Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion.

Helicobacter pylori is an important human pathogen that infects half the human population and can lead to significant clinical outcomes such as acute and chronic gastritis, duodenal ulcer, and gastric adenocarcinoma. To establish infection, H. pylori employs several mechanisms to overcome the innate and adaptive immune systems. H. pylori can modulate interleukin (IL) secretion and innate immune cell function by the action of several virulence factors such as VacA, CagA and the type IV secretion system. Additionally, H. pylori can modulate local dendritic cells (DC) negatively impacting the function of these cells, reducing the secretion of immune signaling molecules, and influencing the differentiation of CD4+ T helper cells causing a bias to Th1 type cells. Furthermore, the lipopolysaccharide (LPS) of H. pylori displays a high degree of phase variation and contains human blood group carbohydrate determinants such as the Lewis system antigens, which are proposed to be involved in molecular mimicry of the host. Lastly, the H. pylori group of outer membrane proteins such as BabA play an important role in attachment and interaction with host Lewis and other carbohydrate antigens. This review examines the various mechanisms that H. pylori utilises to evade the innate immune system as well as discussing how the structure of the H. pylori LPS plays a role in immune evasion.

Structural diversity and biological importance of ABO, H, Lewis and secretor histo-blood group carbohydrates

ABSTRACT ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.

Structural diversity and biological importance of ABO, H, Lewis and secretor histo-blood group carbohydrates.

ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.

Associations of Rhesus and non-Rhesus maternal red blood cell alloimmunization with stillbirth and preterm birth.

BACKGROUND: Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population. METHODS: All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1,022,569 singleton births from 668,952 mothers during 1987-2002. RESULTS: In total, 1.3% of the 1,022,569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births CONCLUSIONS: In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted.

Falta de associação entre o sistema Lewis e obstrução coronariana / Lack of association between the Lewis blood group system and coronary vessel obstruction

Estudos prévios demonstraram associação entre o sistema Lewis e a doença arterial coronariana (DAC) a partir da observação de que o fenótipo eritrocitário Le(a-b-) era prevalente em pacientes e propuseram que esse fenótipo representava um novo marcador de risco para essa doença. Esse estudo teve como objetivo verificar a prevalência desse marcador em pacientes brasileiros com indicação de realizar cineangiocoronariografia. A fenotipagem do sistema Lewis foi realizada pelo método gel centrifugação, e a genotipagem do loco LE foi feita pelo método PCR-RFLP. Cento e oitenta e três pacientes (114 masculinos e 69 femininos, com média de idade igual a 59,1 anos (DP ± 12,37; mediana 60) foram selecionados. Cento e vinte e um (66,1 por cento) pacientes apresentaram obstrução coronariana de qualquer grau, sendo essa característica duas vezes mais elevada no sexo masculino do que no feminino (p=0,07). As freqüências dos fenótipos eritrocitários Lewis foram semelhantes em ambos os grupos de pacientes e o fenótipo Le(a-b-) mostrou-se não estar associado à presença de obstrução coronariana (p=0,36). Elevados índices de discrepância fenótipo-genótipo foram observados entre os pacientes Le(a-b-), com base na genotipagem das mutações T59G (86,7 por cento) e T1067A (90,0 por cento). As freqüências dos alelos T e G (posição 59) e T e A (posição 1067) não mostraram diferenças estatisticamente significantes entre os pacientes com e sem obstrução coronariana (p = 0,52 e p = 0,44, respectivamente). Esses resultados demonstram que o sistema Lewis não está associado à presença de obstrução coronariana e não suportam a proposição de que o fenótipo eritrocitário Le(a-b-) representa um marcador de risco para essa doença na casuística brasileira.

Previous studies have shown an association between the Lewis blood group system and coronary artery disease (CAD) from the observation that the Le(a-b-) red blood cell phenotype was prevalent among these patients and thus proposed this red blood cell phenotype as a new genetic marker for the disease. The aim of this study was to verify the prevalence of this genetic marker among Brazilian patients who had undergone coronary arteriography. Phenotyping of the Lewis system was carried out using gel centrifugation and genotyping of the LE locus was made using PCR-RFLP. One hundred and eighty-three patients, 114 male and 69 female, with an average age of 59.1 years (SD ± 12.37; median 60), were enrolled. One hundred and twenty-one (66.1 percent) patients presented some degree of coronary obstruction, which was two times more frequent in men compared to women (p=0.07). The frequencies of the Lewis red blood cell phenotypes were similar between patients with and without coronary obstruction and the Le(a-b-) was not associated to the presence of coronary obstructions (p=0.36). A high level of discrepancies between phenotype and genotype were observed in Lewis negative patients based on genotyping of the T59G (86.7 percent) and T1067A (90.0 percent) SNPs. The frequencies of T and G alleles (position 59) and T and A alleles (position 1067) were similar among patients with and without coronary obstructions (p = 0.52 and p= 0.44, respectively). These results show that the Lewis system is not associated with the presence of coronary artery obstruction and do not support the proposition that the Le(a-b-) red blood cell phenotype represents a risk marker for this disease among Brazilian patients.