specific IgE levels. Fisher's χ2 test was used to evaluate the differences among groups and proportions. Correlations were assessed with the Pearson or Spearman coefficient (r).

Given the results of previous studies,21, 22, 23, 24 we considered that a sample of at least 30 patients with asthma and 40 healthy subjects would be adequate to ensure a power of 80% and an alpha error of 0.05 for the primary outcome (the presence of IgE autoantibodies).

Results

Patients’ characteristics

Sixty control subjects and 55 asthmatic patients were recruited (Table 1). More sociodemographic characteristics were similar in both groups. The asthmatic group had higher levels of total IgE (mean 181 vs 139 IU/mL) and blood eosinophils (mean 126 vs 106 cells/ml) but these 2 variables were not significantly different. Atopy was present in 70.9% of the asthmatic patients and 20% of control subjects (p < 0.001). Nasal diseases (rhinitis, rhinosinusitis, polyposis), positive anti-nuclear antibodies, and family history of autoimmunity comorbidities were more frequent in asthmatic group, but only rhinitis was significant (p < 0.001).

Table 1.

Sociodemographic characteristics.

General characteristics Asthma (n = 55) Control (n = 60) P value
Age Median, (Range, min-max) 206, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,44, 44, 45, 46, 47, 48, 49, 50 236, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,44, 44, 45, 46, 47, 48, 49, 50 0.3
Age ≤ 14 years (%) 17 (30.9%) 15 (25%) 0.3
Sex: male, n (%) 30 (54.5%) 26 (43.3%) 0.2
Atopy (%) 39 (70.9%) 12 (20%) <0.001
Rhinitis (%) 43 (78.2%) 11 (18.3%) <0.001
Sinusitis (%) 6 (10.9%) 2 (3.3%) 0.1
CRS with polyps (%) 2 (3.6%) 0 0.2
ANAs (%) 4 (7,2%) 1 (1.6%) 0.1
Family history of autoimmunity 8 (14,4%) 4 (6.6%) 0.2
Total IgE (IU/ml), mean ± SD 181 (174) 139 (84) 0.1
Eosinophil serum (cells/ml) mean ± SD 126 (71) 10744 0.08
Asthma severity according GINA stepsModerateSevere 42 (76.3%)
13 (23.6%)		 N/A
N/A		 N/A
N/A
Patients with OCS in the last year 11 (20%) N/A N/A
Years with Asthma median, (Range) 38 N/A N/A
FEV1 (%) median, (Range) 8930 N/A N/A
FEV1/FVC ratio median, (Range) 0,80 (0.5) N/A N/A
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All subjects were over 6 years old. N/A: Not applicable. SD: Standard deviation. FVC: Forced vital capacity, FEV1: Forced expiratory volume. Atopy was defined as the presence of specific IgE to an allergenic source (mites, pets, etc.). The patients in the control group were not evaluated for lung function because they did not have respiratory symptoms

IgE against eosinophil autoantigens

Anti-EPX IgE and anti-ECP IgE levels were significantly higher in the asthma group versus control group (Fig. 1). Eight asthmatic patients have anti-EPX IgE and 5 have anti-ECP IgE above the detection threshold (Fig. 1); Three of these patients have both anti-ECP IgE and anti-EPX IgE. Despite the higher number of positive anti-ECP/EPX IgE in the asthma group, only anti-EPX IgE was statistically significant in the asthma group versus control group (anti-ECP IgE 0.04). Patients with IgE autoantibodies against EPX or ECP have a lower FEV1 than asthmatic patients without IgE autoantibodies (91.1% vs 78.3%, p = 0.02) and lower FEV1/FVC (0.82 vs 0.74, p = 0.03).

Fig. 1.

Fig. 1

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Asthma IgE and IgG against EPX and ECP. In a, patients with IgE or IgG autoantibodies are presented in circles and were compared between groups. In b, concentration levels according to optical density units and eosinophil blood count are presented in mean and standard deviation and were compared between groups. Cut-off; IgE-EPX 0.354, IgE-ECP 0.279, IgG-EPX 0.425, IgG-ECP 0.414

The age minimum and maximum (min-max) of the subjects with IgE autoantibodies was 6–33 years; in the asthma group; most of them had severe asthma (n = 6) (Table 2). Nine asthmatic and 3 subjects in the control groups had IgE autoantibodies and IgG autoantibodies.

Table 2.

Subjects with IgE autoantibodies.

Group Age Sex Atopy Rhinosinusitis Severity OSC FEV1 FEV1/FVC Blood eosinophils (cell/mL) Total IgE (IU/mL) Anti-EPX IgE Anti-ECP IgE Anti-EPX IgG Anti-ECP IgG
Asthma 16 Female Yes No Severe 2 77 0.67 132 122 Yes Yes Yes Yes
Asthma 25 Female Yes Yes Moderate 0 80 0.81 221 300 Yes Yes Yes Yes
Asthma 12 Male Yes Yes Severe 1 95 0.89 140 50 Yes No Yes No
Asthma 6 Female Yes No Severe 2 55 0.6 92 223 Yes No No No
Asthma 17 Male No No Severe 2 70 0.61 128 111 Yes Yes Yes No
Asthma 28 Female Yes Yes Severe 1 75 0.7 314 1042 Yes No Yes No
Asthma 17 Male No No Severe 1 80 0.9 57 55 Yes No Yes Yes
Asthma 24 Male Yes Yes Moderate 0 98 0.85 315 888 Yes No Yes Yes
Asthma 7 Female Yes No Severe 2 77 0.7 205 333 No Yes No Yes
Asthma 33 Male Yes No Moderate 0 93 0.86 100 128 No Yes No Yes
Control 10 Male Yes No N/A N/A N/A N/A 122 169 Yes No Yes No
Control 30 Female No No N/A N/A N/A N/A 130 148 Yes No Yes No
Control 20 Female No No N/A N/A N/A N/A 140 175 No Yes No Yes
Control 11 Female No Yes N/A N/A N/A N/A 199 201 No Yes No No
Control 23 Female No No N/A N/A N/A N/A 134 123 No Yes No No
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Asthma patients in control subjects with anti-EPX IgE or anti-ECP IgE. FVC: Forced vital capacity, FEV1: Forced expiratory volume. N/A: No apply. OCS: Cycles of oral systemic corticosteroid

Asthma and control group showed a low but significant correlation among the total IgE levels and number of eosinophils in serum (Asthma group r = 0.480, CI 0.232 to 0.662, p = 0.002. Control group r = 0.360, CI = 0.109 to 0.568, p = 0.005) (Fig. 3). There was not an association between autoantibody levels and blood eosinophils according to correlation or using different cut-off stratification (>150 cells/ml or >300 cells/ml eosinophils).

Fig. 3.

Fig. 3

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Basophil activation test with EPX and ECP. Basophil activation test using different concentrations of EPX and ECP. EPX: Eosinophil peroxidase. ECP: Eosinophil cationic protein. In the table CD203c activation is presented in median and range. “n” number of patients per group. For Control (+) anti-EPX IgE we put the value of CD203 expression for each patient

IgG against eosinophil autoantigens

In the asthma and control group, anti-EPX IgG was the most prevalent autoantibody, the asthma group had a higher frequency of IgG autoantibodies than the control group (18 (32.7%) vs 10 (16.6%) p = 0.04) (Table 3). The age minimum and maximum of the subjects with IgG antibodies was 7–50 years; 7 of them had severe asthma (n = 7) (Table 3).

Table 3.

Subjects with IgG autoantibodies.

Group Age Sex Atopy Rhinosinusitis Severity OCS FEV1 FEV1/FVC Blood eosinophils (cell/mL) Total IgE Anti-EPX IgE Anti-ECP IgE Anti-EPX IgG Anti-ECP IgG
Asthma 16 Female Yes No Severe 2 77,3 0,67 132 122 Yes Yes Yes Yes
Asthma 25 Female Yes Yes Moderate 0 80 0,81 221 300 Yes Yes Yes Yes
Asthma 17 Male No No Severe 2 70 0,61 128 111 Yes Yes Yes No
Asthma 28 Female Yes Yes Severe 1 75 0,7 314 1042 Yes No Yes No
Asthma 17 Male No No Severe 1 80 0,9 57 55 Yes No Yes Yes
Asthma 24 Male Yes Yes Moderate 0 98 0,85 315 888 Yes No Yes Yes
Asthma 7 Female Yes No Severe 2 77 0,7 205 333 No Yes No Yes
Asthma 33 Male Yes No Moderate 0 93 0,86 100 128 No Yes No Yes
Asthma 12 Male Yes Yes Severe 1 95 0,89 140 50 No No Yes No
Asthma 18 Female Yes No Moderate 0 102 0,78 156 156 No No Yes No
Asthma 13 Male Yes No Moderate 0 97 0,85 125 101 No No Yes No
Asthma 14 Male Yes No Moderate 0 89 0,85 126 101 No No Yes No
Asthma 20 Female Yes No Moderate 0 96 0,9 130 222 No No Yes No
Asthma 35 Male No No Moderate 0 93 0,71 135 132 No No Yes No
Asthma 40 Male Yes No Moderate 0 95 0,95 126 20 No No Yes No
Asthma 50 Female Yes No Severe 3 55 0,59 130 115 No No Yes Yes
Asthma 45 Female Yes No Moderate 0 101 0,8 120 113 No No No Yes
Asthma 29 Female No No Moderate 0 96 0,83 90 133 No No No Yes
Control 10 Male Yes No N/A N/A N/A N/A 122 169 Yes No Yes No
Control 30 Female No No N/A N/A N/A N/A 130 148 Yes No Yes No
Control 20 Female No No N/A N/A N/A N/A 140 175 No Yes No Yes
Control 24 Male No No N/A N/A N/A N/A 55 110 No No Yes No
Control 33 Female No No N/A N/A N/A N/A 110 101 No No Yes No
Control 41 Male No No N/A N/A N/A N/A 121 88 No No Yes No
Control 46 Male No No N/A N/A N/A N/A 66 53 No No Yes No
Control 30 Female No No N/A N/A N/A N/A 160 113 No No Yes Yes
Control 33 Male No No N/A N/A N/A N/A 130 145 No No No Yes
Control 34 Female No No N/A N/A N/A N/A 109 115 No No No Yes
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Asthma patients in control subjects with anti-EPX IgG or anti-ECP IgG. FVC: Forced vital capacity, FEV1: Forced expiratory volume. N/A: No apply. OCS: Cycles of oral systemic corticosteroid

Asthmatic patients exhibited significantly higher levels of IgG autoantibodies than control subjects (Fig. 1). There was no correlation among autoantibodies levels (Fig. 2).

Fig. 2.

Fig. 2

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Correlations among autoantibodies and eosinophil count. Concentration of IgE and IgG autoantibodies are presented according OD level. ECP: Eosinophil cationic protein. EPX: Eosinophil peroxidase

Patients with IgG autoantibodies against EPX or ECP have a lower FEV1 than asthmatic patients without IgG autoantibodies (91.1% vs 87.1%, p = 0.06) and lower FEV1/FVV (0.82 vs 0.79, p = 0.1) but it was not significant.

Basophil activation test (BAT)

We observed a similar concentration of basophils in total blood in the 2 groups, being slightly lower in the asthmatic group (28 cells/ul) compared to the control group (40 cells/ul), but without statistical differences.

For the BAT, basophils were obtained from different groups of subjects according to the presence (or not) of asthma, IgE, and IgG autoantibodies (Fig. 3). With the different dilutions of autoantigens used, CD203c expression from patients with asthma and IgE autoantibodies significantly increased in contrast to the other groups.

Basophils of control subjects with IgE autoantibodies have a CD203c expression over 10% when stimulated with the higher concentration of EPX or ECP (1 μg/mL), but it was significantly lower than the asthma group and without significant difference with control subjects with negative IgE autoantibodies (Fig. 3). When analyzing all samples as a group, we observed a moderate correlation between basophil activation and the concentration of anti-EPX IgE (r 0.689 p 0.03) and anti-ECP (r 0.566 p 0.04).

Discussion

In this study, we described for the first time (i) IgE autoantibodies against eosinophil human proteins in children and adults; (ii) Basophil activation mediated by anti-EPX IgE and anti-ECP IgE; (iii) IgE and IgG autoantibodies against eosinophil proteins could be a biomarker of lung function in asthmatic patients.

In childhood, the eosinophilic endotype is frequent and different biomarkers in sputum or bronchopulmonary lavage have been proposed to detect this endotype of T2 response. However, less invasive methods have been used in children and blood eosinophils are the most common biomarker used to indicate the presence of predominantly eosinophilic asthma, but its specificity is low, as we could see in this study where there was no difference in the levels of blood eosinophils between the group with asthma and the control group.25,26 The exploration of autoantibodies may be a starting point for new biomarker options of new biomarkers that allow improving the diagnosis, treatment selection and prognosis of patients. Of the 4 autoantibodies studied, anti-EPX IgE had the highest specificity for the group with asthma, which suggests that it could be useful for the diagnosis of the disease and could be signaling a new endotype with a T2 response but mediated by an autoimmune mechanism. The two IgE autoantibodies (anti-EPX/ECP IgE) were associated with lower lung function, which would indicate their usefulness as possible biomarkers of severity. In the case of IgG autoantibodies, although it was not statistically significant, similar to IgE autoantibodies, there was a tendency to be found more frequently in the group of patients with asthma and also to be present in patients with lower lung function, so that their usefulness as biomarkers cannot be ruled out.

Allergic and autoimmune response are part of a spectrum of immunological diseases and their involvement in the pathogenesis of asthma has been proposed based on presence of immunoglobulins against diverse environmental antigens and self-antigens.21 However, the presence of antibodies or autoantibodies does not necessarily have a clinical impact or relevance in the pathogenesis of a disease. As have been observed with other allergens and auto-allergens, in both groups (asthma and healthy controls) the presence of IgE and IgG antibodies was observed. However, the median levels of these autoantibodies in the asthmatic group was higher than control group and basophil activation even in low concentrations was only present in asthmatic patients, suggesting that these autoantibodies are functional and inflammatory activity could participate in the pathogenesis of the disease.

Compared with other allergic and non-allergic diseases,11,27,28 the role of IgE autoantibodies in asthma has not been studied in detail so far. In general, basophils in the control group presented lower percentages of activation compared to asthmatic patients, however we observed activation using the highest concentration (1  μg/mL). Due to the enzymatic nature of EPX and ECP, a nonspecific degranulation could be the explanation for these results, but this hypothesis needs to be confirmed.

Recently, we described anti-EPEX and Anti-ECP IgE in patients with urticaria and atopic dermatitis,17 so these autoantibodies are no pathognomonic for asthma. These 3 diseases have in common elevated levels of IgE and eosinophils in serum and/or local tissue (Skin or lung respectively). In atopic dermatitis the levels of anti-EPX/ECP were three times higher than in urticaria or asthma. This suggests that the intensity of type 2 inflammation increase the probability of IgE autoimmunity.

Some previous studies suggest that IgG autoimmune response in asthma is present especially in non-atopic asthmatic patients with severe clinical presentations.29, 30, 31, 32, 33, 34 For most of IgG autoantibodies the clinical relevance is unknown and studies evaluating its role in the pathogenesis of asthma are necessary. However, some IgG autoantibodies have been associated with the severity of asthma and the use of high doses of steroids, therefore it could have an important clinical impact.21 Anti-EPX IgG was previously reported in the sputum of 24/65 (37%) asthmatics;6 we observed a similar frequency of anti-EPX IgG (25.4%) in asthmatic patients that was higher than control group but not statistically significant. The higher frequency of IgG autoantibodies, especially in the most severe cases, regardless of age, suggests that their formation is associated with the intensity of the inflammatory process and could potentially serve as biomarkers of severity.

IgE autoantibodies in asthma has been little studied7,35,36 compared with other chronic diseases.11,12,27,28,37, 38, 39 The origin of these autoantibodies is unclear; In some cases, it seems to be secondary to cross-reactivity with environmental proteins,40 in others it seems to be the result of a high exposure of antigens usually hidden in a medium with a high number of inflammatory mediators.41, 42, 43, 44, 45, 46 This may occur with EPX and ECP antigens when they are released by eosinophils during inflammatory process in atopic dermatitis, urticaria, and asthma.17,47, 48, 49, 50, 51

Unlike other studies, we observed that blood eosinophil count and total IgE were high compared with other populations such as Europeans, both in the asthmatic group and in the control group. The study population is located in a tropical area where parasite exposure is endemic; therefore, this stimulus could influence the high levels found of both eosinophils and total IgE.4,52 However, at the time of the study none of the subjects had active parasitosis infection. Despite EPX and ECP are both being produced by eosinophils during the inflammatory response, there was no correlation among the anti-ECP IgE and anti-EPX IgE levels, suggesting that although they are released by the same cell and probably their antigenic presentation occurs at the same time and context; the intensity and frequency of the IgE response to each antigen have different triggers.

The study has some limitations; The sample size was calculated to detect autoantibodies in patients with asthma; therefore, other analyses are only exploratory, for example to assess the association with asthma severity. However, the descriptive data obtained are useful as a starting point for further studies.

Conclusions

We demonstrated IgE autoantibodies against eosinophil proteins EPX and ECP in adults and children. These antibodies can induce an inflammatory response and appear to be related to severe asthma. The detection of autoantibodies could have clinical implication in the diagnosis and therapeutic approach; therefore, more studies are necessary to evaluate its diagnostic performance and its possible usefulness as a predictor of severity.

Abbreviations

ECP, Eosinophil cationic protein; EPX, Eosinophil peroxidase; FVC, Forced vital capacity, FEV1, Forced expiratory volume; OD, optical density units.

Funding

This article is the result of the project "Identification of modifiable risk factors related to the severity of asthma and the development of atopy in the pediatric population of Antioquia” Code "2016-12948, CII-07". We thank the "IPS Universitaria” Clinic, and the University of Antioquia, for their logical support and for financing this project.

Authors’ contribution

JS contributed the central idea. JL and JS evaluated and collected clinical data from patients. JL, MM, and AS organized the databases. JS, AS, EG and MM analyzed the data. JS, AS, and JL wrote the first draft. All authors were involved in writing, reviewing, and editing the final manuscript.

Ethical approval

The Ethics committees of University of Antioquia approved the study (Code CII-07 2016). Written informed consent was obtained from all the participants or in the case of children, it was obtained from their parents.

Authors’ consent for publication

All authors have approved the submission of this manuscript. These results have not been previously published in another journal.

Data availability statement

The datasets generated for this study are available on request to the corresponding author.

Declaration of competing interest

Authors have not conflict of interest to declare.

Acknowledgments

We thank the University of Antioquia and Clinic “IPS Universitaria” for their financial and logistical support.

Footnotes

Full list of author information is available at the end of the article

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated for this study are available on request to the corresponding author.

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