HLA-DRB1*0402 haplotypes without DQB1*0302 in Venezuelan patients with pemphigus vulgaris

The two basic forms of autoimmune intraepidermal blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), affect different layers of the skin, have different symptoms and target different antigens. We have defined human leukocyte antigen (HLA)-DRB1-DQB1 alleles and haplotypes in a case-control study of 66 non-Jewish patients attending a public reference Hospital over the past 10 years. The control group consisted of 101 matched individuals tested also by medium to high-resolution polymerase chain reaction-sequence-specific oligonucleotide with primers and probes from the 12th and 13th International Histocompatibility Workshop. Patients and controls were descendants of three-generation individuals born in the country. Among the patients, 49 had PV, 50% showed predominantly mucosal involvement, 50% showed predominantly the cutaneous clinical phenotype and 17 had PF. Statistically significant HLA-DR frequency differences between patients with PV and controls were found only for DRB1*0402 and DRB1*1401 [odds ratio (OR) = 27.22, confidence interval (CI) 94.7-7.82, P= 1.1 x 10(-14) and OR = 46.56, CI 801.4-2.70 P= 7.5 x 10(-6), respectively]. Both alleles were also increased in the patients with PF compared with the controls (OR = 7.0, P= 0.038 and OR = 21.64, P= 0.009, respectively), but the significance of the difference did not resist Bonferroni correction. Haplotype analysis showed that DRB1*0402 was always present with DQB1*0302 and DRB1*1401 with DQB1*0503, but no independent effect of the DQB1*0302 in the former haplotype was evident. Our results support the hypothesis that the DRB1*0402 without DQB1*0302 is the most relevant HLA-DRB1 allele responsible for the pathogenesis of pemphigus in Venezuelan patients with PV and discard the DQB1*0302 influence observed in other populations.     

Serum autoantibodies to desmogleins 1 and 3 in patients with oral lichen planus

Aim

To determine the presence of circulating autoantibodies to desmoglein (Dsg) 1 and Dsg 3 in patients with oral lichen planus.

Methods

Serum concentrations of circulating autoantibodies to Dsg 1 and Dsg 3 were determined by ELISA in 32 patients with erosive form and 25 patients with reticular form of oral lichen planus, 13 patients with acute recurrent aphthous ulcerations and 50 healthy controls. Indirect immunofluorescence analysis was also performed.

Results

Concentrations of circulating autoantibodies to both Dsg 1 and Dsg 3 detected in the sera of patients with erosive form of oral lichen planus were significantly increased in comparison with those in healthy controls, patients with recurrent aphthous ulceration, and those with reticular oral lichen planus (P<0.001 for both anti-Dsg autoantibodies). Indirect immunofluorescence also revealed significantly more positive findings in patients with erosive oral lichen planus (18 positive of 22 tested) than in healthy controls (1 positive of 20 tested; P<0.001), patients with recurrent aphthous ulceration (1 positive of 10 tested; P<0.001), and those with reticular oral lichen planus (3 positive of 15 tested; P<0.001).

Conclusion

Humoral autoimmunity seems to be involved in the pathogenesis of oral lichen planus. The differences in the serum concentration of desmoglein autoantibodies suggested that pathological mechanisms in erosive and reticular forms of oral lichen planus might not be the same.Oral lichen planus, a chronic disease and one of the most common dermatoses of the oral mucosa, is characterized by white streaks in a lace-like pattern on the tongue and/or buccal mucosa. The disease is also accompanied by chronic inflammation the degree of which correlates with the intensity of the symptoms. The disease has several forms: atrophic, erosive, reticular, and bullous, with erosive form being the predominant initial presentation (1). The etiology of oral lichen planus is still poorly understood, but the disease is considered to be autoimmune (2,3). The precipitating factors can be stress, particular food, dental plaques, systemic illness, and poor oral hygiene (2). There is substantial evidence that the pathogenesis of oral lichen planus involves a T-cell mediated process directed against basal keratinocytes (3-5), but no oral lichen planus-specific antigen has yet been identified. There is some evidence that humoral immunity may also be involved. Immunoglobulins, fibrinogen, and C3 complement may be present in the basement membrane within lesional and perilesional tissue (6), and levels of salivary IgG and IgA subclasses may also be altered (7). The presence of circulating antibodies to a lichen planus-specific antigen on the granular and deep epithelial prickle cells in the skin lesions of lichen planus was suggested (8), although the antigen itself was only infrequently demonstrated (9,10). The presence of antiepithelial antibodies was reported in patients with oral and cutaneous lichen planus associated with drug therapy, but the antibodies were generally present only in low concentrations (11). Ingafou et al (12) reported that oral lichen was not associated with IgG circulating antibodies to epithelial antigens. However, we have previously indicated the possibility of the presence of circulating antibodies to desmoglein 1 and desmoglein 3 in patients with oral lichen planus (13). Autoantibodies to desmoglein 1 and desmoglein 3, desmosomal cadherins expressed in stratified squamous epithelia and involved in cell-to-cell adhesion (14), play a pathogenic role in autoimmune bullous diseases, causing disruption of desmosoms and consequent acantholysis (15). Commercial ELISA tests for desmoglein 1 and desmoglein 3 autoantibodies are now available and have been proposed as a routine diagnostic tool (16). Although oral lichen planus and recurrent aphtohus ulceration manifest disparate clinical appearances and natural history, both of these oral mucosal diseases seem to share immunopathological features that involve T-cell mediated response to an antigenic stimulus in the epithelium (17,18).Our aim was to determine the presence of circulating autoantibodies to desmoglein 1 and desmoglein 3 in a group of patients with oral lichen planus and to compare them with healthy controls and patients with recurrent aphthous ulceration.     

HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis

The human leukocyte antigen (HLA) region has been implicated in the disease susceptibility of inflammatory bowel disease by several linkage and association studies. In Caucasians, HLA-DRB1 has been reported to determine the clinical phenotypes of ulcerative colitis (UC). Others and we previously reported that HLA-DRB1*1502 was strongly associated with UC in the Japanese population. However, the contribution of HLA-DRB1 to the clinical phenotypes in Japanese UC has not been elucidated yet. The aim of this study was to determine whether HLA-DRB1 alleles were associated with the clinical phenotypes in Japanese patients with UC. A total of 353 patients with UC were recruited. Patients were classified into subgroups by sex, age at diagnosis, disease extent, need for steroid therapy or need for surgical treatment. The allele frequency of HLA-DRB1*08 was significantly higher in patients whose disease extended beyond the rectum (left-sided and extensive UC) than in those with proctitis [odds ratio (OR)=2.20, Pc=0.043). The allele frequency of HLA-DRB1*09 was significantly higher in patients with UC diagnosed at the age of 40 years or older than in those with UC diagnosed before the age of 40 years (OR=2.31, Pc=0.022). Besides these positive associations, no significant differences were found in the allele frequencies between the other subgroups. We conclude that HLA-DRB1*09 is associated with the age at diagnosis and HLA-DRB1*08 is associated with the disease extent of UC in Japanese. These results indicate that HLA-DRB1 is not only associated with the overall UC susceptibility but also associated with the clinical phenotypes in Japanese.     

Meta-analysis of HLA-DRB1 and HLA-DQB1 polymorphisms in Latin American patients with systemic lupus erythematosus

OBJECTIVE: To estimate the common effect size of HLA-DRB1 and -DQB1 alleles on systemic lupus erythematosus (SLE) susceptibility across Latin America populations through a meta-analysis. METHODS: Case-control studies on HLA class II association with SLE in Latin America were searched up to August 2007. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model. RESULTS: Eleven studies were selected, which included 747 cases and 1180 controls. Associations with SLE susceptibility were found for HLA-DR2 (OR: 1.75; 95% CI: 1.40-2.19) and -DR3 (OR: 2.02; 95% CI: 1.44-2.83) groups. HLA-DRB1*0301 allele disclosed the strongest association (OR: 2.14; 95% CI: 1.28-3.56). HLA-DR3-DQ2 haplotype was a risk factor (OR: 2.92; 95% CI: 1.66-5.14). A protective effect was found for the HLA-DR5 group (OR: 0.43; 95% CI: 0.27-0.67), mainly due to a negative association between HLA-DRB1*1101 allele and disease (OR: 0.21; 95% CI: 0.06-0.72). Functional analysis of susceptibility and protective alleles revealed physicochemical differences of critical amino acids shaping the peptide-binding groove at DRbeta chain allowing us to infer an approach to understand the role of HLA in SLE. No significant association was established for HLA-DQB1 alleles. CONCLUSIONS: HLA-DRB1 gene is a mayor factor for development of SLE in Latin Americans.     

MICA polymorphisms and haplotypes with HLA-B and HLA-DRB1 in Koreans

Abstract
Major histocompatibility complex (MHC) class I chain-related gene A ( MICA ) is located within the human MHC, centromeric to HLA-B and telomeric to HLA-DRB1 . The location of MICA in the MHC indicates the presence of linkage disequilibrium with human leukocyte antigen (HLA). Like HLA, MICA is highly polymorphic; however, the information available for MICA polymorphisms is not as comprehensive as that for HLA polymorphisms. We estimated the allelic frequencies of MICA and haplotypes with HLA-B and HLA-DRB1 at high-resolution in a population of 139 unrelated Korean individuals by applying the newly developed method of sequence-based typing (SBT). A total of 17 MICA alleles were identified. The most frequent allele was MICA*010 (19.4%), followed by alleles *00201 (17.6%), *00801 (14.7%), *01201 (9.4%), *004 (8.3%) and *049 (7.9%). The most common two- and three-locus haplotypes were HLA-B*1501-MICA*010 (10.4%), MICA*010-HLA-DRB1*0406 (5.8%) and HLA-B*1501-MICA*010-HLA-DRB1*0406 (5.8%). This is the first study to provide such high-resolution information on the distribution of haplotypes comprising MICA , HLA-B and HLA-DRB1 in Korean individuals, a level of resolution made possible by use of the SBT method. The results of this study should help determine the mechanisms underlying diseases associated with MICA polymorphisms in Korean individuals.     

Interleukin-1beta polymorphisms in Colombian patients with autoimmune rheumatic diseases

Interleukin-1 beta (IL-1beta) exerts a range of inflammatory and immunomodulatory activities that are important in host defense and autoimmune response. The IL-1beta gene, located on chromosome 2 (2q13), is polymorphic. The influence of its polymorphism on 355 patients with autoimmune rheumatic diseases was examined. To this effect, 172 patients with rheumatoid arthritis (RA), 114 with systemic lupus erythematosus (SLE), and 69 with primary Sjogren's syndrome (pSS) were studied. The control group consisted of 392 matched healthy individuals. Genotyping of IL-1beta single-nucleotide polymorphisms (SNPs) at positions -511 (C/T) and + 3953 (C/T) was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. In addition, levels of IL-1beta were measured by immunoassay in supernatants of lipopolysaccharide (LPS)-stimulated and nonstimulated peripheral blood monocytes (PBM) obtained from 19 homozygous individuals for the three most common IL-1beta likely haplotypes, all belonging to the control group. Allele + 3953T was protective for SLE (odds ratio (OR) = 0.57, 95% confidence intervals (CI) = 0.34-0.88, P = 0.01) as was the haplotype -511C + 3953T (OR = 0.43, 95%CI = 0.25-0.74, pc = 0.006). The latter was associated with a lower LPS-stimulated-PBM IL-1beta secretion. Results suggest that IL-1beta polymorphism influences the susceptibility to acquire SLE in our population. The protective association might be explained by the observed inhibitory effect of IL-1beta + 3953T allele on the secretion of IL-1beta under inflammatory circumstances.     

HLA-DRB1 and HLA-DQB1 polymorphisms in Pacific Islands populations

Allele frequency distributions of the HLA-DRB1 and HLA-DQB1 genes were investigated in four Pacific Islands populations from the Cook Islands, Samoa, Tokelau and Tonga. Limited diversity was observed for both the HLA-DRB1 and HLA-DQB1 loci. Five HLA-DRB1 alleles were observed to be the most frequent amongst all the studied Pacific Islands populations. They were: HLA-DRB1*0403, HLA-DRB1*08032, HLA-DRB1*09012, HLA-DRB1*11011 and HLA-DRB1*1201. Cook Islanders had the largest number of low frequency DRB1 alleles followed by Samoans, Tokelauans and Tongans, most of which may be attributed to reported non-Polynesian admixture. The most frequently observed DQB1 alleles in the four studied Pacific Islands populations were those of the DQ3 subgroup of alleles HLA-DQB1*03011, HLA-DQB1*0302 and HLA-DQB1*03032 as well as HLA-DQB1*05031 and HLA-DQB1*06011. Cook Islanders had the highest number of rare HLA-DQB1 alleles, the distibution being similar to that of the HLA-DRB1 allele. While, in general, the values of homozygosity for DRB1 and DQB1 were observed to be lower then expected under neutrality, a statistical significance was observed in Tongans, Samoans and Tokelauans for the DQB1 locus and in Tongans for the DRB1 locus. Differences were observed between allele frequency distributions for Tokelauans compared to the other three populations. This was also demonstrated by principal component analysis of DRB1 and DQB1 allele frequencies, which separated the Tokelauan population from Cook Islanders, Tongans and Samoans. Tongans and Samoans were separate from the other Polynesian populations in the phylogenetic trees. Observed allele and haplotype frequencies were found to be in agreement with previously published HLA-DRB and HLA-DQB Polynesian data.     

HLA-DRB1 alleles of susceptibility and protection in Iranians with autoimmune hepatitis

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. The aim of this study was to determine the frequency of HLA-DRB1 alleles in Iranian patients with AIH and investigate the association between HLA alleles and the different types of the disease. Fifty-four AIH patients and 100 age- and sex-matched healthy controls were subjected to low resolution HLA-DRB typing performed by polymerase chain reaction-sequence-specific primers (PCR-SSP) technique. The results revealed higher frequencies of HLA-DRB1¹03, and DRB1¹13 alleles in patients with AIH compared to controls. However, DRB1¹11 was less frequent in AIH patients. In type I AIH patients HLA-DRB1¹03, HLA-DRB1¹04, HLA-DRB1¹08, and HLA-DRB1¹13 were the most frequent alleles. While in type II, the most frequent alleles were HLA-DRB1¹07 and HLA-DRB1¹13. The seronegative patients showed more frequency of HLA-DRB1¹03 and HLA-DRB3. In contrary, the frequency of HLA-DRB1¹11, HLA-DRB1¹15 and HLA-DRB5 in type 1 was less than healthy individuals. These findings indicate the role of HLA-DRB haplotypes in AIH susceptibility and protection, in the Iranian population.     

HLA-DRB1、DQB1基因与汉族人群寻常型天疱疮的相关性研究

目的　探讨 HL A- DRB1、DQB1位点基因在汉族人群寻常型天疱疮易感性中的作用。方法用序列特异性引物 -聚合酶链反应方法 ,对 6 1例寻常型天疱疮 (pemphigus vulgaris,PV)患者和 5 7名正常对照进行了 HL A- DRB1、DQB1等位基因的分型 ,并分析了 DRB1、DQB1基因在两组中的分布。结果　与正常对照组比较 ,PV组 DR4、DRB1* 14 (* 14 0 1、* 14 0 4、* 14 0 5 )基因频率明显增高 (Pc分别 <0 .0 5及P<0 .0 1) ,差异有显著性 ;PV组 DQB1* 0 5 0 3、DQB1* 0 30 2基因频率明显增高 (Pc均 <0 .0 5 ) ,差异有显著性。对 DR4阳性样本的组内基因亚型分型结果发现 ,PV组中 DRB1* 0 4 0 3、DRB1* 0 4 0 6频率显著增高(Pc<0 .0 5 ) ,差异有显著性。 PV患者组单倍型 HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3频率明显增高 (P<0 .0 5 )。结论　HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3可能是汉族人 PV推测的易感单倍型。     

Lack of association between FCRL3 and FcgammaRII polymorphisms in Japanese type 1 autoimmune hepatitis

Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA-DRB1*0405 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. Recently, polymorphisms of Fcgamma receptors (FcgammaR) and Fc receptor-like gene 3 (FCRL3) were linked to a variety of autoimmune diseases, and may be at least partially responsible for susceptibility to AIH. In this study, we genotyped FcgammaRIIA, FcgammaRIIB, and four FCRL3 polymorphisms in 87 Japanese patients with type 1 AIH and 97 ethnically matched controls using the TaqMan assay. Although we were able to detect significantly lower serum IgG concentrations in AIH patients specifically with the FCRL3-110A/A genotype, we observed no difference in the distribution of the genotypes between patients and controls, implying that susceptibility to type 1 AIH in Japanese patients is not influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms.     

HLA-DRB1 genotyping in patients with juvenile idiopathic arthritis in Taiwan.

The object of this study was to investigate whether there is an association between HLA-DRB1 alleles and the development of juvenile idiopathic arthritis (JIA) in Taiwan. HLA-DRB1 alleles were studied in 60 patients with JIA and 200 healthy controls using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probes (SSO). The frequency of HLA-DRB1*0405 in patients with JIA was found to be significantly higher than that in healthy controls [odds ratio (OR) 2.64, 95% confidence interval (CI) 1.01-6.91]. The DRB1*0405 allele was significantly associated with the development of both polyarthritis (OR 4.30, 95% CI 1.34-13.80) and oligoarthritis (OR 3.27, 95% CI 1.01-10.58). The frequency of HLA-DRB1*1502 was higher in Taiwanese JIA patients with systemic arthritis than in controls (OR 18.09, 95% CI 2.25-145.73). We conclude that, in Taiwan, HLA-DRB1*0405 is associated with the development of polyarthritis and oligoarthritis in children, and HLA-DRB1*1502 is associated with the development of systemic arthritis.     

HLA-DRB1 and DQB1 polymorphisms in southern France and genetic relationships with other Mediterranean populations

This study presents the results of HLA-DRB1 and DQB1 sequence-specific oligonucleotide probe (SSOP) typing for a population sample of 181 individuals originating from southern France. On the basis of allele and haplotype frequencies, we compared our population with others from the Mediterranean area. Allele frequencies are comparable to those found in other western European populations (France, Portugal, Spain) and indicate neighboring exchanges. The haplotype frequencies showed relationships with North Africans and Jewish populations, as well as the common origin of Moroccan and Lebanese Jews. Therefore, allele frequencies seem to be more able to show recent exchanges while haplotype frequencies might show ancestral relationships. These results may serve as references for future studies of HLA and disease in southern France.     

Molecular genetic studies of HLA-DRB1 alleles in patients with unexplained recurrent abortion in the Japanese population

BACKGROUND: Recently, evidence that HLA antigens are markers for recurrent spontaneous abortion has gained increased attention. Although the association between HLA class II antigens and patients with unexplained recurrent abortion was elucidated by a large population study in a Caucasian population, such analyses have been conducted in only a small Japanese population. The aim of the present study was to determine whether HLA-DR antigens are associated with patient populations with unexplained recurrent abortion in the Japanese population. METHODS: HLA-DRB1 genotypes were determined using a PCR-restriction fragment length polymorphism (PCR-RFLP) method in 93 patients with unexplained recurrent abortion (79 primary recurrent aborters and 14 secondary recurrent aborters) and in 115 normal fertile women. The rate of possession of each HLA-DRB1 genotype was compared among the three populations. RESULTS: The rate of possession of the HLA-DRB1*1502 in patients with secondary recurrent abortion was significantly higher (P < 0.01 after correction for multiple comparisons) compared with the control, fertile women. The rate of possession of HLA-DRB1*1502 was also higher in patients with primary recurrent abortions than in controls, but the difference was not statistically significant after correction. CONCLUSIONS: These findings suggest that HLA-DRB1*1502 might be a risk allele for unexplained recurrent abortion in the Japanese population.     

HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients

Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated.     

HLA class II antigens are associated with Japanese pemphigus patients

We investigated the HLA class II antigens in 30 Japanese cases of pemphigus, 17 cases of pemphigus vulgaris (PV) and 13 cases of pemphigus foliaceus (PF), by both serologic and restriction fragment length polymorphism (RFLP) analyses. We detected two major haplotypes susceptible to PV, i.e., DRw12-DQw7 and DRw6-DQ5. In contrast, DR2 was absent in PV. RFLP analyses showed that DRw6 PV patients had a disease-associated restriction fragment representing DQw5, the same association as that found in DRw6 Jewish PV patients. However, DRw12 Japanese PV patients had DQw7, whereas DR4 Jewish PV patients had DQw8. On the other hand, all 13 PF patients were serologically typed for DQwl, which could not be further subdivided into DQw5 by RFLP analyses. These results suggest that Japanese and Jewish PV patients may be immunogenetically closely related to each other, but Japanese PV patients appear to be immunogenetically different from Japanese PF patients. (1991).     

Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia

BACKGROUND and METHODS. We describe five patients with underlying neoplasms in whom painful mucosal ulcerations and polymorphous skin lesions developed, usually with progression to blistering eruptions on the trunk and extremities. Histologic examination showed vacuolization of epidermal basal cells, keratinocyte necrosis, and acantholysis. Immunofluorescence testing revealed atypical pemphigus-like autoantibodies in perilesional epithelium and serum from all five patients. We studied the antigenic specificities of the autoantibodies by indirect immunofluorescence and immunoprecipitation, using extracts of 14C-labeled human keratinocytes. IgG purified from the serum of one patient was passively transferred to four neonatal mice to test for pathogenicity. RESULTS. Immunofluorescence testing showed that the autoantibodies bound to the surface of tissues containing desmosomes, including complex and simple epithelia, and myocardium. An identical and unique complex of four polypeptides with molecular weights of 250, 230, 210, and 190 was immunoprecipitated by all serum samples. The 250-kd polypeptide comigrated with desmoplakin I (a protein found in the desmosomes of all epithelia), and the 230-kd antigen comigrated with the antigen of bullous pemphigoid. Cutaneous blisters, a positive Nikolsky's sign, and epidermal and esophageal acantholysis developed in all mice into which the autoantibody was injected. Electron microscopy showed epidermal acantholysis similar to lesions of experimentally induced pemphigus vulgaris. CONCLUSION. These five patients with cancer had a novel acantholytic mucocutaneous disease characterized by autoantibodies that were pathogenic after passive transfer. The autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid and two as yet unidentified epithelial antigens. We suggest the term "paraneoplastic pemphigus" for this disease.     

HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method

Abstract: We performed HLA-DQA1, -DQB1 and -DRB1 genotyping using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for 32 Japanese pemphigus vulgaris (PV) patients. There was a significant association of either DQB1*0503 or DRB1*1405 with PV, and a negative association of either DQA1*0103 or DQB1*0601 with PV was found. Since the DQB1*0503+ patients had various DR14-related alleles, we concluded that the association with DQB1 is primary and that the association with DRB1 is simply due to linkage disequilibrium between the DQ and DR genes. These results may indicate that specific HLA class II antigens confer the susceptibility to PV among Japanese.     

Cross-reactive IgM responses in patients with dengue or Japanese encephalitis.

BACKGROUND: Dengue and Japanese encephalitis viruses co-circulate in Thailand. IgM-capture enzyme-linked immunosorbent assay (ELISA) has been widely used for confirmation of dengue and Japanese encephalitis (JE). OBJECTIVES: To examine the cross-reactivity in IgM responses to dengue and JE viruses in serum and CSF samples from dengue and JE patients. STUDY DESIGN: Two hundred and fifty-eight serum samples from 177 confirmed dengue patients, and 99 serum samples and 37 cerebrospinal fluid (CSF) samples from confirmed JE patients were analyzed. RESULTS: Nine percent of serum samples from dengue patients were positive for anti-JE IgM. Thirteen percent of serum samples and 11% of CSF samples from JE patients were positive for anti-dengue IgM. Levels of cross-reactive IgM were lower than those of specific IgM in all the dengue and JE patients. CONCLUSIONS: Only specific IgM is detected in about 90% of dengue and JE patients, but cross-reactive IgM is also detected in the remainder. The presence of cross-reactive IgM responses should to be considered in the serodiagnosis of dengue and JE, especially in areas where dengue and JE viruses co-circulate.     

HLA-DRB1, DQA1 and DQB1 DNA polymorphisms in healthy Algerian and genetic relationships with other populations

Abstract: This study presents the results of HLA-DRB1, -DQA1, and -DQB1 sequence-specific oligonucleotide probe (SSOP) typings for a population sample of 47 individuals originating from Western Algeria. Allele and haplotype frequencies, as well as linkage disequilibria are computed by the standard methods used for the XIth International Histocompatibility Workshop data. A total of 24 alleles are detected at the DRB1 locus, where a very high heterozygosity level (0.914) is found. The highest DRB1 frequencies are 0.160, DRB1*1101, and 0.138, for DRB1*0301 and DRB1*0701. The DQA1 and DQB1 loci are less polymorphic. Among the 8 DQA1 alleles detected, DQA1*0501 is highly predominant with a frequency of 0.383. Thirteen DQB1 alleles are observed among which DQB1*0301 and DQB1*0201 are the most frequent (0.351 and 0.245, respectively). Three haplotypes predominate clearly: DRB1*1101-DQA1*0501-DQB1*0301 (0.138), DRB1*0701-DQA1*0201-DQB1*0201 (0.128) and DRB1*0301-DQA1*0501-DQB1*0201 (0.117). The two latter are among the most frequent haplotypes found in European and North American Caucasoid populations, but the DQA1*0501-DQB1*0201 association is not significant in Algerians. The genetic distances computed for each locus among a set of populations from different continents are significantly correlated to geography. They indicate that the Algerians are very close to South European populations, particularly to Sardinians, Italians, Romanians and French, with some intermediate characteristics between Europeans and sub-Saharan Africans. These results may serve as reference for future studies of HLA and disease in the Algerian population.