Preferential placental transfer of <emph type=\"3\">Helicobacter pylori</emph> specific IgG

The Journal of Maternal–Fetal and Neonatal Medicine 2004;16:297–301

Case Report

Preferential placental transfer of Helicobacter pylori specific IgG M. Doroudchi 1 , 2 , A. Samsami Dehaghani 3 and A. Ghaderi 1 , 2 1

Department of Immunology, Shiraz Medical School, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran Shiraz Institute for Cancer Research, P.O. Box: 71345-3119, Shiraz, Iran 3 Department of Obstetrics and Gynecology, Medical School, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran 2

Objective: To evaluate the placental transfer of Helicobacter pylori-specific IgG in Iranian mothers. Method: The antibodies were measured in sera of 156 mother/newborn pairs using a commercially available indirect Enzyme Linked Immunosorbent Assay (ELISA). The study population was among healthy pregnant women who attended to the Zeinabieh hospital of Shiraz University of Medical Sciences in 1999. Results: In total 74.7% of mothers were seropositive and more than 82% of seropositive mothers transferred Helicobacter pylori-specific IgG antibodies to their fetuses. The mean maternal Helicobacter pylori-specific IgG was significantly higher than that of the newborns (104.01 vs. 68.30 IU/ml, p 5 0.001), however, there was a good correlation between maternal and neonatal antibodies. The level of maternal Helicobacter pylori-specific IgG was significantly lower in carriers of blood group B + compared to carriers of blood groups A + and O + . However, the cord/maternal ratio of Helicobacter pylori-specific IgG was significantly higher in blood group B + phenotype compared to blood group phenotypes A + and O + . Conclusion: The high rate of seropositivity among mothers highlights the risk of acquisition of Helicobacter pylori infection in early infancy for Iranian children. Our results also suggest that mothers having blood group B + are more likely to transfer Helicobacter pylori-specific IgG to their neonates. Key words: ABO BLOOD GROUP; HELICOBACTER; IRANIAN; PLACENTAL TRANSFER

INTRODUCTION Helicobacter pylori infection is more prevalent in developing countries and is associated with age, race, ethnicity, socioeconomic status1, household crowding2 and infection status of the family members3. The infection is mostly acquired in childhood4 and has several impacts on adult life. The bacterium itself is considered as a carcinogen for gastric cancer5 and the infection results in gastritis, duodenal ulcer, gastric ulcer6,7, gastric adenocarcinoma8 and mucosaassociated lymphoid tissue (MALT) lymphoma9. It has also been suggested that Helicobacter pylori infection may affect fetal10 and neonatal growth11, may cause iron deficiency anemia12 and failure to thrive in infancy13.

The age at acquisition of the infection in developing countries is much lower than developed countries. Reports from Peru14, Egypt15, Gambia16 and Bangladesh17 suggest a high percentage of infected children in the first year of life. This is in contrast to the low prevalence of Helicobacter pylori infected children in developed countries18,19. Although there is no comprehensive data on the seroprevalence of Helicobacter pylori in Iran, a study in pastoral nomads and industrial laborers has indicated 86.3% and 91% seropositive individuals20 which are among the highest rates reported to date21. With this high prevalence rate Iranian infants are much in risk of

Correspondence: Mehrnoosh Doroudchi, Department of Immunology, Medical School, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran # 2004 Parthenon Publishing. A member of the Taylor & Francis Group DOI: 10.1080/14767050400018148

Received 06-04-04 Revised 19-04-04 Accepted 23-04-04

Placental transfer of anti-Helicobacter IgG

acquisition of Helicobacter pylori infection very early in life. In this regard, we studied the placental transfer of Helicobacter pylori specific IgG in a group of low socioeconomic women and their newborns in Shiraz, Iran.

SUBJECTS AND METHODS Study population In total 156 pregnant women who attended to the Zeinabieh hospital of Shiraz University of Medical Sciences in 1999 were included in this study. After informed consent, 5 ml of blood was collected from mothers by venipuncture and 5 ml umbilical cord blood was collected for each infant at the time of delivery. Sera were separated from blood samples on the same day of sampling, were aliquoted in 0.5 ml volumes and stored at 7 208C until used. For 114 women demographical and clinical data were available. These data including gestational age, previous abortions, parity, mothers’ blood group and weights of newborns were recorded from patients’ files. Helicobacter pylori-specific IgG detection A commercially available indirect Enzyme Linked Immunosorbent assay (ELISA) (SERION GmbH, Germany) was used for measuring Helicobacter pylori-specific IgG in cord and maternal sera according to the manufacturer’s instructions. Sera with antibody levels 4 30 IU/ml were considered positive and sera with antibody levels 5 20 IU/ ml were considered negative. Antibody levels between 20 IU/ml and 30 IU/ml were considered as borderline value. Statistical analysis Student’s t-test for paired samples was used to compare the mean concentration of maternal and neonatal Helicobacter pylori-specific IgG. Spearman’s test was used for testing correlation of maternal and neonatal Helicobacter pylorispecific IgG. w2 test was used to evaluate the effect of different factors on seropositivity rate. ANOVA and Mann–Whitney tests were used to compare mean maternal and neonatal Helicobacter pylori-specific IgG and cord/ maternal ratios between different blood groups. Statistical analyses were performed using SPSS for Windows software version 10.0 and Microsoft Excel version 97. RESULTS The mean maternal age was 24.34 + 6.14 years; the median age of mothers was 23 years. The mean + SD of newborns’ weights was 3193 + 422 g. The main character298 Journal of Maternal–Fetal and Neonatal Medicine

Doroudchi, Dehaghani and Ghaderi

istics of studied cases and the mean Helicobacter pylorispecific IgG levels are shown in Table 1. In total, 23 (14.7%) of 156 mothers and 38 (24.4%) of 156 newborns were negative for Helicobacter-specific IgG. The number of positive cases among mothers and newborns was 116 (74.4%) and 96 (61.5%), respectively. The mean + SD of Helicobacter-specific IgG in maternal and newborn sera were 104.01 + 123.18 IU/ml and 68.30 + 75.51 IU/ml, which indicates a significantly lower level of Helicobacter pylori-specific IgG in newborn sera (p 5 0.001). There was a good correlation between maternal and fetal Helicobacter pylori-specific IgG (r = 0.82). The mean cord/maternal ratio of Helicobacter pylorispecific IgG was 0.80 + 0.57 and the median value was 0.69. Of the 156 paired samples, 118 (75.64%) had cord/ maternal ratios less than 1 and 38(24.36%) had cord/ maternal ratios greater than or equal to 1. Ten (43.48%) out of 23 blood group B + carriers, 4 (10.5%) out of 38 A +

Table 1 Characteristics of subjects and their relative Heliobacter-specific IgG No of cases Parity 1 2 3 4 5 6 7 8,9* Delivery NVD{ CS{ Unknown* Gestational age 4 37 weeks 4 37 weeks Unknown* Abortion 0 1 2 3* Total

Mean Neonatal IgG (IU/ml)

Mean Maternal IgG (IU/ml)

49 32 15 5 5 3 3 2

65.15 + 67.77 53.26 + 66.11 70.10 + 58.74 24.14 + 19.68 101.20 + 63.44 60.67 + 51.63 34.00 + 23.30 –

97.18 + 116.72 77.65 + 100.67 124.77 + 119.90 44.50 + 25.80 172.90 + 166.63 174.83 + 227.47 122.00 + 47.47 –

95 18 1

61.53 + 62.84 103.03 + 120.11 –

103.48 + 121.30 118.97 + 148.74 –

95 15 4

68.18 + 73.85 73.61 + 95.94 –

103.15 + 122.05 126.47 + 150.60 –

97 14 2 1 114

64.20 + 70.72 85.62 + 105.91 139.00 + 41.01 –

99.34 + 120.13 126.50 + 140.15 283.00 + 222.03 –

{

Normal Vaginal Delivery

{

Cesarean Section *Since there were not enough cases in these groups, data was not calculated

Placental transfer of anti-Helicobacter IgG

Table 2

Doroudchi, Dehaghani and Ghaderi

Mean + SD maternal and neonatal Helicobacter specific IgG according to mothers’ blood group

Blood group A+ B+ AB + O+ A7 B7 Total

No of cases

Mean Neonatal IgG (IU/ml)

Mean Maternal IgG (IU/ml)

64.36 + 58.60 44.19 + 50.42 103.20 + 83.39 86.33 + 99.22 20.75 + 1.77 58.16 + 47.43

38 23 5 41 2 3 112*

cord/maternal ratio

114.72 + 133.09 50.88 + 36.76 226.40 + 207.03 119.34 + 135.91 51.00 + 22.63 97.67 + 54.28

0.63 + 0.35 1.04 + 0.68 0.56 + 0.28 0.71 + 0.36 0.45 + 0.16 0.61 + 0.28

* Since there were only one case in each of the blood groups AB7 and O7, data were not included

Table 3

Seropositivity rate in different blood groups Neonatal sera

Blood group A+ B+ AB + O+ Total

No. of cases 38 23 5 41 107

Maternal sera

Positive (%)

Negative (%)

Positive (%)

24 11 3 26

9 9 1 12

28 13 4 31

(63%) (48%) (60%) (63%)

carriers and 5 (12.2%) out of 41 O + carriers had been clustered in the latter group. The mean maternal IgG in cases with cord/maternal ratios greater than or equal to 1 was 48.65 + 35.44 IU/ml, while this value in mothers with cord/maternal ratios less than 1 was 118 + 130.40 IU/ml (p = 0.01). However, there was no correlation between maternal levels of Helicobacter pylori-specific IgG and cord/ maternal ratios. Comparison of the mean maternal Helicobacter pylorispecific IgG between blood groups A + , O + and B + revealed a significant difference (p = 0.02). As shown in Table 2, a much lower level of Helicobacter pylori-specific IgG was detected in mothers having blood group B + compared to mothers having blood groups A + and O + (p = 0.05, p = 0.03). In addition, a significant difference was observed between cord/maternal ratios of Helicobacter pylori-specific IgG in carriers of these blood groups (p = 0.005). The mean cord/maternal ratio in carriers of blood group B + was 1.04 + 0.68 IU/ml while this value in owners of blood group A + and O + was 0.63 + 0.35 IU/ml and 0.56 + 0.28 IU/ml, respectively (p = 0.02, p = 0.07). In this regard, mothers having blood group B + were more likely to transfer Helicobacter pylorispecific IgG to their newborns. In addition a higher percentage of negative cases was detected in carriers of blood group B + compared to carriers of blood groups A + and O + (Table 3).

(24%) (39%) (20%) (29%)

(74%) (57%) (80%) (76%)

Negative (%) 6 (16%) 5 (22%) 0 (0%) 4 (10%)

There was no correlation between parity, type of delivery, gestational age and previous abortions with Helicobacter pylori-specific IgG in mothers and newborns. DISCUSSION In the present study we observed a high percentage (74.4%) of seropositivity among 156 studied Iranian mothers. This high percentage is consistent with the only available report from Iran20. The maternal Helicobacter pylori-specific IgG level showed a good correlation with neonatal level of this antibody. However, the mean Helicobacter pylori-specific IgG level in cord blood was significantly less than that of maternal blood, indicated by a cord/maternal ratio less than 1. By dividing the subjects into two groups, i.e. those with cord/maternal ratio 5 1 and those with cord/maternal ratio 5 1, and by considering the mean maternal IgG in these two groups, it was revealed that mothers with a lower Helicobacter pylorispecific IgG were more likely to transfer antibodies to their newborns. However, there was no correlation between maternal levels of Helicobacter pylori-specific IgG and cord/ maternal ratios. Therefore, the maternal level of Helicobacter pylori-specific IgG, per se, was not a factor influencing the transfer of these antibodies. We also observed a significant difference in the mean maternal Helicobacter pylori-specific IgG and cord/maternal 299 Journal of Maternal–Fetal and Neonatal Medicine

Placental transfer of anti-Helicobacter IgG

ratios between carriers of blood groups A + , O + and B + . In this regard, B + mothers had a significantly lower level of Helicobacter pylori-specific IgG but they were more likely to transfer these antibodies to their neonates. This was indicated by a mean cord/maternal ratio greater than 1 in this group in contrast to the mean cord/maternal ratio less than 1 in subjects having O + and A + blood groups. Therefore, it is logical to assume that the factor affecting placental transfer of Helicobacter pylori-specific antibodies is related to the maternal blood group. The lower level of maternal Helicobacter pylori-specific IgG in mothers who were carriers of B + blood group might be a consequence of lower infection rate in these individuals compared to carriers of A + and O + blood groups. As it is reported, the Helicobacter infection frequency is higher in the O and A blood group phenotype22–24. The infection rate was not investigated in our studied subjects; however, there was a higher percentage of seronegative cases in carriers of blood group B + compared to the carriers of blood group A + and O + . The intervention of the host blood group antigens with Helicobacter pylori infection and disease has been widely studied25,26. The expression of different blood group antigens, including blood group A and Lewis antigens, in the Lipopolysaccharide (LPS) of Helicobacter pylori has been reported27–29. The most important proposed role of these antigens is in the attachment and colonization of the bacterium, however, there are evidences for the role of these antigens in immune evasion and pathogenesis of the bacterium using molecular mimicry30. Our study is not the first report on the placental transfer of Helicobacter pylori-specific antibodies31,32, but to our knowledge it is the first one which highlights the effect of host ABO blood group antigens in the placental transfer of these antibodies. In the present study, 74.4% of mothers were seropositive for Helicobacter pylori-specific IgG and more than 82% of seropositive mothers transferred these antibodies to their neonates. However, 24.4% and 14.1% of the neonates were unprotected and less protected at birth, respectively. Iran is among the countries of high prevalence in which Helicobacter pylori infection is acquired very early in life. The youngest reported age of acquisition of this infection is 6 weeks33. In this regard, the risk of Helicobacter pylori infection in Iranian infants cannot be ignored. Previous reports have suggested Helicobacter pylori infection to be associated with intrauterine growth restriction10 and growth reduction in older children34,35. Iron-deficiency anemia12, malnutrition36 and protein-losing enteropathy37 are among other manifestations of this chronic infection. Acquisition of Helicobacter pylori infection in childhood may also increase the risk of developing gastric cancer later in life8,38. Helicobacter pylori infection is theoretically a preventable and eradicable infection for which the major 300 Journal of Maternal–Fetal and Neonatal Medicine

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risk factors are socioeconomic conditions and sanitation. Considering the impact of Helicobacter pylori infection on children’s growth, quality of life and adulthood diseases including gastric and esophageal cancer, it is necessary to include this bacterium in the list of health priorities in Iran.

ACKNOWLEDGEMENT This work was financially supported by Department of Immunology, Shiraz University of Medical Sciences and Shiraz Institute for Cancer Research. The study was conducted according to the current laws of the Islamic Republic of Iran.

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