Association between HLA-DQA1, HLA-DQB1 and oral cancer

Cancer is one of the most common causes of morbidity and mortality. Genes whose products play a critical role in regulation of the immune response include the HLA antigen and cytokine families of genes. Oral cancer is common in men in developing countries, and its frequency is increased by using betel-quid, tobacco, and alcohol. The association between certain HLA Class I and Class II haplotypes and cancer has been documented in a variety of tumors. There was no previous data concerning the association of specific HLA Class II DQA1, DQB1 alleles, or haplotypes with oral cancer patients. In this study, we enrolled 134 Taiwanese patients with histologically confirmed oral cancer and 268 age- and gender-matched healthy Taiwanese adults as control group to investigate the association between HLA-DQA1, HLA-DQB1 allele frequencies and oral cancer patients by using polymerase chain reaction with sequence-specific primers. We found that both HLA-DQA1* and HLA-DQB1* allele frequencies in oral cancer patients revealed no significant difference from those of control groups. Haplotype frequencies of HLA*DQA1-0103-DQB1*0601 in oral cancer patients were significantly lower than those of the control group (odds ratio: 0.18, 95% confidence interval: 0.054–0.583, p_c = 0.02). Our data suggest that HLA DQA1*0103-DQB1*0601 haplotype may be protective with regard to the development of oral cancer.     

Helicobacter pylori eradication and remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma: a long-term follow-up study

Helicobacter pylori infection plays a crucial role not only in the pathogenesis but also in the treatment of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of the present study was to evaluate whether H. pylori eradication provides a definite cure in the early stage of this neoplasia by means of a prolonged follow-up. All patients affected by low-grade gastric MALT lymphoma in stage IE that were referred to our department from January 1995 to June 1999 were enrolled in a prospective study. Diagnosis was histologically proved and H. pylori status was evaluated. Staging was performed according to a modified Ann Arbor classification. All patients who proved positive for H. pylori infection were treated with eradicating therapy, and a prolonged clinical and histologic follow-up was carried out. Until June 1999, seven low-grade gastric MALT lymphomas in stage IE were diagnosed (four men and three women; mean age, 56 years). All patients were H. pylori-positive and eradication was obtained in all of them after the first cycle of antibiotic therapy. Complete histologic regression of lymphoma was observed in all cases in a period variable between 3 and 6 months. The mean follow-up period was 42 months (range, 20-54). Only one patient showed a recurrence of lymphoma 22 months after treatment associated with H. pylori reinfection. Our results show the high efficacy of H. pylori eradication in determining a prolonged remission of low-grade gastric MALT lymphomas in stage IE. Thus, this therapeutic approach may avoid or delay the indication for more aggressive therapies, such as surgical resection.     

HLA-DRB1*15021 is the predominant allele in Japanese patients with juvenile dermatomyositis

OBJECTIVE: To investigate HLA molecules and genes in Japanese patients with juvenile dermatomyositis (JDM). METHODS: Twelve patients (8 girls and 4 boys) with ages of onset between 3 and 15 years were included. HLA class I antigen phenotypes were serologically typed by the Terasaki-NIH standard method. DNA was extracted from peripheral blood leukocytes using the phenol-chloroform extraction procedure, and stored at -70 degrees C until use. Genomic DNA for HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles in JDM patients and controls was determined by the direct sequence method. RESULTS: HLA-A24 and B52 were each detected in 7 cases (OR = 0.86, 5.02, p = 0.930, 0.006, respectively). HLA-DRB1*15021 was observed in 7 patients. This was significantly more frequent than occurred in the controls (OR = 5.72, p = 0.002). Seven patients out of 12 (58%) had the combination HLA-B52, DRB1*15021, DQA1*0103, and DQB1*0601. CONCLUSION: Our results suggest that the susceptibility gene for JDM either is HLA-DRB1*15021 or is present near the HLA-DRB1 locus. This differs from previous reports that describe the association with HLA-DQA1*0501 in Caucasian patients with JDM. The combination HLA-B52, DRB1*15021, DQA1*0103, and DQB1*0601 may contribute to the pathogenesis of JDM in Japanese patients.     

The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.

OBJECTIVES: To investigate HLA-DRB1, DQA1 and DQB1 allelic polymorphism in Iranian patients with pulmonary tuberculosis (PTB). METHODS: Forty patients with smear-positive PTB and 100 healthy individuals as a control group were studied for MHC class II allelic polymorphism by polymerase chain reaction with sequence-specific primers (PCR-SSP). The primer was supplied by biotest in the standard kit. DRB low resolution SSP and DQA, DQB intermediate resolution SSP was applied. RESULTS: The comparison of the patients and the control group showed a significant increase in the frequency of the HLA-DRB1*07 and DQA1*0101 alleles (OR 2.7, 95%CI 1.19-6.13, P = 0.025 and OR 2.66, 95%CI 1.15-6.44, P = 0.04, respectively) in the patient group. The frequency of DQA1*0301 and DQA1*0501 was also significantly decreased (OR 0.254, 95%CI 0.075-0.865, P = 0.033 and OR 0.53, 95%CI 0.3-0.95, P = 0.045, respectively) in the PTB patients. Concerning haplotype frequency, DRB1*11501, QDQA1*0103 and DQB1*0601 were increased, but this difference was not statistically significant. In the DQB1 locus, DQB1*0501 was non-significantly over-represented. CONCLUSIONS: HLA-DRB1*07 and HLA-DQA1*0101 appeared to be the predisposing alleles and HLA-DQA1*0301 and 0501 the protective alleles in our patients with TB.     

Ⅱ类人白细胞抗原等位基因与晚期肝脾型日本血吸虫病的相关性研究

目的　探讨Ⅱ类人白细胞抗原 (HLA-Ⅱ)基因多态性与晚期肝脾型日本血吸虫病的相关性。　方法　用聚合酶链反应-序列特异性引物 (PCR-SSP)技术对 46例晚期肝脾型日本血吸虫病患者 (实验组 )和 43例慢性日本血吸虫病患者 (对照组 )HLA-DRB1、DPA1、DQA1和DQB14个基因位点的等位基因进行分型。对两组间等位基因频率的差异进行 χ² 检验。　结果　实验组HLA-DRB1*04、DPA1*0103、DQA1*0601和DQB1*020 1等位基因频率明显高于对照组 ,而HLA-DQA1*0501和DQB1*0601等位基因频率明显低于对照组。　结论　HLA-DRB1*04、DPA1*0103、DQA1*0601和DQB1*0201等位基因 ,因其与晚期肝脾型日本血吸虫病呈显著的正相关 (P <0.0 5 )而可能是该病的遗传易感基因 ,而HLA-DQA1*0501和DQB1*0601等位基因与对该病存在抵抗性有关。     

Association of HLA-DQA1*0101/2 and DQB1*0502 with Myasthenia Gravis in Southern Iranian Patients

Background: Myasthenia gravis is an autoimmune disorder of neuromuscular junction characterized by skeletal muscle weakness and fatigability. Different genes may control the induction and clinical presentation of this disease. Various HLA alleles are reported as predisposing or protective genetic elements in myasthenia gravis. Objective: The aim of this study was to investigate the probable association between HLA-DQ alleles and myasthenia gravis in southern Iranian patients. Methods: HLA-DQA1 and DQB1 alleles were determined in 104 sporadic patients with myasthenia gravis using polymerase chain reaction - restriction fragment length polymorphism method and the results were compared to 816 healthy controls. Results: HLA-DQA1*0101/2 (39.4%) and DQB1*0502 (21.6%) were the most frequent alleles in southern Iranian patients with myasthenia gravis. These alleles revealed positive associations with the disease with relative risks of 1.69 and 2.41, respectively. The most common haplotype was DQA1*0101/2-DQB1*0502 in these patients. Conclusion: According to the results of this study, DQA1*0101/2 and DQB1*0502 alleles might be considered as predisposing genetic factors to myasthenia gravis while DQA1*0501, DQB1*0301 and *0602/3 show protective roles against this disease.     

Halitosis in patients with Helicobacter pylori-positive non-ulcer dyspepsia: an indication for eradication therapy?

BACKGROUND: The aims of this study were to investigate the frequency of halitosis before and after eradication therapy and to determine whether halitosis is a valid indication for eradication therapy in patients with Helicobacter pylori (H. pylori)-positive non-ulcer dyspepsia. METHODS: Dyspepsia, related symptoms, and halitosis were investigated by way of a questionnaire. Only H. pylori-positive patients who showed no organic lesions on endoscopic examination and no atrophy histopathologically were included. A total of 148 patients fulfilled the above criteria and completed the study. Four weeks after the end of eradication treatment, the symptoms were re-evaluated and repeat endoscopy was done to check for H. pylori in the gastric mucosa. Results: H. pylori eradication was successful in 109 patients (73.6%). Prior to treatment, bloating was the most frequent symptom (74.3%), followed by diurnal pain (62.2%) and halitosis (61.5%). The most successfully resolved symptoms in the group as a whole, regardless of eradication status, were halitosis, diurnal pain, and hunger-like pain, respectively. In the patients with confirmed H. pylori eradication, the most successfully resolved symptoms were halitosis and hunger-like pain, respectively. CONCLUSION: Halitosis is a frequent, but treatable, symptom of H. pylori-positive non-ulcer dyspepsia and may be a valid indication for eradication therapy.     

DR- and DQ-associated protection from type 1A diabetes: comparison of DRB1*1401 and DQA1*0102-DQB1*0602*

The transmission disequilibrium test was used to analyze haplotypes for association and linkage to diabetes within families from the Human Biological Data Interchange type 1 diabetes repository (n = 1371 subjects) and from the Norwegian Type 1 Diabetes Simplex Families study (n = 2441 subjects). DQA1*0102-DQB1*0602 was transmitted to 2 of 313 (0.6%) affected offspring (P < 0.001, vs. the expected 50% transmission). Protection was associated with the DQ alleles rather than DRB1*1501 in linkage disequilibrium with DQA1*0102-DQB1*0602: rare DRB1*1501 haplotypes without DQA1*0102-DQB1*0602 were transmitted to 5 of 11 affected offspring, whereas DQA1*0102-DQB1*0602 was transmitted to 2 of 313 affected offspring (P < 0.0001). Rare DQA1*0102-DQB1*0602 haplotypes without DRB1*1501 were never transmitted to affected offspring (n = 6). The DQA1*0101-DQB1*0503 haplotype was transmitted to 2 of 42 (4.8%) affected offspring (P < 0.001, vs. 50% expected transmission). Although DRB1*1401 is in linkage disequilibrium with DQB1*0503, neither of the two affected children who carried DQA1*0101-DQB1*0503 had DRB1*1401. However, all 13 nonaffected children who inherited DQA1*0101-DQB1*0503 had DRB1*1401. In a case-control comparison of patients from the Barbara Davis Center, DQA1*0101-DQB1*0503 was found in 5 of 110 (4.5%) controls compared with 3 of 728 (0.4%) patients (P < 0.005). Of the three patients with DQB1*0503, only one had DRB1*1401. Our data suggest that both DR and DQ molecules (the DRB1*1401 and DQA1*0102-DQB1*0602 alleles) can provide protection from type 1A diabetes.     

The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population

Background and Aim:  To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C.
Methods:  A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction–sequencing based typing (PCR-SBT).
Results:  Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse.
Conclusions:  These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.     

Seroprevalence of eight Helicobacter pylori antigens among 182 patients with peptic ulcer, MALT gastric lymphoma or non-ulcer dyspepsia. Higher rate of seroreactivity against CagA and 35-kDa antigens in patients with peptic ulcer originating from Europe and Africa.

BACKGROUND: It has been suggested that Helicobacter pylori may induce more or less severe gastroduodenal disease according to the strain virulence. DESIGN: We used Western blot to determine antigenic profiles associated with duodenal or gastric ulcer disease, MALT lymphoma and non-ulcer dyspepsia, and to identify geographical differences. METHODS: One hundred and eighty-two consecutive patients with H. pylori infection were studied. H. pylori infection was diagnosed by a rapid urease test or histological examination of gastric biopsy samples. Bacterial density and gastritis were assessed histologically by using the Sydney scoring system. Western blot was used to identify antibodies against eight antigens (CagA, VacA, urease A, heat shock protein B, and 19.5, 26.5, 30 and 35 kDa). Patients were questioned on their smoking habits and place of birth and childhood. RESULTS: There were 73 patients with duodenal ulcer, 30 with gastric ulcer, eight with erosive duodenitis, 17 with gastric MALT lymphoma and 54 with non-ulcer dyspepsia. Most (>85%) were seropositive for the heat shock protein B and 26.5-kDa antigens. The prevalence of the other antigens ranged from 45% (VacA) to 68% (urease B). The seroprevalence of CagA antigen was significantly higher (P < 0.01) in cases of gastroduodenal ulcer (84%) than non-ulcer dyspepsia (37%). Similarly, 35-kDa antigen reactivity was more frequent (P < 0.05) in duodenal ulcer patients (75%) than in those with non-ulcer dyspepsia (50%). The antigenic profiles associated with MALT gastric lymphoma and non-ulcer dyspepsia were similar. Multivariate analysis showed that only gastroduodenal ulcer was significantly associated with CagA. Gastroduodenal ulcer and a childhood spent in Africa were both associated with 35-kDa and combined CagA-35-kDa reactivity. CONCLUSIONS: This study confirms the strong seroprevalence of H. pylori CagA antigen and shows a high prevalence of the 35-kDa antigen in patients with gastroduodenal ulcer, especially those raised in Africa. There was no difference in the serological pattern between patients with non-ulcer dyspepsia and those with MALT lymphoma. Tests for antibodies to the CagA-35-kDa antigen combination might be used to select H. pylori-infected dyspeptic patients warranting treatment.     

Ciprofloxacin-omeprazole combination therapy for eradication of Helicobacter pylori

20 H. pylori-positive patients with gastric or duodenal ulcer disease (n = 16, one with proof of gastric cancer obtained by histology) or severe non-ulcer dyspepsia (n = 4) were entered in a pilot study to examine the effect of a combination of omeprazole (40 mg) before breakfast and ciprofloxacin (2 x 500 mg) 1 hour after meals for 1 week to treat Helicobacter pylori (Hp). The eradication rate was 15% (3 out of 20 patients) 4 weeks after therapy. Ulcer healing occurred in 2 of 3 patients having eradication and 9 of 11 control patients with positive H. pylori urease test and/or culture 4 weeks after treatment. Despite some good theoretical background, this drug combination is inefficient to eradicate H. pylori and cannot be recommended for routine clinical practice. No major side effects of the therapy-regimen were observed.     

Insulin autoantibodies and high titre islet cell antibodies are preferentially associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical onset of Type 1 (insulin-dependent) diabetes mellitus before age 10 years,but not at onset between age 10 and 40 years

Summary Demographic and biological data were collected from all Caucasian Type 1 diabetic patients (n = 279) who were recruited at clinical onset by the Belgian Diabetes Registry over 34 months. The male/female ratio was significantly higher for onset between age 20 and 40 years (2.4) than before age 20 years (1.0); no age-or sex-differences were noticed in serum fructosamine concentration. Total and high concentrations of insulin autoantibodies and islet cell antibodies were preferentially associated with the HLA DQA1*0301-DQB1*0302 susceptibility haplotype. The occurrence of both types of antibodies was also correlated, irrespective of haplotype. At onset before age 10 years, the high risk genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 was more prevalent than all other DQA1-DQB1 genotypes taken together, leading to a higher prevalence of the DQA1*0301-DQB1*0302 haplotype in this age group (75%) than in the 10–39 years age group (54%). Under age 10 years, the presence of DQA1*0301-DQB1*0302 was strongly associated with insulin autoantibodies (90%) and islet cell autoantibodies (92% with 85% of high titre), whereas patients without this haplotype were less frequently positive for insulin autoantibodies (31%) or islet cell autoantibodies (38% high titre). In the group with onset at age 10–39 years, the DQA1*0301-DQB1*0302 haplotype presented a lower association with insulin autoantibodies (40%) and islet cell autoantibodies (50 to 65% high titre), prevalences which no longer differed from those in subjects lacking this haplotype. The present data demonstrate that variations in prevalence of insulin autoantibodies and islet cell autoantibodies at onset of Type 1 diabetes can result from differences in age and in the fraction of patients with the HLA DQA1*0301-DQB1*0302 haplotype. The presence of this susceptibility haplotype at onset under age 10 years identifies a sub-group of patients with more than 90% positivity for insulin autoantibodies and more than 90% positivity for islet cell autoantibodies. It is conceivable that this sub-group can be recognized in the pre-diabetic phase through screening for immunological and genetic markers.     

Are twelve days of omeprazole, amoxicillin and clarithromycin better than six days for treating H. pylori infection in peptic ulcer and in non-ulcer dyspepsia?

BACKGROUND/AIMS: To evaluate whether omeprazole, amoxicillin and clarithromycin for 12 days is more effective for Helicobacter pylori eradication than the same regimen for only 6 days; and to verify whether these eradication regimens are more effective in peptic ulcer disease than in non-ulcer dyspepsia. METHODOLOGY: We studied 411 patients in whom a gastroscopy was carried out due to symptoms related to the upper gastrointestinal tract and who were diagnosed with duodenal ulcer (175 patients, 43%), gastric ulcer (42 patients, 10%), or non-ulcer dyspepsia (194 patients, 47%), and concomitant infection by H. pylori. At endoscopy, biopsies were obtained for rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated four weeks after completing eradication treatment with 1) omeprazole (20 mg b.i.d.), amoxicillin (1 g b.i.d.) and clarithromycin (500 mg b.i.d.) for six days (239 patients), or 2) the same regimen for 12 days (172 patients). RESULTS: H. pylori eradication was achieved in 73.6% (95% CI, 68-79%) of the patients treated during 6 days, and in 84.3% (79-90%) of those receiving 12 days of therapy (P < 0.01). The overall eradication rate with both regimens (6 plus 12 days), respectively in patients with duodenal ulcer, gastric ulcer and non-ulcer dyspepsia, was 84.6% (79-90%), 75.6% (61-86%), and 72.8% (67-79%) (P < 0.01 when comparing duodenal ulcer vs. non-ulcer dyspepsia). Twelve-day regimen was more effective than 6-day regimen only in non-ulcer dyspepsia (62% vs. 83%, P < 0.01), but not in duodenal or gastric ulcer. In the multivariate analysis the duration (6 vs. 12 days) of eradication therapy (odds ratio: 2.2; 1.3-3.7) and the type of disease (duodenal ulcer vs. non-ulcer dyspepsia; odds ratio: 2.3; 1.3-3.8) were the only variables which influenced on H. pylori eradication efficacy (chi 2 model, 17; P < 0.001). CONCLUSIONS: Efficacy with omeprazole-amoxicillin-clarithromycin regimen in patients with duodenal ulcer is higher than in those patients with non-ulcer dyspepsia. The increase of H. pylori eradication rate by 21% in our non-ulcer dyspepsia patients justifies the prolongation from 6 to 12 days of omeprazole-amoxicillin-clarithromycin therapy, whilst the increase of cure rates in duodenal or gastric ulcer patients with a 12-day therapy would not be cost-effective.     

Treatment of Helicobacter pylori infection

It has been 2 decades since the rediscovery of Helicobacter pylori. Since that time, enormous advances have occurred: H. pylori is clearly felt to be a cause of peptic ulcer disease and gastric malignancies such as mucosa associated lymphoid tissue (MALT) lymphoma and a carcinogenic factor for gastric adenocarcinoma. These associations have led to clear indications for H. pylori treatment in certain conditions, but in other diseases where the associations are not as clear, the indications also remain relatively controversial. Clear indications for H. pylori treatment include patients with duodenal and gastric H. pylori associated ulcers and MALT lymphoma. In uninvestigated dyspepsia, there are also very clear benefits to H. pylori treatment whereas in non-ulcer dyspepsia, the benefits are controversial. H. pylori is certainly a risk factor for gastric adenocarcinoma but eradication of this infection has not yet been shown to reduce or eliminate the risk of developing this condition. The effect of H. pylori treatment in patients with gastroesophageal reflux disease is also unclear. There is a potential benefit in the prevention of atrophic gastritis but a potential disadvantage is the worsening of reflux disease, which has been suggested by certain studies. In addition, the interaction between H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) appears quite complicated. Although there have been several advances in the last 2 decades with regards to the treatment of H. pylori, several controversies still exist, attesting to the requirement for further research.     

In the European population HLA-class II genes are not associated with Helicobacter pylori infection.

OBJECTIVE : Genetic variability influences susceptibility to several diseases and depends on the specific ethnic background of individuals. HLA-class II genes have repeatedly been investigated as candidate genes for predisposition to Helicobacter pylori infection. Certain HLA-DQA1 alleles have been reported to be associated with gastric and duodenal ulcer disease in infected patients in the Japanese population. But conflicting results were reported on European and Japanese populations. METHODS : HLA-DRB1 typing of 382 German individuals with well-defined H. pylori status and different clinical course of the disease was performed by polymerase chain reaction and allele-specific oligonucleotide hybridization. RESULTS : No association with the infection status itself was observed in the German cohort. Similar results have been found in other European populations. In contrast, re-analysis of published data in a Japanese cohort revealed a highly significant association of DRB1*1501 with uninfected controls (P = 0.00035). In the German population, the carrier frequency of DRB1*15 was higher in H. pylori-positive individuals with gastric or duodenal ulcer but without statistical significance (gastric ulcer: odds ratio, 2.13; chi2 = 3.77; P = 0.05; Bonferroni correction, Pc = not significant; and duodenal ulcer: odds ratio, 2.15; chi2 = 3.4; P = 0.06; Pc = not significant). In infected individuals, autoantibodies to gastric mucosa were investigated, but no statistical significant difference in carrier frequencies of HLA-DRB1 alleles was evident. CONCLUSION : The DRB1*1501-DQA1*01021-DQB1*0602 haplotype seems to provide protection from H. pylori infection in the Japanese population, whereas genetic variability in HLA-class II genes has only a minor impact on H. pylori infection and its clinical course in the European population.     

Antibodies to human gastric epithelial cells and heat shock protein 60 in Helicobacter pylori positive mucosa associated lymphoid tissue lymphoma

BACKGROUND: Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori. AIM: To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. METHODS: Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and from H pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. CONCLUSIONS: Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.     

中国人群1型糖尿病HLA-DQ基因多态性的Meta分析

目的　综合评价中国人群HLA DQ基因多态性与 1型糖尿病 (DM)的关联性。方法　以 1型DM组和健康对照组的各HLA DQ等位基因频数(基因型频数、单倍型频数 )分布的OR值为统计量,全面检索相关文献;应用Meta分析软件包REVMAN4. 2,在基因分型水平上,对各研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果　等位基因DQA1* 0301、DQA1* 0501、DQB1* 0201、DQB1* 0303、DQB1* 0401和DQB1* 0604是中国人群 1型DM的危险基因 (均P<0. 05), 他们的合并OR值分别为2. 83、2. 90、4. 17、1. 65、2. 00和 3. 00;基因型 (或单倍型 )DQA1* 0301 /DQB1* 0201、DQA1* 0301 /DQB1*0302、DQA1* 0501 /DQB1* 0201、DQA1* 0301 /DQB1* 0201 /DRB1* 0301和DQB1* 0302 /DRB1* 0405是中国人群 1型DM的危险基因型(或单倍型,均P<0. 05),他们的合并OR值分别为 8. 95、3. 09、6. 01、6. 57和 14. 85。而等位基因DQA1* 0101、DQA1* 0102、DQA1* 0103、DQA1* 0104、DQA1* 0201、DQA1* 0401、DQA1* 0601、DQB1* 0301、DQB1* 0501、DQB1* 0503、DQB1* 0601和DQB1* 0602是中国人群 1型DM的保护等位基因(均P<0. 05),他们的合并OR值分别为 0. 47、0. 38、0. 21、0. 07、0. 44、0. 39、0. 44、0. 19、0. 33、0. 32、0. 42和 0. 28; 基因型     

Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H. pylori eradication and API2-MALT1 status

BACKGROUND AND AIM: Clinicopathologic characteristics and prognosis of Helicobacter pylori eradication-resistant gastric MALT lymphoma have not been well clarified. We analyzed a consecutive series of gastric MALT lymphomas at our institution regarding treatment, clinical course, and prognosis, with special reference to responsiveness to H. pylori eradication and presence of API2-MALT1. METHODS: Subjects were 92 consecutive patients with gastric MALT lymphoma. Seventy were H. pylori positive, and 87 received H. pylori eradication therapy. The remaining five cases were API2-MALT1 positive and did not receive eradication treatment. Second-line treatments were radiation therapy, total gastrectomy, and chemotherapy (rituximab, rituximab plus CHOP, or rituximab plus 2-chlorodeoxyadenosine). RESULTS: Gastric MALT lymphoma was classified into three groups, except one case with API2-MALT1 who responded to H. pylori eradication therapy: responders without API2-MALT1 (group A, N = 56, 65%), nonresponders without API2-MALT1 (group B, N = 16, 19%), and nonresponders with API2-MALT1 (group C, N = 14, 16%). Most cases in group A attained complete remission (CR) in 2 or 3 months and CR persisted for an average of 51.1 months (3-134 months). Recurrence was only seen in one case. In groups B and C, radiation therapy, chemotherapy, and total gastrectomy resulted in CR in 13, 5, and 2 cases, respectively. In 5 group B patients and 6 group C patients who did not undergo second-line therapy, disease did not progress for an average of 10.4 and 40.1 months, respectively. In 1 group C case who did not receive second-line treatment, lymphoma metastasized to the lung 12 yr after eradication. All group B patients and all but 2 group C patients remain alive; one of these deaths was from gastric carcinoma developing 7 yr after eradication. CONCLUSION: Gastric MALT lymphoma responding to H. pylori eradication demonstrated good prognosis, and for nonresponsive cases, second-line treatments resulted in CR. However, careful observation for development of gastric carcinoma and disease progression is essential during follow-up of API2-MALT1-positive MALT lymphoma when patients decline second-line treatment.