| 1. |
- Pushpamithran, Giggil, et al.
(författare)
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No impact of helminth coinfection in patients with smear positive tuberculosis on immunoglobulin levels using a novel method measuring Mycobacterium tuberculosis-specific antibodies
- 2023
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Ingår i: Allergy, Asthma and Clinical Immunology. - : BMC. - 1710-1484 .- 1710-1492. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.
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| 2. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 3. |
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| 4. |
- Bugaytsova, Jeanna, et al.
(författare)
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pH regulated H. pylori adherence : implications for persistent infection and disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 5. |
- Herrera, Phabiola M, et al.
(författare)
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DNA-level diversity and relatedness of Helicobacter pylori strains in shantytown families in Peru and transmission in a developing-country setting.
- 2008
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 46:12, s. 3912-3918
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Tidskriftsartikel (refereegranskat)abstract
- The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide.
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| 6. |
- Kersulyte, Dangeruta, et al.
(författare)
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Helicobacter pylori from Peruvian amerindians : traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:11, s. e15076-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.PRINCIPAL FINDINGS: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries.CONCLUSIONS: Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.
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| 7. |
- Pereira, Henrique M., et al.
(författare)
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Scenarios for Global Biodiversity in the 21st Century
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 330:6010, s. 1496-1501
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Forskningsöversikt (refereegranskat)abstract
- Quantitative scenarios are coming of age as a tool for evaluating the impact of future socioeconomic development pathways on biodiversity and ecosystem services. We analyze global terrestrial, freshwater, and marine biodiversity scenarios using a range of measures including extinctions, changes in species abundance, habitat loss, and distribution shifts, as well as comparing model projections to observations. Scenarios consistently indicate that biodiversity will continue to decline over the 21st century. However, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.
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| 8. |
- Ustun, Celalettin, et al.
(författare)
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Hematopoietic stem-cell transplantation for advanced systemic mastocytosis
- 2014
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:29, s. 3264-3274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
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| 9. |
- Åberg, Anna, et al.
(författare)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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