| 1. |
- Marcotte, Harold, et al.
(author)
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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages
- 2024
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In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 121:3
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Journal article (peer-reviewed)abstract
- The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previ- ously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot suffi- ciently boost the mucosal secretory IgA response in uninfected individuals, particu- larly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgAl antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibod- ies, dimeric and secretory IgAl antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgAl form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secre- tory IgA delivered by nasal administration may potentially be exploited for the treatment Iand prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.
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| 2. |
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| 3. |
- Abolhassani, Hassan, et al.
(author)
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X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
- 2022
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 42:1, s. 1-9
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Journal article (peer-reviewed)abstract
- Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
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| 4. |
- Borte, S., et al.
(author)
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Placental Transfer of Maternally-Derived IgA Precludes the Use of Guthrie Card Eluates as a Screening Tool for Primary Immunodeficiency Diseases
- 2012
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
-
Journal article (peer-reviewed)abstract
- There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD), 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.
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| 5. |
- Dezfouli, Mahya, et al.
(author)
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Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies
- 2020
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In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Journal article (peer-reviewed)abstract
- The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
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| 6. |
- Gunaydin, Gokce, et al.
(author)
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Mutations in Toll-Like Receptor 3 Are Associated with Elevated Levels of Rotavirus-Specific IgG Antibodies in IgA-Deficient but Not IgA-Sufficient Individuals
- 2014
-
In: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:3, s. 298-301
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Journal article (peer-reviewed)abstract
- Double-stranded RNA (dsRNA) triggers immune-mediated responses through toll-like receptor 3 (TLR3), which is involved in innate antiviral defense. Low expression of TLR3 was recently suggested to contribute to susceptibility to rotavirus infection. Thus, we investigated the role of two TLR3 polymorphisms (rs3775291 and rs5743305), both of which resulted in reduced protein function or expression, in healthy blood donors and IgA-deficient (IgAD) individuals. These polymorphisms were associated with elevated rotavirus-specific IgG titers in IgAD individuals but not in healthy individuals. Thus, we propose that TLR3 signaling does not contribute to the rotavirus-specific antibody response in IgA-sufficient individuals, whereas it is associated with elevated antibody titers in IgAD individuals.
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| 7. |
- Janzi, Magdalena, et al.
(author)
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Selective IgA deficiency in early life : Association to infections and allergic diseases during childhood
- 2009
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In: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 133:1, s. 78-85
-
Journal article (peer-reviewed)abstract
- Selective IgA deficiency in early life is quite common in Caucasian populations, but it is unclear whether it increases the risk of infections and allergic diseases during childhood. Serum IgA levels were measured in 2423 children at 4 years of age in a Swedish population based birth cohort (BAMSE). Parental questionnaires were repeatedly sent out during the child's first 8 years of life, collecting information about infections and allergic diseases. 14 children (1:173) were found to be IgA deficient at 4 years of age. These children had an increased risk of pseudocroup at year 1 (p<0.01) and food hypersensitivity at year 4 (p<0.05) as compared to IgA sufficient children. No increased risk was observed in the partial IgA deficiency group. The findings suggest that selective IgA deficiency may increase the risk of parentally reported pseudocroup and food hypersensitivity during early childhood.
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| 8. |
- Lim, Che Kang, et al.
(author)
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Reversal of Immunoglobulin. A Deficiency in Children
- 2015
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 35:1, s. 87-91
-
Journal article (peer-reviewed)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.
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| 9. |
- Sharma, Sumit, et al.
(author)
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Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades
- 2017
-
In: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 91:14
-
Journal article (peer-reviewed)abstract
- The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII. 4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII. 4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of amp;gt;= 160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P amp;lt; 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII. 4 NoV. IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII. 4 NoV. The emergence of new pandemic GII. 4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.
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| 10. |
- Wang, Ning, et al.
(author)
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Serological Assessment for Celiac Disease in IgA Deficient Adults
- 2014
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:4, s. 0093180-
-
Journal article (peer-reviewed)abstract
- Purpose: Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet. Methods: Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-even IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected. Results: Out of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti- DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not. Conclusions: IgG anti- tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.
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| 11. |
- Frankowiack, Marcel, et al.
(author)
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IgA deficiency in wolves
- 2013
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In: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 40:2, s. 180-184
-
Journal article (peer-reviewed)abstract
- Low mean concentrations of serum immunoglobulin A (IgA) and an increased frequency of overt IgA deficiency (IgAD) in certain dog breeds raises the question whether it is a breeding-enriched phenomenon or a legacy from the dog's ancestor, the gray wolf (Canis lupus). The IgA concentration in 99 serum samples from 58 free-ranging and 13 captive Scandinavian wolves, was therefore measured by capture ELISA. The concentrations were markedly lower in the wolf serum samples than in the dog controls. Potential differences in the IgA molecule between dogs and wolves were addressed by sequencing the wolf IgA heavy chain constant region encoding gene (IGHA). Complete amino acid sequence homology was found. Detection of wolf and dog IgA was ascertained by showing identity using double immunodiffusion. We suggest that the vast majority of wolves, the ancestor of the dog, are IgA deficient.
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| 12. |
- Frankowiack, Marcel, et al.
(author)
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IgA deficiency in wolves from Canada and Scandinavia
- 2015
-
In: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 50:1, s. 26-28
-
Journal article (peer-reviewed)abstract
- Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in both humans and selected breeds of domestic dogs. In both species, IgAD is associated with recurrent infections and immune mediated diseases. Previous results imply that IgAD is also common in the wild ancestor of domestic dogs, the gray wolf. Here, we report that serum IgA concentrations are significantly different in Scandinavian and Canadian wolves (p =3.252e-15) with an increased prevalence for IgAD in Scandinavian wolves (60%), which is as high as those found in high-risk dog breeds.
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| 13. |
- Gunaydin, Gokce, et al.
(author)
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Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection
- 2016
-
In: Virus Research. - : ELSEVIER SCIENCE BV. - 0168-1702 .- 1872-7492. ; 211, s. 64-68
-
Journal article (peer-reviewed)abstract
- The histo-blood group antigens (HBGAs) have recently been suggested to serve as attachment factors for rotavirus VP8* (P-genotype) in vitro and associated with susceptibility in vivo. We thus investigated whether rotavirus antibody titers and genotype specific neutralization titers correlate with HBGA status in Swedish individuals. We investigated the effect of inactivating mutations in the secretor FUT2 (rs601338) and Lewis FUT3 genes (rs28362459, rs3894326, rs812936 and rs778986) on serum IgG antibody titers and neutralizing antibody titers to rotavirus strains of the P[8] and P[6] genotypes in Swedish healthy blood donors and patients with IgA deficiency using genotyping, enzyme linked immunosorbent assay and a neutralization assay. Rotavirus-specific serum IgG and neutralizing antibody titers to the Wa strain (G1P[8]), but not to the ST3 (G4P[6]) strain, were significantly higher in secretors (with at least one functional FUT2 gene) than in non-secretors (P<0.001) (with homozygous nonsense mutation in the FUT2 gene). Thus, our results represent that secretors show elevated rotavirus specific serum antibodies, suggesting a higher susceptibility to rotavirus infections, as compared to non-secretors in Sweden. (C) 2015 Elsevier B.V. All rights reserved.
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| 14. |
- Gunaydin, Gokce, et al.
(author)
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Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus
- 2016
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- A variable fragment of a heavy chain antibody (VHH) directed against rotavirus, also referred to as anti-rotavirus protein 1 (ARP1), was shown to confer protection against rotavirus induced diarrhea in infant mouse model of rotavirus induced diarrhea. In this study, we have fused the mouse IgG1 Fc to ARP1 to improve the protective capacity of ARP1 by inducing an Fc-mediated effector function. We have shown that the Fc-ARP1 fusion protein confers significantly increased protection against rotavirus in a neonatal mouse model of rotavirus-induced diarrhea by reducing the prevalence, duration and severity of diarrhea and the viral load in the small intestines, suggesting that the Fc part of immunoglobulins may be engaged in Fc-mediated neutralization of rotavirus. Engineered conventional-like antibodies, by fusion of the Fc part of immunoglobulins to antigen-specific heavy-chain only VHH fragments, might be applied to novel antibody-based therapeutic approaches to enhance elimination of pathogens by activation of distinct effector signaling pathways.
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| 15. |
- Larsson, Per-Göran, et al.
(author)
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Extended antimicrobial treatment of bacterial vaginosis combined with human lactobacilli to find the best treatment and minimize the risk of relapses
- 2011
-
In: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 11:223
-
Journal article (peer-reviewed)abstract
- Background: The primary objective of this study was to investigate if extended antibiotic treatment against bacterial vaginosis (BV) together with adjuvant lactobacilli treatment could cure BV and, furthermore, to investigate factors that could cause relapse. less thanbrgreater than less thanbrgreater thanMethods: In all, 63 consecutive women with bacterial vaginosis diagnosed by Amsel criteria were offered a much more aggressive treatment of BV than used in normal clinical practice with repeated antibiotic treatment with clindamycin and metronidazole together with vaginal gelatine capsules containing different strains of lactobacilli both newly characterised and a commercial one (10(9) freeze-dried bacteria per capsule). Oral clindamycin treatment was also given to the patients sexual partner. less thanbrgreater than less thanbrgreater thanResults: The cure rate was 74.6% after 6 months. The patients were then followed as long as possible or until a relapse. The cure rate was 65.1% at 12 months and 55.6% after 24 months. There was no significant difference in cure rate depending on which Lactobacillus strains were given to the women or if the women were colonised by lactobacilli. The most striking factor was a new sex partner during the follow up period where the Odds Ratio of having a relapse was 9.3 (2.8-31.2) if the patients had a new sex partner during the observation period. less thanbrgreater than less thanbrgreater thanConclusions: The study shows that aggressive treatment of the patient with antibiotics combined with specific Lactobacillus strain administration and partner treatment can provide long lasting cure. A striking result of our study is that change of partner is strongly associated with relapse of BV.
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| 16. |
- Ludvigsson, Jonas F., 1969-, et al.
(author)
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Small for gestational age and risk of childhood mortality : A Swedish population study
- 2018
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In: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 15:12
-
Journal article (peer-reviewed)abstract
- Background: Small for gestational age (SGA) has been associated with increased risks of stillbirth and neonatal mortality, but data on long-term childhood mortality are scarce. Maternal antenatal care, including globally reducing the risk of SGA birth, may be key to achieving the Millennium Development Goal of reducing under-5 mortality. We therefore aimed to examine the association between SGA and mortality from 28 days to <18 years using a population-based and a sibling control design.Methods and findings: In a Swedish population study, we identified 3,795,603 non-malformed singleton live births and 2,781,464 full siblings born from January 1, 1973, to December 31, 2012. We examined the associations of severe (<3rd percentile) and moderate (3rd to <10th percentile) SGA with risks of death from 28 days to <18 years after birth. Children born SGA were first compared to non-SGA children from the population, and then to non-SGA siblings. The sibling-based analysis, by design, features a better control for unmeasured factors that are shared between siblings (e.g., socioeconomic status, lifestyle, and genetic factors). Hazard ratios (HRs) were calculated using Cox proportional hazards and flexible parametric survival models. During follow-up (1973-2013), there were 10,838 deaths in the population-based analysis and 1,572 deaths in sibling pairs with discordant SGA and mortality status. The crude mortality rate per 10,000 person-years was 5.32 in children born with severe SGA, 2.76 in children born with moderate SGA, and 1.93 in non-SGA children. Compared with non-SGA children, children born with severe SGA had an increased risk of death in both the population-based (HR = 2.58, 95% CI = 2.38-2.80) and sibling-based (HR = 2.61, 95% CI = 2.19-3.10) analyses. Similar but weaker associations were found for moderate SGA in the population-based (HR = 1.37, 95% CI = 1.28-1.47) and sibling-based (HR = 1.38, 95% CI = 1.22-1.56) analyses. The excess risk was most pronounced between 28 days and <1 year of age but remained throughout childhood. The greatest risk increase associated with severe SGA was noted for deaths due to infection and neurologic disease. Although we have, to our knowledge, the largest study sample so far addressing the research question, some subgroup analyses, especially the analysis of cause-specific mortality, had limited statistical power using the sibling-based approach.Conclusions: We found that SGA, especially severe SGA, was associated with an increased risk of childhood death beyond the neonatal period, with the highest risk estimates for death from infection and neurologic disease. The similar results obtained between the population- and sibling-based analyses argue against strong confounding by factors shared within families.
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| 17. |
- Marcotte, Harold, et al.
(author)
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Characterization and complete genome sequences of L. rhamnosus DSM 14870 and L-gasseri DSM 14869 contained in the EcoVag (R) probiotic vaginal capsules
- 2017
-
In: Microbiological Research. - : ELSEVIER GMBH, URBAN & FISCHER VERLAG. - 0944-5013 .- 1618-0623. ; 205, s. 88-98
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Journal article (peer-reviewed)abstract
- Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869 were previously isolated from the vaginal epithelial cells (VEC) of healthy women and selected for the development of the vaginal EcoVag (R) probiotic capsules. EcoVag (R) was subsequently shown to provide long-term cure and reduce relapse of bacterial vaginosis (BV) as an adjunct to antibiotic therapy. To identify genes potentially involved in probiotic activity, we performed genome sequencing and characterization of the two strains. The complete genome analysis of both strains revealed the presence of genes encoding functions related to adhesion, exopolysaccharide (EPS) biosynthesis, antimicrobial activity, and CRISPR adaptive immunity but absence of antibiotic resistance genes. Interesting features of L. rhamnosus DSM 14870 genome include the presence of the spaCBA-srtC gene encoding spaCBA pill and interruption of the gene cluster encoding long galactose-rich EPS by integrases. Unique to L. gasseri DSM 14869 genome was the presence of a gene encoding a putative (1456 amino acid) new adhesin containing two rib/alpha-like repeats. L. rhamnosus DSM 14870 and L. gasseri DSM 14869 showed acidification of the culture medium (to pH 3.8) and a strong adhesion capability to the Caco-2 cell line and VEC. L gasseri DSM 14869 could produce a thick (40 nor) EPS layer and hydrogen peroxide. L. rhamnosus DSM 14870 was shown to produce SpaCBA pili and a 20 nor EPS layer, and could inhibit the growth of Gardnerella vaginalis, a bacterium commonly associated with BV. The genome sequences provide a basis for further elucidation of the molecular basis for their probiotic functions.
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| 18. |
- Moonens, Kristof, et al.
(author)
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Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
- 2016
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In: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 19:1, s. 55-66
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Journal article (peer-reviewed)abstract
- The Helicobacter pylori adhesin BabA binds mucosal ABO/Le b blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.
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| 19. |
- Olsson, Mia, et al.
(author)
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The dog as a genetic model for immunoglobulin A (IgA) deficiency : Identification of several breeds with low serum IgA concentrations
- 2014
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In: Veterinary Immunology and Immunopathology. - : Elsevier BV. - 0165-2427 .- 1873-2534. ; 60:3-4, s. 255-259
-
Journal article (peer-reviewed)abstract
- Immunoglobulin A (IgA) serves as the basis of the secretory immune system by protecting the lining of mucosal sites from pathogens. In both humans and dogs, IgA deficiency (IgAD) is associated with recurrent infections of mucosal sites and immune-mediated diseases. Low concentrations of serum IgA have previously been reported to occur in a number of dog breeds but no generally accepted cut-off value has been established for canine IgAD. The current study represents the largest screening to date of IgA in dogs in terms of both number of dogs (n = 1267) and number of breeds studied (n = 22). Serum IgA concentrations were quantified by using capture ELISA and were found to vary widely between breeds. We also found IgA to be positively correlated with age (p < 0.0001). Apart from the two breeds previously reported as predisposed to low IgA (Shar-Pei and German shepherd), we identified six additional breeds in which > 10% of all tested dogs had very low (<0.07 g/l) IgA concentrations (Hovawart, Norwegian elkhound, Nova Scotia duck tolling retriever, Bullterrier, Golden retriever and Labrador retriever). In addition, we discovered low IgA concentrations to be significantly associated with canine atopic dermatitis (CAD, p < 0.0001) and pancreatic acinar atrophy (PAA, p = 0.04) in German shepherds.
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| 20. |
- Pant, N., et al.
(author)
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Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies
- 2007
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In: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 7
-
Journal article (peer-reviewed)abstract
- Background. Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti - rotavirus antibodies in a mouse model of rotavirus diarrhea. Results. Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. Conclusion. The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used. © 2007 Pant et al, licensee BioMed Central Ltd.
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| 21. |
- Pendharkar, Sonal, et al.
(author)
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Identification and characterisation of vaginal lactobacilli from South African women
- 2013
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In: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 13
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Journal article (peer-reviewed)abstract
- Background: Bacterial vaginosis (BV), which is highly prevalent in the African population, is one of the most common vaginal syndromes affecting women in their reproductive age placing them at increased risk for sexually transmitted diseases including infection by human immunodeficiency virus-1. The vaginal microbiota of a healthy woman is often dominated by the species belonging to the genus Lactobacillus namely L. crispatus, L. gasseri, L. jensenii and L. iners, which have been extensively studied in European populations, albeit less so in South African women. In this study, we have therefore identified the vaginal Lactobacillus species in a group of 40 African women from Soweto, a township on the outskirts of Johannesburg, South Africa. Methods: Identification was done by cultivating the lactobacilli on Rogosa agar, de Man-Rogosa-Sharpe (MRS) and Blood agar plates with 5% horse blood followed by sequencing of the 16S ribosomal DNA. BV was diagnosed on the basis of Nugent scores. Since some of the previous studies have shown that the lack of vaginal hydrogen peroxide (H2O2) producing lactobacilli is associated with bacterial vaginosis, the Lactobacillus isolates were also characterised for their production of H2O2. Results: Cultivable Lactobacillus species were identified in 19 out of 21 women without BV, in three out of five women with intermediate microbiota and in eight out of 14 women with BV. We observed that L. crispatus, L. iners, L. jensenii, L. gasseri and L. vaginalis were the predominant species. The presence of L. crispatus was associated with normal vaginal microbiota (P = 0.024). High level of H2O2 producing lactobacilli were more often isolated from women with normal microbiota than from the women with BV, although not to a statistically significant degree (P = 0.064). Conclusion: The vaginal Lactobacillus species isolated from the cohort of South African women are similar to those identified in European populations. In accordance with the other published studies, L. crispatus is related to a normal vaginal microbiota. Hydrogen peroxide production was not significantly associated to the BV status which could be attributed to the limited number of samples or to other antimicrobial factors that might be involved.
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- Smith, C. I Edvard, et al.
(author)
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Genetics of Immune Disease
- 1992
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In: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 39:3, s. 159-159
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Journal article (peer-reviewed)
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