Helicobacter pylori's virulence and infection persistence define pre-eclampsia complicated by fetal growth retardation

AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. RESULTS: A significantly higher percentage of H. pyloriseropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/ CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/ VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR. CONCLUSION: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.

Helicobacter pylori infection and gastric carcinoma:Not all the strains and patients are alike

Gastric carcinoma(GC) develops in only 1%-3% of Helicobacter pylori(H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta(IL-1β) group and tumour necrosis factor-alpha(TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability(MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes(such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.

Can Helicobacter pylori infection influence human reproduction?

Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-&#x003b1;, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy

AIM： To investigate the seroprevalence of Helicobacter pylori （Hpylori） infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer （GC）. METHODS： Samples from 317 （184 males, 133 females, mean age 69±3.4 years） consecutive patientswho had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five （294 males, 261 females, mean age 57.3±4.1 years） patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic ＂gold standard＇： An enzyme immunosorbent assay was used to detect serum anti-H pylori （IgG） antibodies and Western blotting technique was utilized to search for anti-CagA protein （IgG）. RESULTS： Two hundred and sixty-one of three hundred and seventeen （82.3%） GC patients and 314/555 （56.5%） controls were seropositive for anti-H pylori （P〈0.0001; OR, 3.58; 95%CI, 2.53-5.07）. Out of the 317 cases, 267 （84.2%） were seropositive for anti-CagA antibody vs 100 out of 555 （18%） controls （P〈0.0001; OR, 24.30; 95%CI, 16.5-35.9）. There was no difference between the frequency of H pylori in intestinal type carcinoma （76.2%） and diffuse type cancer （78.8%）. Intestinal metaplasia （IM） was more frequent but not significant in the intestinal type cancer （83.4% vs 75.2% in diffuse type and 72.5% in mixed type）. Among the patients examined for IM, 39.8% had IM type Ⅰ, 8.3% type Ⅱ and 51.9% type Ⅲ （type IU vs others, P = 0.4）. CONCLUSION： This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor.

Iron Overload and Hepatitis C Virus Infection

To the Editor： We read with interest the review by Zou and Sun on the iron accumulation linked to hepatitis C virus （HCV） infection.

Protection from Preeclampsia

To the Editor：We appreciated the attentive and interesting paper by Huai et al.[1] on the protective effects of pravastatin on preeclampsia （PE）-like effects in mouse models.We would like to remind that PE is the first cause of illness and death for pregnant women and their children worldwide,the highest prevalence being in South America.Hence,every measure capable of preventing or averting the full-blown eclampsia is very welcomed.