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ORIGINAL ARTICLE
Year : 2015  |  Volume : 14  |  Issue : 4  |  Page : 177-181  

Is Helicobacter pylori infection a risk factor for idiopathic thrombocytopenic purpura in children?


1 Department of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Pediatric Hematology and Oncology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication16-Oct-2015

Correspondence Address:
Alireza Abdollahi
Department of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1596-3519.153357

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   Abstract 

Background: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder, which occurs as a result of autoantibodies attachment to the platelets surface and subsequent destruction. Several organisms can mimic features of human antigens (Ags) and induce autoantibody production. One of these organisms is Helicobacter pylori (HP). We assessed the prevalence and relationship of HP infection with ITP in a population of children. Materials and Methods: One hundred and six children younger than 18 years old were enrolled in this case-control study in which 42 children with ITP were in the case group and 64 healthy children were in the control group. Stool exam for detection of HP-Ag were performed and the variables were compared between the two groups. Results: Mean ± standard deviation age of case and control group was 6.4 ± 3.4 and 8.6 ± 4.4 years old, respectively. HP stool Ag differ significantly between the case and the control groups (P < 0.05). Conclusion: Our results support the role of HP in ITP of children, and urea breath test or Ag detection of HP in stool of these patients is recommended.

   Abstract in French 

Résumé
Contexte: Purpura thrombopénique idiopathique (PTI) est un trouble de la coagulation auto-immune, qui survient par suite de l'attachement des autoanticorps à la surface des plaquettes et la destruction subséquente. Plusieurs organismes peuvent imiter les caractéristiques des antigènes humains (Ags) et induire la production d'auto-anticorps. L'un de ces organismes est Helicobacter pylori (HP). Nous avons évalué la prévalence et la relation de l'infection à HP avec ITP dans une population d'enfants.
Matériels et méthodes: Cent six enfants âgés de moins de 18 ans vieux était inscrits dans cette étude de cas-témoins, dont 42 enfants avec PTI étaient dans le groupe et 64 enfants sains dans le groupe témoin. Examen de selles pour la détection de HP-Ag ont été réalisés et les variables ont été comparés entre les deux groupes.
Résultats: Moyenne ± écart-type âge du cas et le contrôle de groupe a été 6,4 ± 3,4 et 8,6 ± 4,4 ans, respectivement. HP tabouret Ag diffèrent sensiblement entre le boîtier et les groupes témoins (P < 0,05).
Conclusion: Nos résultats soutiennent le rôle des HP dans ITP des enfants, et le test respiratoire à l'urée ou détection de l'Ag de HP dans les selles de ces patients est recommandée.
Mots-clι s: Enfants, Helicobacter pylori, purpura thrombopénique idiopathique

Keywords: Children, Helicobacter pylori, idiopathic thrombocytopenic purpura


How to cite this article:
Abdollahi A, Shoar S, Ghasemi S, Zohreh OY. Is Helicobacter pylori infection a risk factor for idiopathic thrombocytopenic purpura in children?. Ann Afr Med 2015;14:177-81

How to cite this URL:
Abdollahi A, Shoar S, Ghasemi S, Zohreh OY. Is Helicobacter pylori infection a risk factor for idiopathic thrombocytopenic purpura in children?. Ann Afr Med [serial online] 2015 [cited 2020 Oct 19];14:177-81. Available from: https://www.annalsafrmed.org/text.asp?2015/14/4/177/153357


   Introduction Top


Helicobacter pylori (HP) is a Gram-negative bacterium discovered in 1982 and is responsible for a pandemic infection worldwide with varying prevalence in different regions more prevalent in the middle-aged adults of developing countries.[1] HP is the leading cause of many gastrointestinal diseases including peptic ulcer disease, gastritis, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma.[2],[3],[4],[5] In addition, recently it is found that HP is contributing to the pathogenesis of extra digestive disease ranging from skin disorders to atherosclerosis and autoimmune diseases such as rheumatoid arthritis, autoimmune thyroiditis, Sjoegren syndrome, Schoenlein–Henoch purpura, pernicious anemia and immune idiopathic thrombocytopenic purpura (ITP).[6],[7],[8],[9],[10],[11] It wasfirst showed by Italian researcher in 1998 that HP infection is associated with ITP and following eradication, platelets count increased in 8 patients out of 11 ones.[3],[10] In the agreement with this finding, Gasbarrini and Franceschialso reported high frequency of HP infection in ITP patients, which successfully responded to eradication treatment increasing the platelet count.[10] However, there are little evidences about such a relationship in the pediatric population. Our study hence aimed to evaluate the relationship between ITP and HP infection in Iranian children.


   Materials and Methods Top


Through a case-control study on admitted patients with diagnosed ITP in Pediatric Department of Imam Hospitals complex in Tehran, Iran, a major referral hospital in Tehran, capital of Iran, affiliated to Tehran University of Medical Sciences (TUMS), (from January to December 2013) 42 patients under the age of 18 years who fulfilled the inclusion criteria were enrolled as the case group and compared with 64 healthy age and sex matched children as the control group. The study was approved by Institutional Review Board of TUMS and informed consent was obtained from parents of children. Inclusion criteria were as follows: Platelet count <20,000/ml while other parameters of complete blood cell counts were normal, normal peripheral blood smear except decreasing amount of platelets and increased platelet size, lack of other cause of thrombocytopenia such as drugs, infections, known autoimmune diseases, malignancies, and congenital and hereditary disease. Exclusion criteria include disorders causing false positive results of stool exam for HP antigen (Ag) and treatment with antibiotics, corticosteroids therapy or bismuth and proton pomp inhibitors during the past 2 months, malignancy. The HP organism could be diagnosed by invasive methods like endoscopy, mucus biopsy of the stomach and Giemsa stain. Noninvasive methods applied to that effect include urease test and culture. Each method of diagnosis has its own advantages and disadvantages. The urease test or Ag detection are more accurate with 90–95% sensitivity and specificity. The methods of measuring Abs of HP may be less costly, but they are less accurate with 50–95% sensitivity and specificity.[11] Therefore in this study, the detection of HP-Ag in stool method is applied in the ITP children.

All patients underwent HP stool Ag testing with DRG HP-Ag (stool) ELISA (EIA-4354) Kit, DRG International, Inc., USA.

Procedure in this kit

Microplates are coated with a cocktail of affinity purified mouse monoclonal antibodies directed to the most specific HP-Ags.

In the 1st incubation, the solid phase is treated with the sample, previously extracted from stools, and simultaneously with a mixture of monoclonal antibodies to HP, conjugated with peroxidase (horseradish peroxidase).

After washing out all the other components of the sample, in the 2nd incubation the bound enzyme specifically present on the solid phase generates an optical signal that is proportional to the amount of HP-Ags present in the sample.

Calculate the mean OD 450 nm value of the standards. Then draw a calibration curve possibly using a four parameters fitting curve system. Then calculate on the curve the concentration of HP-Ag in the sample.

Ethical approval

Patients' data were considered secret, no extra cost was constrained and no intervention was performed in our study. The study design, protocols, procedures and informed consent form were approved by the Medical Ethic Committee of TUMS.

Statistical analysis

In this study, the Pearson's χ2 test and the Fisher's exact test were both employed to asses the relationship between HP infection and variables such as age, sex, and ITP. Statistical analysis was performed using SPSS 18 software (SPSS Inc., Chicago, IL, USA). Values were deemed significant when a P < 0.05 was obtained.


   Results Top


Data of 106 patients were analyzed including 42 patients (39.63%) in the case group and 64 patients (60.37%) in the control group. Mean ± standard deviation (SD) age of patients in the case group was 6.4 ± 1.4 years (range between 1.5 months and 14 years) and 8.6 ± 4.4 years in the control group (range between 6 months and 16 years). Of 38 male children, 24 ones (37.5%) were in the control group and 14 patients (33.4%) in the case group [Table 1]. On the other hands, of 68 female, 40 children (62.5%) were in the control group and 28 patients (66.6%) in the case group. HP-Ag was detected in 38 (90.47%) patient of the case group and 18 children in the control group (28.12%). In contrast, 4 patients (9.52%) in the case group and 46 children (71.87%) in the control group had negative stool exam [Table 1]. HP stool Ag differ significantly between the case and the control groups (P < 0.05).
Table 1: Demographic characteristics of children in case and control groups

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As shown in [Table 2], 13 male in the case group and 5 male in the control group and 25 female in the case group and 13 female in the control group had positive stool exam. According to [Table 3], mean ± SD age of infected patients in the case group was 14 ± 0 years and 14 ± 3.4 years old in the control group which differed significantly (P < 0.05).
Table 2: Comparison of HP stool antigen according to sex between the case and control groups

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Table 3: Comparison of age in children with positive HP stool antigen test between the case and control groups

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   Discussion Top


This study showed that children diagnosed with ITP have more HP-Ags than control group children. Moreover, the latter had a lower detection percentage of Ag in excrements than the former. Different studies are indicative of the relationship between the infection factors and an autoimmune disorder.[11],[12],[13],[14],[15],[16],[17],[18]

The HP is a Gram-negative, flagellate and microaerophilic bacterium will be colonized further in the gastric mucus.[8] Recent studies show that this organism may cause gastric ulcer or cancer, and even affect other organs like coronary arteries.[15],[16],[17],[18] Moreover, ITP is an autoimmune disease with different pathogenesis and clinical features in children and adults.[19],[20] A variety of studies have already confirmed connection between ITP and the HP infection in adults, but few studies have been conducted on children.[3],[10],[19]

Based on the current study, different hypotheses could be discussed.

Does the HP in the gastric mucus secrete inflammatory mediators like some cytokines and interleukins to affect the megakaryocytes and platelets in the blood flow or the bone marrow or the HP would damage the platelets and megakaryocytes directly? Some studies have shown that in response to some Ags, the HP produces antibodies, which would cross-react to some glycoprotein Ags of the platelets.[21],[22] It has also been proven that the HP infection and ITP trigger type-I immune response from T-helper lymphocyte cells. That would increase the level of interferon-gamma and interleukin-2.[23] They mainly confirm the hypothesis that the HP produces mediators contributing to ITP pathogen.

The relationship between the HP infection and the ITP disease wasfirst examined by Italian doctors in 1998. The studies conducted by these researchers showed that the platelets increased in 8 out of 11 ITP children after HP infection treatment.[3],[10]

Idiopathic thrombocytopenic purpura has some autoimmune features characterized with low platelet count and probably caused by autoantibodies against platelet's surface Ags.[13],[14] Some bacterial and viral infections have been introduced to evoke the autoimmune process due to the similarity with the human body Ags.[14] HP is probably a potential organism with known role in gastric and duodenal ulcers.[7],[15],[16],[17],[18],[19] We found that the prevalence of positive HP-Ag test differ between male and female, which is in the same lines with other studies. [3,7-9,22-26] Although HP is reported to be responsible in pathogenesis of ITP, Michel et al. and Figura et al. did not find any relationship between ITP and HP infection.[18],[22] Emilia et al. stated that HP was detected in 43% of ITP patients [4] and Gasbarrini and Franceschifound positive HP infection in 61% of the patients ITP patients.[10] Kohda et al.[7] reported that 62.5% of ITP patients in their study were HP positive while Sayan et al. showed that the prevalence of HP infection in ITP patients was 68.5%.[26] Based on our study results, prevalence of HP-Ag differ significantly between patients with ITP and healthy subjects. However, future studies may be conducted to investigate the potential effect of HP eradication regimen on improvement of platelet counts in pediatric ITP.

The exams for HP in children include UBT or Ag detection in stool and not measuring the level of Abs of HP in the blood because false positive and negative cases are high in the latter. Moreover, it would be difficult to differentiate an active/new infection from a chronic/old infection.

Our study population had a larger size compared to the previous study of similar types and was selected among a varying range of referees patients in our academic health care setting. A multi-center and more extensive study is recommended for the future.


   Conclusion Top


Our results support the role of HP-Ag in ITP of children. Given the endorsement of this relationship, recommended to be examined ITP-children patients for this infection. The exams are recommended to include UBT or Ag detection in stool and not measuring the level of Abs of HP in the blood because false positive and negative cases are high in the latter. Moreover, it would be difficult to differentiate an active/new infection from an infection that has happened in the past.


   Acknowledgments Top


This paper is the result of a thesis and was financially supported by Research Council of TUMS. The authors declare that there is no conflict of interests.

Source of Support:

Nil

Conflict of Interest:

None declared.

 
   References Top

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    Tables

  [Table 1], [Table 2], [Table 3]


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