HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection.

Meyer, Christian G.; Gallin, Michaela Y.; Erttmann, Klaus D.; Brattig, Norbert W.; Schnittger, Leonhard; Gelhaus, A.; Tannich, Egbert; Begovich, Ann B.; Erlich, Henry A.; Horstmann, Rolf D.

doi:10.1073/pnas.91.16.7515

Cited by 80 publications

(54 citation statements)

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“…8 Although the cause of differential susceptibility to clinical expression of helminth infections has only been addressed in a few human studies, early studies implicated the major histocompatibility complex (MHC). [9][10][11][12][13][14] Several large-scale studies have attempted to make more compelling the argument of an underlying genetic susceptibility for disease outcome in both filarial and schistosome infection. For example, in schistosomiasis, genetic loci for susceptibility and resistance have been physically mapped.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India

et al. 2001

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A pilot study was conducted to determine if host genetic factors influence susceptibility and outcomes in human filariasis.Using the candidate gene approach, a well-characterized population in South India was studied using common polymorphisms in six genes (CHIT1, MPO, NRAMP, CYBA, NCF2, and MBL2) . A total of 216 individuals from South India were genotyped; 67 normal (N), 63 asymptomatic microfilaria positive (MF+), 50 with chronic lymphatic dysfunction/elephantiasis (CP), and 36 tropical pulmonary eosinophilia (TPE). An association was observed between the HH variant CHIT1 genotype, which correlates with decreased activity and levels of chitotriosidase and susceptibility to filarial infection (MF+ and CP; P = 0.013). The heterozygosity of CHIT1 gene was over-represented in the normal individuals (P = 0.034). The XX genotype of the promoter region in MBL2 was associated with susceptibility to filariasis (P = 0.0093). Since analysis for MBL-sufficient vs insufficient haplotypes was not informative, it is possible the

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Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India

et al. 2001

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“…We and others have previously reported associations between DP alleles and human leukaemia (Pawelec et al, 1988;Taylor et al, 1995Taylor et al, , 2002. Furthermore, DP alleles are known to be associated with, or to act as restriction elements for a number of parasitic (Meyer et al, 1994;May et al, 1998), microbial and viral diseases, including hepatitis B and rabies (Celis and Karr, 1989;Celis et al, 1990), herpes simplex (Koelle et al, 2000), streptococcus (Dong et al, 1995), dengue virus (Kurane et al, 1993;Okamoto et al, 1998), Epstein -Barr virus (Voo et al, 2002), respiratory syncytial virus (RSV) (De Graaf et al, 2004;De Waal et al, 2004), and HIV (Cohen et al, 2006).…”

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confidence: 99%

HLA-associated susceptibility to childhood B-cell precursor ALL: definition and role of HLA-DPB1 supertypes

et al. 2008

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Childhood B-cell precursor (BCP) ALL is thought to be caused by a delayed immune response to an unidentified postnatal infection. An association between BCP ALL and HLA class II (DR, DQ, DP) alleles could provide further clues to the identity of the infection, since HLA molecules exhibit allotype-restricted binding of infection-derived antigenic peptides. We clustered 430 HLA-DPB1 alleles into six predicted peptide-binding supertypes (DP1, 2, 3, 4, 6, and 8), based on amino acid di-morphisms at positions 11 (G/L), 69 (E/K), and 84 (G/D) of the DPb 1 domain. We found that the DPb11-69-84 supertype GEG (DP2), was 70% more frequent in BCP ALL (n ¼ 687; Po10 À4 ), and 98% more frequent in cases diagnosed between 3 and 6 years (Po10 À4 ), but not o3 or 46 years, than in controls. Only one of 21 possible DPB1 supergenotypes, GEG/GKG (DP2/DP4) was significantly more frequent in BCP ALL (P ¼ 0.00004) than controls. These results suggest that susceptibility to BCP ALL is associated with the DP2 supertype, which is predicted to bind peptides with positively charged, nonpolar aromatic residues at the P4 position, and hydrophobic residues at the P1 and P6 positions. Studies of peptide binding by DP2 alleles could help to identify infection(s) carrying these peptides.

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“…27 Several other parallels of HLA associations between onchocerciasis and schistosomiasis are worth mentioning. The alleles DRB1*01, DQA1*0101, and DQB1*0501 were associated with the generalized manifestation and immunosuppression in O. volvulus infection (DRB1*01 not significant 19 ). The same alleles, which all are in strong linkage disequilibrium and constitute a particular haplotype, were also associated with weak proliferative lymphocyte responses after stimulation with soluble egg antigen induced in S. mansoni infection.…”

Section: Discussionmentioning

confidence: 99%

“…The same alleles, which all are in strong linkage disequilibrium and constitute a particular haplotype, were also associated with weak proliferative lymphocyte responses after stimulation with soluble egg antigen induced in S. mansoni infection. 11 DQB1*0201, which is associated with generalized disease in onchocerciasis, 19 is also associated with hepatosplenic S. mansoni infection. 11 The significance of MHC associations with infectious diseases is the subject of continuous controversial discussion.…”

Section: Discussionmentioning

confidence: 99%

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HLA-DP control of human Schistosoma haematobium infection.

May¹,

Kremsner²,

Milovanovic³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. The DPA1 and DPB1 alleles of the major histocompatibility complex (MHC) class II were determined in 110 patients and 120 healthy controls of a Gabonese population from an area endemic for Schistosoma haematobium infection. The MHC-DP alleles of the variable second exons and their human leukocyte antigen (HLA) epitopes were correlated with egg excretion, interleukin-4 and interferon-␥ patterns, and bladder abnormalities, as detected by ultrasonography. A methionine at position 11 of the DP␣ molecule (Met-11) and DPA1*0301 were associated with schistosomiasis when compared with controls (phenotypic gene frequencies ϭ 0.791 versus 0.583 and 0.555 versus 0.375, respectively). Met-11 homozygosity occurred more often in patients, whereas healthy controls were more frequently homozygous for an alanine at position 11 (Ala-11). The combination of the DPB1-epitope DEAV (positions 84-87 of the DP␤ molecule) and Met-11 positive DPA1 alleles was more frequent in patients than in controls (0.573 versus 0.316). Two years after antischistosomal treatment, the rate of reinfection as examined in 55 of the 110 former patients was higher in DPA1*0301-positive individuals than in those not possessing this allele (P Ͻ 0.001). Ala-11 positive individuals showed less frequently ultrasonographic signs of bladder pathology than Ala-11 negative individuals (P Ͻ 0.05). Our results suggest a role of MHC-DP elements in the manifestation of disease in S. haematobium infection.Schistosomiasis is a widespread disease in many tropical countries with substantial morbidity and mortality and enormous socioeconomic significance. Schistosoma haematobium infection leads to pathologic changes due to cellular infiltrates formed by lymphocytes, eosinophils, and macrophages, and a delayed-type hypersensitivity granulomatous inflammation around eggs deposited in the urinary tract. The severity of these pathologic changes correlates with the intensity of infection. 1 More than 10 million S. haematobium eggs in the bladder wall have been observed in autopsies. 2 Chronic damage to the urinary tract can result in obstructive uropathy, and extensive granuloma formation is often associated with progressive fibrosis and calcification. There is also some evidence that S. haematobium infection can cause squamous cancer of the bladder. 3 The diagnostic method for the classification of bladder wall abnormalities is ultrasonography. 4 Schistosoma haematobium infection is treated efficiently with praziquantel. However, reinfection after specific therapy is frequent, depending on several factors that may influence the probability and the manifestation of reinfection. 5 There is evidence for a major gene in human susceptibility and resistance to infection by the intestinal blood fluke S. mansoni, 6 and a locus controlling the intensity of that distinct infection has recently been mapped to chromosome 5q31-q33. 7 Factors of the major histocompatibility complex (MHC) have also been shown to correlate with various manifestations of schistosomiasis, mostly in studi...

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HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection.

Abstract: Human infections with the tissue nematode

Cited by 80 publications

References 31 publications

Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India

Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India

HLA-associated susceptibility to childhood B-cell precursor ALL: definition and role of HLA-DPB1 supertypes

HLA-DP control of human Schistosoma haematobium infection.

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