







































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: s.tubek@szpital.opole.pl; 
 
Cite as: Warmuzińska, Alina, Dariusz Woszczyk, and Sławomir Tubek. 2024. “Clinical Picture of Patients With the 
Undetectable Serum IgE and Low Serum IgE in a Retrospective Evaluation of Patients of the Opole Regional Hospital (2013-
2023)”. Asian Journal of Immunology 7 (1):112-22. https://journalaji.com/index.php/AJI/article/view/136. 
 

 
 

Asian Journal of Immunology 
 
Volume 7, Issue 1, Page 112-122, 2024; Article no.AJI.120841 
 

 
 

 

 

Clinical Picture of Patients with the 
Undetectable Serum IgE and Low 

Serum IgE in a Retrospective 
Evaluation of Patients of the Opole 

Regional Hospital (2013-2023) 
 

Alina Warmuzińska a, Dariusz Woszczyk b  

and Sławomir Tubek b* 
 

a Department of Imaging Diagnostics, Regional Hospital in Opole, Opole, Poland. 
b Clinical Department of Haematology, Faculty of Medicine, Haematological Oncology and Internal 

Medicine, Regional Hospital in Opole, University of Opole, Opole, Poland. 
 

Authors’ contributions  
 

This work was carried out in collaboration among all authors. All authors read and approved the final 
manuscript. 

 
Article Information 

 
DOI: https://doi.org/10.9734/aji/2024/v7i1136  

 
Open Peer Review History: 

This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer 
review comments, different versions of the manuscript, comments of the editors, etc are available here: 

https://www.sdiarticle5.com/review-history/120841 
 
 
 

Received: 05/06/2024 
Accepted: 06/08/2024 
Published: 10/08/2024 

 
 
ABSTRACT 
 

Over the period 01/01/2013 until 31/08/2023, 13 907 total plasma IgE determinations were 
performed in the analytical laboratory of the Provincial Hospital in Opole. 
Among these determinations, there were 377 results below 2.0 U/l (in 279 patients), with the ultra-
extremely low results (<0.1 U/l), i.e. virtually undetectable, in 65 (in 44 patients).  

Original Research Article 

https://doi.org/10.9734/aji/2024/v7i1136
https://www.sdiarticle5.com/review-history/120841


 
 
 
 

Warmuzińska et al.; Asian J. Immunol., vol. 7, no. 1, pp. 112-122, 2024; Article no.AJI.120841 
 
 

 
113 

 

The clinical picture of patients with the ultra-extremely low (undetectable) IgE (defined as <0.1 U/l) - 
group 1 and the low IgE (defined as <2.0 U/l), divided into 4 ranges - 0.1-0.5; 0.6 -1.0; 1.1-1.5; 1.6-
1.9 U/l - the group 2, 3, 4 and 5 respectively - was compared. 
Results: Health problems, defined as a syndrome of immune dysfunction, occurred more frequently 
in the groups with the ultra-low (virtually undetectable) IgE (<1.0) than in the group with the low IgE 
(0.1 - 1.9) level, suggesting primary immune deficiency in these patients. This is also supported by 
the fact that the group 1 was younger than the others combined, and at the same time ‘sicker’ than 
the other groups. 
In this group - 97 patients had serum IgE determinations at least twice during the analysed period - 
in 20 patients at least one of the repeated serum IgE results was higher than 10 U/l, in the 
remaining ones - in 17 patients it was in the range (2-10 U/l), in the remaining 60 patients the 
results of repeated serum IgE determinations did not exceed 2 U/l. 
Conclusions: For the purpose of talking about IgE deficiency as an indicator of a predisposition to 
neoplastic diseases, it would be necessary to carry out screening tests at least 3 times, in the 
identified age groups, e.g. every 10 years, from the age of 5 years. 
This would make it possible to determine - whether the IgE deficiency is primary or secondary. 
Primary, i.e. originally predisposing to the development of neoplastic diseases and being a part of 
primary immunodeficiency, or secondary - as a symptom of ‘depletion’ of the immune system. 
The incidentally detected low serum IgE needs to be verified. 
 

 

Keywords: Ultralow/undetectable IgE plasma level (<0.1 U/l); extremely low IgE plasma level (<2.0 
U/l); low IgE plasma level. 

 

1. INTRODUCTION 
 

Interest in the significance of low plasma total 
IgE levels has been growing in the recent years 
due to data demonstrating its relationship to 
immunodeficiency syndromes and susceptibility 
to neoplastic diseases [1-6].  In both cases, there 
is a broad concept of immune dysfunction 
syndrome. High levels of total IgE, in turn, are 
thought to improve a prognosis in the selected 
groups of oncology patients. Furthermore, there 
are emerging perspectives for the use of allegro-
oncological knowledge in the oncology treatment 
processes and the side effects of immunotherapy 
of neoplastic diseases [7-10].  
 

Awareness of differences in response to 
treatment depending on blood IgE levels may 
influence the individualisation of treatment for the 
specific conditions [11]. 
 

The reference value for plasma IgE levels is 
values below 100 U/l - 2-100 U/l. In the literature, 
values below 2.0 - 2.5 U/l are considered low or 
extremely low levels of total IgE. 
 

As the group of individuals with total IgE values 
below 2.0 - 2.5 U/l may be clinically significantly 
heterogeneous due to the presence of tissue IgE, 
it is suggested that IgE values below this limit 
should be more accurately determined [5]. 
 
In a previous study comparing a group with the 
ultra-extremely low IgE level (<0.1 U/l), i.e. 

virtually undetectable, with a group with the 
extremely high IgE level (>10,000 U/l), a 
proposal was made that the IgE values <0.1 U/l 
should be defined as the ultra-extremely low (or 
undetectable), values between 0.1 and 0.5 as 
the extremely low and values between 0.6 and 
2.0 as the low ones [12].  
 
In the retrospective study presented here, it was 
decided to compare the groups clinically - with 
the ultra-extremely low IgE levels (<0.1 U/l), i.e. 
virtually undetectable and the low IgE (defined 
as >0.1 to <2.0 U/l). 
 

2. MATERIALS AND METHODOLOGY 
 

Within the period 01/01/2013 until 31/08/2023, 
13 907 total plasma IgE determinations were 
performed in the analytical laboratory of the 
Provincial Hospital in Opole. 
 

Assuming the data quoted above, among these 
determinations there were 377 results below 2.0 
U/l (in 279 patients), while the ultra-extremely low 
results (<0.1 U/L), i.e. practically undetectable, 
were 65 (in 44 patients).  
 

A comparison was decided to be made between 
the clinical picture of patients with the ultra-
extremely low (undetectable) IgE (defined as 
<0.1 U/l) - the group 1 and the low IgE (defined 
as <2.0 U/l), divided into 4 ranges - 0.1-0.5; 0.6 -
1.0; 1.1-1.5; 1.6-1.9 U/l - the groups 2, 3, 4 and 5 
respectively. 



 
 
 
 

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114 

 

3. RESULTS 
 
In order to compare the study samples, statistical 
analyses were performed using the IBM SPSS 
Statistics 29. The analyses used included 
Student's t-test for independent samples, one-
way analysis of variance and chi-square test of 
independence. The significance level was taken 
as the threshold α = 0.05, the effect size was 
interpreted according to Cohen (Cohen, J.,1992. 
A power primer. Psychological Bulletin,           
112(1), 155–159. https://doi.org/10.1037/0033-
2909.112.1.155).  
 
In the first instance, differences between all 
compared groups were calculated for nominal 
variables using the chi-square test of 
independence (Table 1) and for the age using 
one-way analysis of variance (Fig. 1). When 
differences were observed with the chi-square 
test, the significance of the differences was 
calculated using the Bonferroni correction for 
multiple pairwise comparisons. Parameters 
assessed were age, sex, place of hospitalisation 
(suggesting the most significant health problem), 
prevalence of bronchial asthma/chronic 
obstructive pulmonary disease (COPD), 
neoplastic disease including lymphoma, immune 
dysfunction syndrome, atopic dermatitis (AD), 
bronchiectasis, sarcoidosis, psoriasis, 
granulomatosis with polyangiitis (formerly known 
as Wegener's granulomatosis). 
 
Analysis of the differences in terms of individual 
nominal variables (Table 1), revealed a lack of 

statistically significant differences for sex and 
individual, and no differences were observed in 
the frequency of diseases such as lymphoma, 
sarcoidosis, psoriasis and granulomatosis with 
polyangiitis. Bronchial asthma was found to be 
the least frequent in group 5 (approx. 21%) 
compared to the group 3 (approx. 43%), where it 
occurred most frequently. The groups 1, 2, 4 
were intermediate in terms of the number of 
people experiencing asthma (approx. 31%) and 
did not differ from the extreme groups. Similarly, 
neoplastic disease, irrespective of the starting 
point, was most common in the group 3 (approx. 
44%) compared to group 5 (approx. 16%), while 
no differences were observed in the other groups, 
with the rates of neoplastic diseases ranging 
from 26% to 36%. Immune dysfunctions were 
less frequent in the groups 4 (approx. 31%) and 
5 (approx. 13%) compared to the groups 1, 2 
and 3, where the percentage of dysfunctions was 
approx. 90%. Analysing the results in terms of 
AD, it was found that the condition was most 
common in the group 2 (approx.  12%) compared 
to the group 5, where it was not present at all 
(0%), the other groups ranged from 1% to 6% 
and did not differ from the extreme groups. 
Bronchiectasis in turn, was observed most 
frequently in the group 1 (approx. 23%) and least 
frequently in group 5 (approx. 3%), while no 
significant differences were observed in the other 
groups and, on average, this condition occurred 
in 10% of individuals. Additional analysis also 
showed that there were no statistically significant 
differences in the age of the groups compared, 
F(4.318) = 1.66; p = 0.160; η2 = 0.02 (Fig. 1). 

 

 
 

Fig. 1. Age differentiation in the groups compared (Key: Wiek-Age, Grupa-Group) 
Annotation. Bars for errors represent 95% confidence intervals of mean scores 

Grupa 1 Grupa 2 Grupa 3 Grupa 4 Grupa 5
54

56

58

60

62

64

66

68

70

W
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k



 
 
 
 

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Table 1. Clinical parameters evaluated in each group of patients: with the ultra-extremely low (undetectable) IgE (defined as <0.1 U/l) - the group 1 
and the low IgE (defined as <2.0 U/l), divided into 4 ranges - 0.1-0.5; 0.6 -1.0; 1.1-1.5; 1.6-1.9 U/l - the groups 2, 3, 4 and 5, respectively 

 

Differentiation of the study groups in terms of the variables tested 
Variable  Group 1 Group 2 Group 3 Group 4 Group 5 χ2 df p V 
Sex M 18 (0.41) 23 (0.39) 19 (0.26) 33 (0.41) 24 (0.35) 4.53 4 0.339 0.12 
 K 26 (0.59) 36 (0.61) 53 (0.74) 47 (0.59) 44 (0.65)     

Unit OP 30 (0.68) 38 (0.64) 54 (0.75) 54 (0.68) 50 (0.74) 21.46 16 0.161 0.13 
 OD 3 (0.07) 8 (0.14) 3 (0.04) 7 (0.09) 6 (0.09)     

 OH 8 (0.18) 9 (0.15) 13 (0.18) 10 (0.13) 6 (0.09)     

 OCW 0 (0.00) 4 (0.07) 1 (0.01) 2 (0.03) 1 (0.01)     

 Other 3 (0.07) 0 (0.00) 1 (0.01) 7 (0.09) 5 (0.07)     

Asthma/COPD No 34 (0.77) 40 (0.68) 41 (0.57) 50 (0.63) 54 (0.79) 10.92 4 0.027 0.18 
 Yes 10 (0.23) 19 (0.32) 31 (0.43) 30 (0.38) 14 (0.21)     

Neoplastic disease No 32 (0.73) 38 (0.64) 40 (0.56) 59 (0.74) 57 (0.84) 14.90 4 0.005 0.21 
 Yes 12 (0.27) 21 (0.36) 32 (0.44) 21 (0.26) 11 (0.16)     

Lymphoma No 38 (0.86) 50 (0.85) 57 (0.79) 68 (0.85) 56 (0.82) 1.48 4 0.830 0.07 
 Yes 6 (0.14) 9 (0.15) 15 (0.21) 12 (0.15) 12 (0.18)     

Immunological dysfunctions No 4 (0.09) 7 (0.12) 10 (0.14) 55 (0.69) 59 (0.87) 144.54 4 <0.001 0.67 
 Yes 40 (0.91) 52 (0.88) 62 (0.86) 25 (0.31) 9 (0.13)     

AD No 42 (0.95) 52 (0.88) 68 (0.94) 79 (0.99) 68 (1.00) 13.25 4 0.010 0.20 
 Yes 2 (0.05) 7 (0.12) 4 (0.06) 1 (0.01) 0 (0.00)     

Bronchiectasis No 34 (0.77) 55 (0.93) 60 (0.83) 75 (0.94) 66 (0.97) 16.83 4 0.002 0.23 
 Yes 10 (0.23) 4 (0.07) 12 (0.17) 5 (0.06) 2 (0.03)     

Sarkoidosis No 42 (0.95) 54 (0.92) 67 (0.93) 72 (0.90) 64 (0.94) 1.66 4 0.799 0.07 
 Yes 2 (0.05) 5 (0.08) 5 (0.07) 8 (0.10) 4 (0.06)     

Psoriasis No 44 (1.00) 56 (0.95) 71 (0.99) 77 (0.96) 67 (0.99) 3.95 4 0.412 0.11 
 Yes 0 (0.00) 3 (0.05) 1 (0.01) 3 (0.04) 1 (0.01)     

Granulomatosis with 
polyangiitis 

No 41 (0.93) 54 (0.92) 69 (0.96) 76 (0.95) 66 (0.97) 2.35 4 0.671 0.09 

 Yes 3 (0.07) 5 (0.08) 3 (0.04) 4 (0.05) 2 (0.03)     
Annotation. n(%) - number of observations (percentage of observations); χ² - result of a chi-square test; df - number of degrees of freedom; p - statistical significance; V - effect 

size. OP – pulmonology department, OD – dermatology department, OH – haematology department, OCW – internal diseases department 
 



 
 
 
 

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Table 2. Clinical parameters evaluated in each patient group: with ultra-extremely low (undetected) IgE (defined as <0.1 U/l) - the group 1 and low 
IgE (defined as <2.0 U/l), divided into 4 ranges - 0.1-0.5; 0.6 -1.0; 1.1-1.5; 1.6-1.9 U/l - the groups 2, 3, 4 and 5 respectively (this time a total of 2-5) 

 

Contrast analysis of the groups studied in terms of the variables tested  

Variable  Group 1 Groups 2-5 χ2 df p φ/V 
Sex Men 18 (0.41) 99 (0.35) 0.48 1 0.487 0.04 
 Women 26 (0.59) 180 (0.65)     

Unit OP 30 (0.68) 196 (0.70) 2.34 4 0.673 0.09 
 OD 3 (0.07) 24 (0.09)     

 OH 8 (0.18) 38 (0.14)     

 OCW 0 (0.00) 8 (0.03)     

 Other 3 (0.07) 13 (0.05)     

Asthma No 34 (0.77) 185 (0.66) 2.09 1 0.148 0.08 
 Yes 10 (0.23) 94 (0.34)     

Neoplastic disease No 32 (0.73) 194 (0.70) 0.18 1 0.668 0.02 
 Yes 12 (0.27) 85 (0.30)     

Lymphoma No 38 (0.86) 231 (0.83) 0.35 1 0.556 0.03 
 Yes 6 (0.14) 48 (0.17)     

Immunological dysfunctions No 4 (0.09) 131 (0.47) 22.40 1 <0.001 0.26 
 Yes 40 (0.91) 148 (0.53)     

AD No 42 (0.95) 267 (0.96) 0.01 1 0.941 <0.01 
 Yes 2 (0.05) 12 (0.04)     

Bronchiectasis No 34 (0.77) 256 (0.92) 8.69 1 0.003 0.16 
 Yes 10 (0.23) 23 (0.08)     

Sarcoidosis No 42 (0.95) 257 (0.92) 0.62 1 0.432 0.04 
 Yes 2 (0.05) 22 (0.08)     

Psoriasis No 44 (1.00) 271 (0.97) 1.29 1 0.255 0.06 
 Yes 0 (0.00) 8 (0.03)     

Granulomatosis with polyangiitis No 41 (0.93) 265 (0.95) 0.25 1 0.619 0.03 
 Yes 3 (0.07) 14 (0.05)     

Annotation. n(%) – number of observations (percentage of observations); χ² - result of a chi-square test; df - number of degrees of freedom; p - statistical significance; V - effect 
size for the tables larger than 2x2. 

Abbreviations – OP – pulmonology department, OD – dermatology department, OH – haematology department, OCW – internal diseases department 

 



 
 
 
 

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Table 3. Characteristics of individual patients with the incidentally low serum IgE <2.0 U/l who had more than one IgE determination during the 
study period and at least one of the determinations was higher than 10 U/l 

 

 Sex/age at the 
time the ultra-low 
level of IgE was 
determined 

Health problems according to  
medical records 

Number of the IgE 
determinations and a range of 
values 

Main (most frequent) 
place of hospitalisation 
/ treatment 

1 K 69 Microcellular carcinoma of the right lung, decrease in the 
IgE level during dissemination - can be interpreted as a 
symptom of depletion of the immune system 

3x 
0.4 – 345, chronologically: 
187 – 345 0.4 

OP 

2 K 73 Adenocarcinoma of the right lung - subsequent progression 
- metastasis to the left lung and adrenal glands; chronic 
obstructive pulmonary disease (COPD), renal cysts - can 
be interpreted as a symptom of immune depletion 

2x 
0.5 – 218.7, 
chronologically: 
218.7 – 0.5 

OP 

3 K 81 Granulomatosis with polyangiitis (Wegener 
granulomatosis), bronchial asthma, chronic sinusitis, 
venous insufficiency of the lower limbs - can be interpreted 
as a symptom of depletion of the immune system 

9x 
0.5 – 82.6, 
chronologically: 
82.6 – 1.1 -0.5 

OP 

4 K 85 Non-small cell cancer of the right lung, lower limb venous 
thrombosis, atrial fibrillation, old age - can be interpreted as 
a symptom of immune system depletion 

2x 
0.7– 12.5, 
chronologically: 
12.5 – 0.7 

OP 

5 K 86 Granulomatosis with polyangiitis (Wegener 
granulomatosis), tuberculosis in anamnesis, osteoporosis, 
degenerative changes of the musculoskeletal system, 
pnemocystodosis - can be interpreted as a symptom of 
depletion of the immune system 

4x 
0.7 – 92.1, 
chronologically: 
92.1 – 3.7 -   1.1 – 0.7 

OP 

6 K 73 Tumour of the left lung, bronchial asthma / COPD, 
emphysema, generalised atherosclerosis - can be 
interpreted as a symptom of depletion of the immune 
system 

2x 
73.3 – 0.8 

OP 

7 M 86 Granulomatosis with polyangiitis (Wegener 
granulomatosis), purulent arthritis, multilevel discopathy - 
can be interpreted as a symptom of depletion of the 
immune system 

2x 
1.1- 91.1 
chronologically: 92.1 – 3.7 – 1.1 

OP 



 
 
 
 

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118 

 

 Sex/age at the 
time the ultra-low 
level of IgE was 
determined 

Health problems according to  
medical records 

Number of the IgE 
determinations and a range of 
values 

Main (most frequent) 
place of hospitalisation 
/ treatment 

9 M 73 Left lung tumour. Bronchial asthma/COPD, emphysema, 
generalised atherosclerosis – can be interpreted as a 
symptom of depletion of the immune system 

2x 
73.3 – 0.8 

OP 

11 M 53 Tuberculosis recurrence, COPD, emphysema, fluid in left 
pleural cavity - increase in the IgE level during clinical 
improvement phase 

2x 
1.3 - 144 

OP 

12 M 71 Post-radiation pneumonia 
Small cell cancer of the right lung, bronchial asthma, atrial 
fibrillation, circulatory failure - increase in the IgE level 
during clinical improvement phase 

2x 
1.4 – 107.7 

OP 

13 K 73 COPD/Bronchial asthma, psoriasis - last highest result 
during the period of requiring hospitalisation for 
exacerbation of bronchial asthma and psoriasis; high 
variability of IgE levels - indicates significant lability of the 
immune system 

13x 
1.4 - 1200 

OP 

14 M 83 Bronchiolitis, idiopathic bronchiolitis with organising 
pneumonia, bronchial asthma, secondary 
immunodeficiency, generalised atherosclerosis 

7x 
1.5 - 13 

OP 

15 K 81 COPD, emphysema, chronic respiratory failure on home 
oxygen therapy, Graves-Basedow disease – can be 
interpreted as a symptom of depletion of the immune 
system 

7x 
101.2 – 1.4 

OP 

16 M 56 Pulmonary sarcoidosis, chronic renal failure, chronic 
venous insufficiency of the lower limbs 

3x 
38.6-1.6-24.0 

OP 

17 K 81 Tumour of the right lung, COPD, t2 DM - without 
histopathological diagnosis of the tumour, stable clinical 
condition 

2x 
1,6 – 47,4 

OP 

18 M 68 Idiopathic pulmonary fibrosis, chronic respiratory failure on 
home oxygen therapy, bronchiectasis, t2 DM, secondary 
immunodeficiency, listeriosis in anamnesis - increase in the 
IgE level during inflammatory exacerbation of chronic 

3x 
0,9 – 16,0 – 1,6 

OP 



 
 
 
 

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 Sex/age at the 
time the ultra-low 
level of IgE was 
determined 

Health problems according to  
medical records 

Number of the IgE 
determinations and a range of 
values 

Main (most frequent) 
place of hospitalisation 
/ treatment 

respiratory failure 
19 K 71 Adenocarcinoma of the right lung 

Bronchial asthma - increase in the IgE level during asthma 
exacerbation 

2x 
1,8 – 485,5 

OP 

20 M 48 Granulomatosis with polyangiitis (Wegener 
granulomatosis), granulomatous otitis media, t2 DM - 
decrease in the IgE level during the period of clinical 
improvement 

4x 
27,4 – 0,4 

OP 

OP – pulmonology department, COPD – chronic obstructive pulmonary disease, t2 DM- type 2 diabetes mellitus 
 

 
 

Fig. 2. Analysis of contrast in terms of age differences (Key: Wiek-Age, Grupa-Group) 
Annotation. Bars for errors represent 95% confidence intervals of mean scores. 

Grupy 2-5 Grupa 1
56

58

60

62

64

66

68

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In the next step, a contrast analysis was 
performed between the group 1 and the 
aggregated results of the group 2 - 5. A 
comparison of nominal indicators was performed 
using the chi-square test of independence, and 
the results are presented in the Table 2. A 
comparison of ages was performed using the 
Student's t-test for independent samples, and the 
results are presented in the Fig. 2. 
 
The analyses performed (Table 2), showed that 
only the presence of immune dysfunctions and 
bronchiectasis demonstrated statistically 
significant differences. Immune dysfunctions 
were present in 91% of subjects in the group 1, 
while in the groups 2 - 5, just over 50% of 
subjects were observed to have immune 
dysfunctions. In the case of bronchiectasis, the 
prevalence of this condition was observed to be 
significantly higher for the group 1 (approx. 23%) 
compared to the groups 2-5 (approx. 8%). 
Furthermore, it appeared that those in groups 2-
5 were older by an average of six years 
compared to those in the group 1, t(321) = 2.17 
95% CI [0.57; 11.88]; p = 0.031; d = 0.35 (Fig. 2). 
 
In the material under study, serum IgE 
determinations were not part of routine, repeated 
testing. Hence, in some individuals, the serum 
IgE was determined once, in spite of several 
hospitalisations or visits to hospital outpatient 
clinics, in others repeatedly (97 of 323 patients). 
 
In this group of 97 patients (with at least one IgE 
result <2.0 U/l) - in 20 patients at least one of the 
repeated serum IgE results was higher than 10 
U/l (Table 3), of the remainder - in 17 patients it 
was in the range (2-10 U/l), in the remaining 60 
the repeated serum IgE level determinations did 
not exceed 2 U/l. 
 
4. DISCUSSION 
 
As mentioned above - the analysis of differences 
in terms of individual nominal variables (Table 1), 
revealed a lack of statistically significant 
differences in respect of sex and individual, and 
in addition no differences were observed in the 
frequency of diseases such as lymphoma, 
sarcoidosis, psoriasis and granulomatosis with 
polyangiitis. Bronchial asthma appeared to occur 
least frequently in the group 5 (approx. 21%) 
compared to the group 3 (approx. 43%), where it 
occurred most frequently. The groups 1, 2, 4 had 
intermediate numbers of people experiencing 
asthma (approx. 31%) and did not differ from the 
extreme groups. Similarly, neoplastic disease, 

irrespective of the starting point, was most 
common in the group 3 (approx. 44%) compared 
to the group 5 (approx. 16%), while no 
differences were observed in the other groups, 
where the percentage of neoplastic diseases 
ranged from 26% to 36%. Immune dysfunctions 
were less frequent in the groups 4 (approx. 31%) 
and 5 (approx. 13%) compared to the groups 1, 
2 and 3, where the percentage of dysfunctions 
reached approximately 90%. 
 
This supports the idea that the lower the serum 
IgE level, the greater the probability of immune 
dysfunction.  Bronchiectasis, on the other hand, 
was observed most frequently in the group 1 
(approx. 23%) and least frequently in the group 5 
(approx. 3%), while no significant differences 
were observed in the other groups and, on 
average, this condition occurred in 10% of 
individuals. The distinctly more frequent 
occurrence of bronchiectasis in the group 1 
indicates an impairment of the immune response 
to bacterial infections of the respiratory tract, 
which resulted in prolonged inflammation of the 
bronchi and destruction of the bronchial wall. 
 
An additional analysis also showed that there 
were no statistically significant differences in 
terms of the age of the groups under comparison, 
F(4.318) = 1.66; p = 0.160; η2 = 0,02 (Fig. 1). 
 
The analyses comparing the group 1 with the 
groups 2-5 combined (Table 2), showed that only 
the presence of immunological dysfunctions and 
bronchial dilatation showed statistically 
significant differences. It turned out that immune 
dysfunction was present in 91% of the group 1 
subjects, while in the groups 2-5, just over 50% 
of subjects were observed to have immune 
dysfunction. In the case of bronchiectasis, the 
prevalence of this condition was observed to be 
significantly higher for the group 1 (approx. 23%) 
compared to the groups 2-5 (approx. 8%). 
Moreover, it appeared that people in the groups 
2-5 were older by an average of six years 
compared to those in the group 1, t(321) = 2.17 
95% CI [0.57; 11.88]; p = 0.031; d = 0.35 (Fig. 2). 
 
Health issues, defined as a syndrome of immune 
dysfunction, were more common in the groups 
with the ultra-low (virtually undetectable) IgE 
level (<1.0) than in the group with the low IgE 
level (0.1 - 1.9), suggesting primary immune 
deficiency in these patients. This is also 
supported by the fact that the group 1 was 
younger than the others combined, but at the 
same time ‘sicker’ than the other groups. 



 
 
 
 

Warmuzińska et al.; Asian J. Immunol., vol. 7, no. 1, pp. 112-122, 2024; Article no.AJI.120841 
 
 

 
121 

 

Based on these observations, one can try to 
answer the question: 
 
Randomly found the low serum IgE - IgE 
deficiency - primary or secondary? 
 
For the purpose of referring to IgE deficiency as 
an indicator of predisposition to neoplastic 
diseases [1-6], screening should be carried out 
at least 3 times, in the specific age groups, e.g. 
every 10 years, beginning at 5 years of age. 
 

This would also make it possible to determine - 
whether the IgE deficiency is primary or 
secondary. Primary, i.e. originally predisposing to 
the development of neoplastic diseases and 
forming part of the primary immunodeficiency, or 
secondary - as a symptom of ‘depletion’ of the 
immune system. 
 

The low serum IgE determined randomly 
requires a verification. 
 

In the delimited group with the low IgE level, 
additional skin tests can be conducted to 
evaluate a deficiency of the tissue Ig [13,14]. 
 

In the material under study, determinations of the 
serum IgE were not part of routine, repeated 
testing. Thus, in some patients, the serum IgE 
was determined once, despite several 
hospitalisations or visits to the hospital outpatient 
clinics, in others it was determined repeatedly 
(97 of 323 patients). In this group of 97 patients - 
in 20 patients at least one of the repeated serum 
IgE results was higher than 10 U/l (Table 3), of 
the others - in 17 patients it was in the range (2-
10 U/l), and in the remaining 60 patients 
repeated determinations of the serum IgE levels 
did not exceed 2 U/l. 
 

This observation may suggest that the IgE levels 
<0.1 U/l, found randomly, are more suggestive of 
primary immunodeficiency than levels between 
0.1 and 2.0 U/l, where they are more probably 
suggestive of secondary immunodeficiency. 
 

5. CONCLUSION 
 

The low serum IgE level found incidentally does 
not allow to conclude whether the IgE deficiency 
is primary or secondary (as a symptom of 
‘depletion’ of the immune system), and can be 
considered a poor prognostic factor, e.g. in 
chronic lymphocytic leukaemia [15].  Its                 
increase in subsequent studies argues for the                   
secondary nature of a previous low level,                    
but it can be considered a positive                 

prognostic factor for regression of the underlying 
disease. 
 

DISCLAIMER (ARTIFICIAL INTELLIGENCE) 
 
Authors hereby declare that NO generative AI 
technologies such as Large Language Models 
(ChatGPT, COPILOT, etc) and text-to-image 
generators have been used during writing or 
editing of manuscripts.  
 

COMPETING INTERESTS 
 
Authors have declared that no competing 
interests exist. 
 

REFERENCES 
 
1. Patel MB, Smith JK, Chi DS, 

Krishnaswamy G, Regulation and 
dysregulation of immunoglobulin E: A 
molecular and clinical perspective. Clinical 
and Molecular Allergy (CMA) 2010;8:3.  
Available:http://www.clinicalmolecularallerg
y.com/content/8/1/3 

2. Lawrence MG, Palacios-Kibler TV, 
Workman LJ, Schuyler AJ, Steinke JW, 
Payne SC, McGowan SC, Patrie J, 
Fuleihan RL, Sullivan KE, Lugar PL, 
Hernandez CL, Beakes DE, Verbsky JW, 
Platts-Mills TAE, Cunningham-Rundles Ch, 
Routes JM, Borisch L. Low Serum IgE Is 
a Sensitive and Specific Marker for 
Common Variable Immunodeficiency 
(CVID). J Clin Immunol. 2018;38(3):225-33. 
DOI: 10.1007/s10875-018-0476-0 

3. Matricardi PM, The Very Low IgE Producer: 
Allergology, Genetics, Immunodeficiencies, 
and Oncology. Biomedicines.2023;11:1378.  
Available:https://doi.org/10.3390/biomedici
nes11051378  

4. Ferastraoaru  DH, Bax J, Bergmann C, 
Capron M, Castells M, Dobrowicz D, 
Fiebiger E, Gould HJ, Hartmann K, Jappe 
U, Jardakieva G, Josephs DH, Levi-
Schaffer F, Mahler V, Poli A, Rosensterich 
D, Roth-Walter F, Shamji M, Steveling-
Klein EH, Turner MC, Untersmayrs E, 
Karagiannis SN, Jensen-Jarolim E , 
AllergoOncology: ultralow IgE, a potential 
novel biomarker in cancer—a Position 
Paper of the European Academy of Allergy 
and Clinical Immunology (EAACI). Clin 
Transl Allergy. 2020; 10:32. 
Available:https://doi.org/10.1186/s13601-
020-00335-w 



 
 
 
 

Warmuzińska et al.; Asian J. Immunol., vol. 7, no. 1, pp. 112-122, 2024; Article no.AJI.120841 
 
 

 
122 

 

5. Ferastraoarua D, Jordakieva G, Jensen-
Jarolim E, The other side of the coin: IgE 
deficiency, a susceptibility factor for 
malignancy occurrence. World Allergy 
Organization Journal 2021;14:100505 
Available:http://doi.org/10.1016/j.waojou.20
20.100505.eCollection 2021 Jan.   

6. Ferastraoaru D, Rosenstreich D,  IgE 
deficiency and prior diagnosis of 
malignancy: Results of the 2005-2006 
National Health and Nutrition Examination 
Survey. Ann Allergy Asthma Immunol. 2018; 
121(5):613-618.  
DOI: 10.1016/j.anai.2018.07.036.  
Epub 2018 Aug 4. PMID: 30086407  

7. Wang A, Wan P, Hebert JR, Atopic allergic 
conditions and prostate cancer risk and 
survival in the Multiethnic Cohort study. 
British Journal of Cancer. 2023;129:974–
981;  
Available:https://doi.org/10.1038/s41416-
023-02364-1 

8. McCraw AJ, Chauhan J, Bax HJ, Stavraka 
C, Osborn G, Grandits M, López-Abente 
J,Josephs DH, Spicer J, Wagner GK,  
Karagiannis SN, Chenoweth A,                    
Crescioli S, Insights from IgE immune 
surveillance in allergy and cancer for anti-
tumour IgE treatments. Cancers 2021; 
13:4460. 
Available:https://doi.org/10.3390/cancers1
3174460 

9. Di Gioacchino M, Della Valle L, Allegra A, 
Pioggia G, Gangemi S. AllergoOncology: 
role of 
immune cells and immune proteins. Clin 
Transl Allergy. 2022;e12133. 
Available:https://doi.org/10.1002/clt2.1213
3 

10. 10. Fereydouni M, Motaghed M, Ahani E, 
Kafri T, Dellinger K, Metcalfe DD, Kepley 

CL. Harnessing the Anti-Tumor Mediators 
in Mast Cells as a New Strategy for 
Adoptive Cell Transfer for Cancer. Front. 
Oncol. 2022;12:830199.  

DOI: 10.3389/fonc.2022.830199 

11. 11. Guida G, Bertolini F, Carriero V, Levra 
S, Sprio AE,  Sciolla M, Orpheu G, Arrigo E, 
Pizzimenti S, Ciprandi G, Ricciardolo FLM, 
Reliability of Total Serum IgE Levels to 
Define type 2 High and Low Asthma 
Phenotypes. J. Clin. Med. 2023;12:5447. 
Available:https://doi.org/ 
10.3390/jcm12175447 

12. Warmuzińska A, Tubek S. The Clinical 
picture of patients with the ultra-extremely 
low and extremely high total level of serum 
IgE in the material of the provincial hospital 
in opole from 2013- 2023. Clin Oncol. 
2024;9(1):2051.  

13. Ferastraoaru D, Goodman B, Rosenstreich 
D. Higher rates of malignancy in IgE 
deficient patients with negative immediate 
hypersensitivity skin tests. Ann Allergy 
Asthma Immunol. 2020  

DOI: 10.1016/j.anai.2020.10.017.  

14. Noonan E, Streasser MD, Makin T, 
Williams A, Al-Hazaymeh A, Routes JM, 
Verbsky J, Borrish L, Lawrecne MG, 
Impaired Response to Polysaccharide 
Vaccine in Selective IgE Deficiency . J Clin 
Immunol  2023 Aug;43(6):1448-1454. DOI: 
10.1007/s10875-023-01501-y. Epub 2023 
May 12. 

15. Singh N, Mott SL, Sutamtewagul G, 
McCarthy A, Slager SL, Cerhan JL, Ballas 
Z, Link BK, Prevalence and the impact of 
hypogammaglobulinemia in newly 
diagnosed chronic lymphocytic lymphoma 
patients. EJHaem 2020;1:537-44. 
Available:https://doi.org/10.1002/jha2.95 

 
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https://www.clinicsinoncology.com/open-access/the-clinical-picture-of-patients-with-the-ultra-extremely-low-and-9721.pdf
https://www.clinicsinoncology.com/open-access/the-clinical-picture-of-patients-with-the-ultra-extremely-low-and-9721.pdf
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