Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients

AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

Genetics of inflammatory bowel disease: The role of the HLA complex

The human leucocyte antigen （HLA） complex on chromosome 6p21.3 is the most extensively studied genetic region in Inflammatory bowel disease （IBD）. Consistent evidence of linkage to IBD3 （6p21.1-23）, an area which encompasses the HLA complex, has been demonstrated for both Crohn＇s disease and ulcerative colitis, and a number of replicated associations with disease susceptibility and phenotype have recently emerged. However, despite these efforts the HLA susceptibility gene （s） for IBD remain elusive, a consequence of strong linkage disequilibrium, extensive polymorphism and high gene density across this region. This article reviews current knowledge of the role of HLA complex genes in IBD susceptibility and phenotype, and discusses the factors currently limiting the translation of this knowledge to clinical practice.

HLA-DQ:Celiac disease vs inflammatory bowel disease

AIM To determine the genetic predisposition to celiacdisease(Ce D) in inflammatory bowel disease(IBD) patients by quantifying the frequency of Ce D-related human leucocyte antigen(HLA)(HLA-Ce D: HLA-DQ2 and-DQ8) in IBD patients globally, by type of IBD and gender, and by calculating the protective/risk contribution of these haplotypes in the development of the IBD disease.METHODS We conducted a prospective study with IBD patients from our Unit. Clinical information was gathered and blood was tested for HLA-CeD. The control group was made up of unrelated Valencian organ donors.RESULTS1034 subjects were analyzed: 457 IBD [207 ulcerative coliti(UC) and 250 Crohn's disease(CD)] patients and 577 healthy controls. 39% of the controls and 34% of the patients had HLA-Ce D(P = 0.0852). HLA-DQ2 was less frequent in UC patients(P = 0.0287), and HLA-DQ8 in CD(P = 0.0217). In women with UC, the frequency of DQ2.5 cis(DQB1*02:01-DQA1*05:01) was reduced ≥ 50% [P = 0.0344; preventive fraction(PF) = 13%]. PFs(7%-14%) were obtained with all HLACe D haplotypes. HLA DQB1*02:02-DQA1*02:01(HLADQ2.2) was more frequent in CD patients with respect to controls(P = 0.001) and UC patients(etiological fraction = 15%).CONCLUSION HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and-DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development of UC, especially in women, and HLADQ8 does so for the appearance of CD. HLA-DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk factor for CD development.

Field epidemiological and experimental study on relationship between genetic factor and nonresponse or hyporesponse to hepatitis B vaccine

Objective To evaluate the role of genetic factor in the development of nonresponder or hyporesponder to hepatitis B vaccine in Chinese people from field epidemiology and experimental study Methods Six hundred and thirty four susceptible healthy students were vaccinated with three doses of plasma derived hepatitis B vaccine Twenty nine non or hypo responders (subjects) and 30 hyperresponders (controls) as well as their 80 and 79 first degree relatives were determined and recruited in the study The first degree relatives of subjects and controls were then immunized with hepatitis B vaccine and followed up On the basis of the above results, alleles of HLA A,B,C,DR and DQ locus were further detected in the two groups Results The non and hypo response rate in immunized students was 4 6% (29/634) After administered with hepatitis B vaccine, the first degree relatives of the subjects displayed a 17 9% frequency of nonresponsiveness, higher than in the controls The phenotype frequency of HLA DR7 and B54 was 52 2% and 21 7% in subjects, 9 1% and 0 0% higher than in controls, respectively The extended haplotype B54 DR7 was more frequent in the former (17 0%) than in the latter (0 0%) ( P <0 01) Conclusion These results demonstrated that the genetic factor was likely associated with the non and hypo response to hepatitis B vaccine in Chinese people

Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon

Background:Brazil has seen a great decline in malaria and the country is moving towards elimination.However,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and transmission.In this study,we aimed to evaluate whether seroprevalence to the circumsporozoite protein(CSP)is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.Methods:Cross-sectional surveys were conducted in a rural area of Porto Velho,Rondônia state.Parasite infection was detected by microscopy and polymerase chain reaction.Antibodies to the sporozoite CSP repeats of Plasmodium vivax,P.falciparum,and P.malariae(PvCS,PfCS,and PmCS)were detected using the enzyme-linked immunosorbent assay technique.Human leukocyte antigen(HLA)-DRB1 and DQB1 genes were typed using Luminex®xMAP®technology.Results:The prevalence of immunoglobulin G against P.vivax CSP peptide(62%)was higher than P.falciparum(49%)and P.malariae(46%)CSP peptide.Most of the studied individuals had antibodies to at least one of the three peptides(72%),34%had antibodies to all three peptides and 28%were non-responders.Although the majority of the population was not infected at the time of the survey,74.3%of parasite-negative individuals had antibodies to at least one of the CSPs.Importantly,among individuals carrying the haplotypes DRB1*04~DQB1*03,there was a significantly higher frequency of PfCS responders,and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders.In contrast,HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P.vivax and P.falciparum CSP repeats,and the haplotype DRB1*01~DQB1*05 was also associated with non-responders,including non-responders to P.malariae.Conclusions:Our results show that in low transmission settings,naturally acquired antibody responses against the CSP repeats of P.vivax,P.falciparum,and P.malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure,especially in an area with a high prevalence of P.vivax.Furthermore,HLA class II molecules play an important role in antibody response and require further study with a larger sample size.It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.