HLA-DP control of human Schistosoma haematobium infection.

Abstract

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...

Influence of Human Leukocyte Antigen Class II Alleles on Susceptibility toEntamoeba histolyticaInfection in Bangladeshi Children

“…In support of this hypothesis, several previous studies have demonstrated associations of HLA class II alleles with the susceptibility or course of infectious disease. These have included the association of the class II HLA-DRB1*1302/DQB1*0501 haplotype with mild Plasmodium falciparum malaria in The Gambia [14], class II DR*04 alleles with more-severe malaria in Gabon [15], and a controversial proposed role for a specific variable region, as opposed to an allele (position 11 of the class II DP alpha chain), in the outcome of Onchocerca volvulus and Schistosoma haematobium infections [15,16]. The HLA-DRB1*1302 allele is associated with the clearance of hepatitis B virus in The Gambia [17], and, conversely, class II DQA1*0501 and DQB1*0301 alleles are associated with persistent hepatitis B virus infection in African Americans [18].…”

Enhanced Egg-Induced Immunopathology Correlates With High IFN-γ in Murine Schistosomiasis: Identification of Two Epistatic Genetic Intervals

“…On the one hand, disease severity in infection with the three pathogenic schistosome species (S. mansoni, Schistosoma japonicum, and Schistosoma hematobium) has been linked with a variety of HLA haplotypes (14,15,17,21). On the other, a region outside the MHC on chromosome 5q31-q33, containing the SM1 gene, has been found to control disease susceptibility vs resistance in terms of intensity of infection (16,39,50); this region includes a cluster of cytokine/cytokine receptor genes that influence the outcome of immune responses against pathogens.…”

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

“…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).…”