Jürgen F J Kun

Bells University of Technology, Abeokuta, Ogun, Nigeria

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Publications (134)517.67 Total impact

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    ABSTRACT: To characterize the genetic diversity of Plasmodium falciparum (P. falciparum) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface protein 2 (MSP-2) gene as molecular marker. Three hundred and twenty children were enrolled into the study between 2005 and 2006. These included 140 children who presented with uncomplicated malaria at the Dalhatu Araf Specialist Hospital, Lafia and another 180 children from the study area with asymptomatic infection. DNA was extracted from blood spot on filter paper and MSP-2 genes were genotyped using allele-specific nested PCR in order to analyze the genetic diversity of parasite isolates. A total of 31 and 34 distinct MSP-2 alleles were identified in the asymptomatic and uncomplicated malaria groups respectively. No difference was found between the multiplicity of infection in the asymptomatic group and that of the uncomplicated malaria group (P>0.05). However, isolates of the FC27 allele type were dominant in the asymptomatic group whereas isolates of the 3D7 allele type were dominant in the uncomplicated malaria group. This study showed a high genetic diversity of P. falciparum isolates in North-central Nigeria and is comparable to reports from similar areas with high malaria transmission intensity.
    Asian Pacific Journal of Tropical Medicine 08/2013; 6(8):589-94. · 0.50 Impact Factor
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    ABSTRACT: This study was conducted to estimate the prevalence of Plasmodium vivax and polymorphisms in the Duffy antigen receptor for chemokines (DARC) gene in patients with suspected malaria from eastern (Harar) and southwestern (Jimma) Ethiopia. Plasmodium presence and species was assessed by microscopy in 1304 and 627 febrile patients in Harar and Jimma, respectively, during October-November 2009. All microscopy-positive samples were confirmed by PCR. DARC gene polymorphisms were identified by DNA sequencing. Plasmodium vivax was the dominant species in Harar (74/98, 76%) and P. falciparum was more common in Jimma (70/107, 65%). We found 17/98 (17%) and 24/107 (22%) homozygous Duffy-negative patients in Harar and Jimma, respectively. Unexpectedly, three Duffy-negative patients from Harar had P. vivax malaria. This study documents the emergence of P. vivax malaria in Duffy-negative individuals in Ethiopia. The Duffy-negative blood group does not appear to provide absolute protection against P. vivax infection in this region.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 05/2013; 107(5):328-31. · 1.82 Impact Factor
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    ABSTRACT: A balanced proinflammatory cytokine response to Plasmodium ssp. infection is crucial to control the disease outcome. To elucidate the effect of cytokines and Plasmodium falciparum-infected erythrocytes on the regulation of interleukin (IL)-6 receptor (IL-6R), ciliary neurotrophic factor alpha (CNTFR-α) and glycoprotein (gp)130 in natural killer (NK) cells in the context of malaria, we assessed their gene expression and surface expression in NK92 cells. P. falciparum alone did not alter gene expression of the investigated receptors in NK92 cells. Analysis revealed a low effect of IL-6 on IL-6R surface expression in NK92 cells. However, at transcriptional level, a downregulation of IL-6R was observed following IL-6 stimulation. Thus, IL-6 might act within a negative feedback loop to terminate signal transduction by downregulating IL-6R expression. Additionally, we observed that IL-6R and CNTFR-α surface expression were regulated by a combination of IL-2, 12, and 18, and gp130 was influenced by interferon-α. Our results show that the IL-6 family receptors in NK92 cells are not directly influenced by P. falciparum. However, cytokines usually derived from accessory cells during malaria episodes may regulate IL-6 receptor signaling pathways. This finding encourages future studies in a more physiological context and with primary cells isolated from humans with and without malaria.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 02/2013; 33(2):65-71. · 1.63 Impact Factor
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    ABSTRACT: Due to the presence of the lake Quarun and to the particular nature of its irrigation system, it has been speculated that the Fayum, a large depression 80 kilometers south- west of modern Cairo, was exposed to the hazards of malaria in historic times. Similarly, it has been speculated that, in the same area, also human tuberculosis might have been far more widespread in the antiquity than in its recent past. If these hypotheses were confirmed, it would imply that frequent cases of co-infection between the two pathogens might have occurred in ancient populations. To substantiate those speculations, molecular analyses were carried out on sixteen mummified heads recovered from the necropolis of Abusir el Meleq (Fayum) dating from the 3(rd) Intermediate Period (1064- 656 BC) to the Roman Period (30 BC- 300 AD). Soft tissue biopsies were used for DNA extractions and PCR amplifications using well-suited protocols. A partial 196-bp fragment of Plasmodium falciparum apical membrane antigen 1 gene and a 123-bp fragment of the Mycobacterium tuberculosis complex insertion sequence IS6110 were amplified and sequenced in six and five of the sixteen specimens, respectively. A 100% concordance rates between our sequences and those of P. falciparum and M. tuberculosis complex ones were obtained. Lastly, concomitant PCR amplification of P. falciparum and M. tuberculosis complex DNA specific fragments was obtained in four mummies, three of which are (14) C dated to the Late and Graeco-Roman Periods. Our data confirm that the hydrography of Fayum was extremely conducive to the spread of malaria. They also support the notion that the agricultural boom and dense crowding occurred in this region, especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt.
    PLoS ONE 01/2013; 8(4):e60307. · 3.53 Impact Factor
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    ABSTRACT: L-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system. We investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (-986 G>A, -602 G>A, and -4 A>G in the promoter and A258S in exon 8) in 243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified) and 305 controls (135 for A258S). Patients presented lower L-ficolin plasma levels than controls (p<0.0001). Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039). Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034). We found less -4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33-0.94], P = 0.034). Heterozygote -4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5-56.8], P = 0.0001) and in indeterminate patients (OR = 3.2 [95% CI = 1.1-9.4], P = 0.037). We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1-4.5], P = 0.037). Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms. The very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism should be further evaluated in other settings.
    PLoS ONE 01/2013; 8(4):e60237. · 3.53 Impact Factor
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    ABSTRACT: Background/Purpose Malaria remains one of the most devastating parasitic diseases in the world. Its pathogenesis is still not clearly understood, although there are indications that several factors between the parasites, the host, and the environment may be involved. In malaria-endemic regions, Plasmodium falciparum infection is characterized by extensive genetic diversity. Describing this diversity provides important information about the local epidemiology of malaria and is crucial for understanding the parasite population structure and virulence, and for evaluating the impact of malaria control measures. The objective of this study was to characterize the genetic diversity of P. falciparum isolates in children with severe malaria by using polymerase chain reaction (PCR) genotyping of the highly polymorphic merozoite surface protein 2 (MSP-2) gene as a molecular marker. Methods One hundred and sixteen children who presented with symptoms of severe malaria and who had microscopically confirmed P. falciparum monoinfection were enrolled in the study after they satisfied the inclusion criteria. Parasite DNA was extracted from the blood spot on to filter paper and analyzed by genotyping the MSP-2 gene using allele-specific nested PCR. Results Twenty-six distinct MSP-2 alleles (13 FC27 alleles and 13 3D7 alleles) were detected in the study population. However, isolates of the 3D7 alleles were predominant in the population (55%), compared to isolates of the FC27 alleles (45%). However, this difference was not statistically significant. The multiplicity of infection (MOI) by P. falciparum was 1.3. Most isolates (66%) were monoclonal infections with one distinguishable clone per infected child. Conclusion The present data suggest a low complexity of P. falciparum infection in isolates of individuals with severe malaria in the study population. The data also show that most infections were monoclonal. Furthermore, no specific genotype was associated with severe malaria in this study.
    Journal of Experimental & Clinical Medicine. 01/2013; 5(4):143–147.
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    ABSTRACT: BACKGROUND: The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism. METHODS: We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections. RESULTS: We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function. CONCLUSIONS: The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.
    BMC Medical Genetics 12/2012; 13(1):117. · 2.54 Impact Factor
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    ABSTRACT: PURPOSE: Mycobacterium leprae exploits complement activation and opsonophagocytosis to infect phagocytes. M-ficolin is encoded by the FCN1 gene and initiates the lectin pathway on monocyte surfaces. We investigated FCN1 promoter polymorphisms that could be responsible for the high interindividual variability of M-ficolin levels and for modulating leprosy susceptibility. METHODS: We genotyped rs2989727 (-1981 G > A), rs28909068 (-791 G > A), rs10120023 (-542 G > A), rs17039495 (-399 G > A), rs28909976 (-271IndelT), rs10117466 (-144C > A) and rs10858293 (+33 T > G) in 400 controls and 315 leprosy patients from Southern Brazil, and in 296 Danish healthy individuals with known M-ficolin levels. RESULTS: Ten haplotypes were identified with sequence-specific PCR and/or haplotype-specific sequencing. We found evidence for a protective codominant additive effect of FCN1*-542A-144C with leprosy in Euro-Brazilians (P = 0.003, PBf = 0.021, OR = 0.243 [CI95% = 0.083-0.71]), which was independent of age, ethnic group and gender effects (P = 0.029). There was a trend for a positive association of the -399A variant in Afro-Brazilians (P = 0.022, PBf = 0.154, OR = 4.151 [CI95% = 1.115-15.454], as well as for a negative association of the FCN1*3A haplotype with lepromatous leprosy, compared with less severe forms of the disease (P = 0.016, PBf = 0.112, OR = 0.324 [CI95% = 0.123-0.858]). Danish individuals with this haplotype presented M-ficolin levels higher than the population average of circa 1,000 ng/ml, and -542A-144C, which is able to modify the recognition of transcription factors in silico, occurred in individuals with levels under the 25 percentil (P = 0.031). CONCLUSIONS: Our data provide the first evidence that FCN1 polymorphisms are associated with leprosy. M-ficolin may represent a novel key to understand the immunopathogenesis of M. leprae infection.
    Journal of Clinical Immunology 09/2012; · 3.38 Impact Factor
  • International Journal of Antimicrobial Agents 09/2012; 40(3):268-272. · 4.42 Impact Factor
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    ABSTRACT: Nasal colonisation with Staphylococcus aureus is a risk factor for invasive infection in human immunodeficiency virus (HIV)-positive individuals. This study aimed to characterise colonising S. aureus from regions with a high HIV prevalence. Single nasal swabs were taken from a total of 374 HIV-positive and 370 healthy individuals. Overall, 202 S. aureus carriers were detected. Compared with healthy individuals, HIV-positive subjects were more likely to be S. aureus nasal carriers (33% vs. 21%; P=0.0001). Isolates from HIV-positive individuals were more often resistant to meticillin (16% vs. 8%; P=0.13), chloramphenicol (47% vs. 16%; P<0.0001), sulfamethoxazole/trimethoprim (SXT) (90% vs. 55%; P<0.0001) and ciprofloxacin (18% vs. 0%; P<0.0001). Strains belonging to the spa clonal complexes 3772/ST25 and 064/ST8 were significantly more often isolated from HIV-positive individuals and exhibited greater resistance to ciprofloxacin, SXT and chloramphenicol (spa-CC 3772) or to meticillin (spa-CC 064), respectively. Panton-Valentine leukocidin gene content was high overall and was equally distributed between isolates from HIV-positive and healthy individuals (33% vs. 30%). Genotypic characteristics of colonising isolates were similar to those reported to cause invasive infection in Nigeria. The HIV pandemic contributes to the evolution of antimicrobial resistance in S. aureus. Measures to contain antimicrobial resistance of S. aureus in Nigeria must target risk groups such as HIV-positive individuals.
    International journal of antimicrobial agents 07/2012; 40(3):268-72. · 3.03 Impact Factor
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    ABSTRACT: Human ficolin-2 (L-ficolins) encoded by the FCN2 gene are pattern-recognition proteins involved in innate immunity and are associated with several infectious diseases. A Nigerian cohort of 168 Schistosoma haematobium-infected individuals and 192 healthy controls were examined for functional single-nucleotide polymorphisms in the promoter region (-986G>A, -602G>A, -4A>G) and in exon 8 (+6424G>T) using real-time polymerase chain reaction. The FCN2 -986A and -4G alleles were significantly associated with the occurrence of schistosomiasis (P = .0004 for -986G>A; P = .0001 for -4A>G). The heterozygous genotypes (P = .0006 for -986G>A; P = .0002 for -4A>G) were observed to be a risk factor for susceptibility to schistosomiasis, whereas the homozygous genotypes of major alleles (P = .0002 for -986G>A; P = .0001 for -4A>G) were observed to shield against schistosomiasis. The haplotype AGGG (P = .0002) was observed to be a risk factor for susceptibility to schistosomiasis compared with controls, and the haplotype GGAG (P = .04) was observed to confer protection compared with patients. Ficolin-2 serum level was significantly higher in controls (P < .005) and in controls with GGAG haplotypes (P < .0001). Our findings demonstrate that FCN2 promoter variants (-986G>A and -4A>G) influence ficolin-2 serum levels and susceptibility to schistosomiasis.
    The Journal of Infectious Diseases 06/2012; 206(4):562-70. · 5.85 Impact Factor
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    ABSTRACT: Cytokine-inducible SRC homology 2 domain protein (CISH) is a suppressor of cytokine signaling that controls interleukin-2 signaling pathway. We investigated the single nucleotide polymorphism (SNP) -292A>T in 473 Vietnamese hepatitis B virus (HBV) carriers and 416 healthy controls. CISH variants at -292A>T were associated to HBV infection (Allelic: OR, 1.22 95% CI, 1-1.49; P = 0.04; Recessive: OR, 1.69 95% CI 1.23-2.54; P = 0.007). A gene dose effect for the risk allele -292T was observed (P = 0.04). The level of interleukin 2 and liver enzymes such as alanine transaminase, aspartate transaminase, total bilirubin, and direct bilirubin were not associated to CISH polymorphism at position -292A>T This study associated the vital role of CISH SNP -292A>T variant to hepatitis B virus infection in a Vietnamese population.
    Immunogenetics 04/2012; 64(4):261-5. · 2.89 Impact Factor
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    ABSTRACT: Ficolin-2 coded by FCN2 gene is a soluble serum protein that plays an important role in innate immunity. In this study, we analyzed five functional polymorphisms of the FCN2 gene for their possible association with cutaneous leishmaniasis. Initially we screened 40 Syrian Arabs for the entire FCN2 gene. We investigated the contribution of FCN2 functional variants in 226 patients with cutaneous leishmaniasis and 286 healthy controls from Syria. Polymorphisms in the promoter regions (-986G/A, -602G/A, -4A/G) of the FCN2 gene were assessed by TaqMan real time PCR, whereas polymorphisms in exon8 (+6359C/T and +6424G/T) were assessed by DNA sequencing. We also measured serum ficolin-2 levels in 70 control Syrian Arabs and correlated the serum concentrations to FCN2 genotypes and haplotypes respectively. Nine new FCN2 variants including two with non synonymous substitutions in exon6 and exon8 were observed. The homozygous genotypes +6424T/T were distributed more in controls and none in patients (P = 0.04). The AGACG haplotype were observed more in patients than in controls (OR = 2.0, 95%CI 1.2-3.4, P = 0.006). The serum ficolin-2 levels were significantly distributed among the reconstructed ficolin-2 haplotypes (P<0.008) and the haplotype AGACG was observed with higher ficolin-2 levels in 70 control individuals. Our results demonstrate a significant association of FCN2 AGACG haplotype with cutaneous leishmaniasis in a Syrian Arab population. These first results provide a basis for a future study that could confirm or disprove possible relationships between FCN2 gene polymorphisms with cutaneous leishmaniasis.
    PLoS ONE 01/2012; 7(3):e34113. · 3.53 Impact Factor
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    ABSTRACT: In the early immune response to Plasmodium falciparum-infected erythrocytes (iRBC), Natural Killer (NK) cells are activated, which suggests an important role in innate anti-parasitic immunity. However, it is not well understood whether NK cells directly recognize iRBC or whether stimulation of NK cells depends mainly on activating signals from accessory cells through cell-to-cell contact or soluble factors. In the present study, we investigated the influence of membrane-bound host Heat shock protein (Hsp) 70 in triggering cytotoxicity of NK cells from malaria-naïve donors or the cell line NK92 against iRBC. Hsp70 and HLA-E membrane expression on iRBC and potential activatory NK cell receptors (NKG2C, CD94) were assessed by flow cytometry and immunoblot. Upon contact with iRBC, Granzyme B (GzmB) production and release was initiated by unstimulated and Hsp70-peptide (TKD) pre-stimulated NK cells, as determined by Western blot, RT-PCR and ELISPOT analysis. Eryptosis of iRBC was determined by Annexin V-staining. Our results suggest that presence of Hsp70 and absence of HLA-E on the membrane of iRBC prompt the infected host cells to become targets for NK cell-mediated cytotoxicity, as evidenced by impaired parasite development. Contact of iRBC with NK cells induced release of GzmB. We propose that following GzmB uptake, iRBC undergo eryptosis via a perforin-independent, GzmB-mediated mechanism. Since NK activity toward iRBC could be specifically enhanced by TKD peptide and abrogated to baseline levels by blocking Hsp70 exposure, we propose TKD as an innovative immunostimulatory agent to be tested as an adjunct to anti-parasitic treatments in vivo.
    PLoS ONE 01/2012; 7(3):e33774. · 3.53 Impact Factor
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    ABSTRACT: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria. This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed. In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008). Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children. NCT00522132.
    The Journal of Infectious Diseases 12/2011; 205(2):312-9. · 5.85 Impact Factor
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    ABSTRACT: We assessed the prevalence of Plasmodium falciparum and the frequency of the dhfr triple mutation that is associated with antifolate drug resistance among P. falciparum isolates obtained from pregnant women in Ilorin, Nigeria. The study included 179 women in the second and third trimester of pregnancy who have been exposed to intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine. Thick and thin blood films and PCR were used for malaria parasite detection. Blood group and hemoglobin concentration were also determined. Mutations in P. falciparum dhfr were analyzed by sequencing DNA obtained from blood spots on filter paper. Prevalence of P. falciparum in the population (PCR corrected) was 44.1% (79/179) with 66.7% and 33.3% in the second and third trimester, respectively. Primigravide (51.3%) were more infected than multigravide (48.7%) but the difference was not statistically significant. Women in blood group A had the highest P. falciparum malaria infection (30.8%). The mean hemoglobin concentration was lower among those infected with malaria parasite. Also, more women with the malaria parasite (38.4%) had anemia compare to those without (21.4%). The prevalence of the P. falciparum dhfr mutant alleles was 64.1%, 61.5%, 38.5%, and 12.8% for I51, R59, N108 and T108, respectively. None of the samples had the L164 mutation. The combined triple dhfr mutation (51 + 59 + 108) in the population was 17.9% (7 of 39). Also, the prevalence of the triple mutant alleles was not significantly associated to the number of doses of SP taken by the women. These findings highlight the need for a regular assessment of IPTp/SP efficacy, and evaluation of possible alternative drugs.
    Infectious disease reports 09/2011; 3(2):e16.
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    ABSTRACT: The critical barrier in control of infections remains the failure of the immune system to clear parasites despite antigen recognition. We examined and validated possible association of regulatory immune gene polymorphisms in a cohort of children with mild and severe malaria. We focussed on two precursors of the Interleukin 10 Receptor (IL10R) gene namely the IL10R alpha and IL10R beta that play a fundamental role in initiation of signal transduction. Initial screening across 40 Gabonese adult individuals revealed two promoter variants for the IL10R alpha and three for the IL10R beta precursor, respectively. Validation of these variants for their allelic gene expression by transient transfection assays exhibited an altered expression in rs56356146 and rs7925112 of the IL10R alpha (P < 0.5); rs8178435 and rs999788 in the IL10R beta constructs (P < 0.0001), respectively. We further investigated the functional role of those SNP variants exhibiting altered expression in a cohort of children with mild and severe malaria. We genotyped 145 children with mild and 185 children with severe malaria for IL10R alpha; for IL10R beta, 102 children with mild and 101 children with severe malaria. We found that none of the SNP variants had any significant association neither in children with mild or severe malaria. The haplotype -185/-116 of IL10R alpha (TT) in combination with the haplotype -754/-750 of IL10R beta (AC) contributed towards mild malaria in comparison to severe malaria [TT + AC odds ratio of 0.73 (95% CI 0.56-0.94) P = 0.01]. This study may provide a better understanding on the role of IL10R promoter allelic variants contribution to a protective effect on the development of severe malaria.
    Immunogenetics 08/2011; 64(2):87-95. · 2.89 Impact Factor
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    ABSTRACT: Lymphatic filariasis (LF) is a parasitic disease caused by threadlike worms of the Brugia and Wuchereria species that live in the human lymphatic system. Regulatory T cells (Tregs) may play a key role in the pathogenesis of LF, and cytotoxic T-lymphocyte antigen-4 (CTLA4) expressed by Tregs is a potential candidate gene because it modulates T-cell activation. A case-control study was performed to establish a potential association of 5 CTLA4 gene promoter single nucleotide polymorphisms (SNPs; rs733618, rs11571316, rs5742909, rs231775, and rs16840252) with the occurrence of LF in an East Malaysian population (320 LF-infected individuals and 150 healthy controls). Polymorphisms were evaluated using TaqMan real-time polymerase chain reaction followed by direct sequencing. LF carriers of the rs733618 AG genotypes (p = 0.02) and those with combined minor allele G carriers (AG + GG; p = 0.01) exhibited a significantly decreased risk for LF. Among the asymptomatic amicrofilaremic cases, positive associations were reported for all genotypes and variants of rs733618 with odds ratios (ORs) ranging from 0.27 to 0.45. In the asymptomatic microfilaremic cases, marker rs231775 exhibited a significant decreased risk, with ORs ranging from 0.50 to 0.57. The study has identified SNPs in the CTLA4 promoter gene that may be functionally linked with susceptibility to LF.
    Human immunology 07/2011; 72(7):607-12. · 2.55 Impact Factor
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    ABSTRACT: Deficiency of mannan-binding lectin-associated serine protease 2 (MASP-2) has been associated with infections, whereas high levels appear to increase the risk of inflammatory disorders. Nevertheless, MASP2 haplotypes have been poorly investigated. To overcome haplotyping cost and time consumption, we developed multiplex polymerase chain reactions with sequence-specific primers (PCR-SSP) for 8 single nucleotide polymorphisms (SNPs), reducing the number of necessary reactions from 18 to 7. SNPs were distributed from the promoter to the last exon, and a single PCR-SSP was used for p.D120G. We evaluated the phylogenetic relationships and global distribution of 10 identified haplotypes in 338 Danish individuals with known MASP-2 and MAp19 levels and 309 South Brazilians. Four haplotypes were associated with reduced MASP-2 levels in plasma (lower than 200 ng/mL). Simultaneous association with the highest MASP-2 (over 600 ng/mL) and lowest MAp19 levels (lower than 200 ng/mL) was demonstrated with the intron 9 mutation (Kruskal-Wallis p < 0.0001). Cumulative genotype frequencies predict approximately 0.4% severely deficient and 25% overproducing individuals in both populations. Rapid and low-cost screening of patients with multiplex MASP2 PCR-SSP could be used to identify clinical conditions where MASP-2 (or MAp19) levels may be disease modifying, possibly improving disease outcome through early therapeutic and preventive measures.
    Human immunology 06/2011; 72(9):753-60. · 2.55 Impact Factor

Publication Stats

2k Citations
517.67 Total Impact Points


  • 2013
    • Bells University of Technology
      Abeokuta, Ogun, Nigeria
  • 2011
    • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
    • Universidade Federal do Paraná
      • Departamento de Patologia Médica
      Curitiba, Estado do Parana, Brazil
    • Ladoke Akintola University of Technology
      • Department of Medical Microbiology and Pathology
      Oyo, Nigeria
  • 1998–2011
    • Medical Research Unit
      Lambaréné, Moyen-Ogooué, Gabon
    • University of Tuebingen
      • • Department of Tropical Medicine
      • • Institute for Physiology
      Tübingen, Baden-Wuerttemberg, Germany
  • 2010
    • St. George's School
      Middletown, Rhode Island, United States
  • 2009
    • Hertie-Institute for Clinical Brain Research
      Tübingen, Baden-Württemberg, Germany
  • 2008
    • The University of Manchester
      • Manchester Interdisciplinary Biocentre (MIB)
      Manchester, England, United Kingdom
  • 2007
    • Medical University of Vienna
      • Institute for Social Medicine
      Wien, Vienna, Austria
    • Inselspital, Universitätsspital Bern
      Berna, Bern, Switzerland
  • 2006
    • University of Copenhagen
      København, Capital Region, Denmark
    • Haramaya University
      Hārar, Harari Region, Ethiopia
    • Addis Ababa University
      • Department of Microbiology and Immunology
      Addis Ababa, Adis Abeba Astedader, Ethiopia
  • 2005
    • Albert Schweitzer Ziekenhuis
      Dordt, South Holland, Netherlands
  • 2003
    • St George Hospital
      Sydney, New South Wales, Australia
  • 1999
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Monash University (Australia)
      • Department of Microbiology
      Melbourne, Victoria, Australia
  • 1997
    • Royal Brisbane Hospital
      Brisbane, Queensland, Australia
  • 1995
    • Queensland Institute of Medical Research
      Brisbane, Queensland, Australia
  • 1994
    • The Walter and Eliza Hall Institute of Medical Research
      Melbourne, Victoria, Australia
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1989–1993
    • University of Cologne
      • Institute for Genetics
      Köln, North Rhine-Westphalia, Germany