我国溃疡性结肠炎人类白细胞抗原-DR基因分型的研究

目的：研究溃疡性结肠炎（UC）患者的人类白细胞抗原－DR（HLA－DR）基因分型,并分析其与抗中性粒细胞胞浆抗体（ANCA）及疾病分型的关系。方法：用接免疫荧光法分别对80例UC患者和123例健康者进行血清ANCA检测,同时用序列特异性引物－聚合酶链反应法（PCR－SSP）对HLA－DR1到第4个基因位点进行分析。结果：UC患者ANCA的阳性率为55．0％,对照组均为阴性;UC患者HLA－DR2及DR15基因阳性率分别为58．8％和40．0％,较对照组30．1％、17．9％显著增高（P均＜0．05）;与ANCA（－）UC患者比较,ANCA（＋）UC的DR15基因阳性率显著增加,而DR16基因阳性率显著降低;慢性持续型UC DR2和DR15基因性率较其他型显著增加。结论HLA－DR2和ANCA在UC中阳性率均显著增加,在ANCA阳性和阴性的UC中,分别由DR15和DR16基因阳性率增加所致;HLA－DR基因分型与临床分型有关。     

HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease.

HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in the regulation of the immune system, expressed by HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and B) and II (DR) antigens were studied by serological techniques. Detection of ANCA was carried out in all patients by an indirect immunofluorescence method. The relative frequencies of HLA antigens were compared with a control group made up of 156 blood donors. The control group for the ANCA study was made up of 100 individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in patients with ulcerative colitis. No significant differences were found between patients with Crohn"s disease and controls regarding HLA typing. We detected a significant increase of HLA-DR3 in extensive forms of ulcerative colitis. Detection of ANCA was positive in 46% of the patients with ulcerative colitis and in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the association found between HLA-DR3 and extensive forms of ulcerative colitis provides evidence of genetic heterogeneity. The relationship between ANCA and HLA phenotype (although not significant) supports this concept.     

抗中性粒细胞胞浆抗体对维吾尔族及汉族溃疡性结肠炎的诊断意义

目的了解抗中性粒细胞胞浆抗体(ANCA)在新疆地区维吾尔族(维族)及汉族溃疡性结肠炎(UC)患者中的阳性率,确定其对维族及汉族UC的诊断及鉴别诊断意义,同时通过比较维族及汉族UC患者中ANCA的阳性率,了解是否存在同一地区不同种族UC的ANCA阳性率的差异,评价ANCA是UC遗传易感性标志的可能性.方法用间接免疫荧光法检测UC患者(维族39例,汉族31例)、腹泻患者(维族30例,汉族30例)及健康对照者(维族30例,汉族30例)的血清ANCA,比较不同组间及不同种族间ANCA的阳性率.结果UC组中维族及汉族的ANCA阳性率与对照组相比,差异均有显著性(P＜0.05);UC组中维族与汉族间的ANCA表达,差异亦有显著性(P＜0.05),ANCA在维族与汉族UC中的阳性率与病变范围及病情程度无关(P＞0.05).结论ANCA对UC具有较高的敏感性及特异性,是UC诊断的一个辅助手段,并具有鉴别诊断意义.同时提示,ANCA可能为UC遗传易感性的标志.     

Functional MICA-129 polymorphism and serum levels of soluble MICA are correlated with ulcerative colitis in Chinese patients

Background and Aim: The aim of the present study was to evaluate the contribution of the dimorphism (MICA‐129 val and met) to the genetic susceptibility and functions of ulcerative colitis (UC) in patients in central China. Methods: Genotyping of MICA‐129 was performed in 272 consecutive UC patients and 560 age‐ and sex‐matched healthy individuals by using a polymerase chain reaction‐sequencing based typing (PCR‐SBT) method. A total of 93 patients and 98 healthy individuals serum soluble MICA (sMICA) concentrations were detected by enzyme‐linked immunosorbent assay. Results: Both the frequencies of the variant allele (val) and genotype (val/val) in the MICA‐129 gene were significantly higher in UC patients than in the controls (77.4% vs 71.7%, P = 0.015, 95% confidence interval [CI]: 1.064–1.716; 56.9% vs 46.4%, P = 0.005, 95% CI: 1.142–2.047). Serum sMICA levels were significantly higher in UC patients than in the controls (560 ± 140 pg/mL vs 157 ± 67 pg/mL, P < 0.0001). The genotype also affected the extent and the activity of UC. Furthermore, patients with the MICA‐129 val/val genotype had higher serum sMICA levels than those with the val/met + met/met genotype (661 ± 352 SD pg/mL vs 523 ± 245 SD pg/mL, 95% CI: 13.47–265.35, P = 0.03). In addition, patients with severe colitis were more susceptible to higher levels of sMICA than those with mild colitis. Conclusions: Our findings showed that the MICA‐129 gene polymorphism as a functionally relevant gene was associated with UC and seems to play a potential role in the development of UC in patients in central China.     

Clinical characteristics and long‐term prognosis of elderly onset ulcerative colitis

Background and Aim

The aim of this study was to investigate the clinical characteristics and prognosis of patients with elderly onset ulcerative colitis (EOUC), a new growing subgroup of UC.

Methods

This study retrospectively analyzed 3060 South Korean UC patients diagnosed between 1977 and 2014. The clinical characteristics and prognosis of EOUC, defined as UC in those aged ≥ 60 years at diagnosis, were compared with those of non‐EOUC (NEOUC).

Results

Among the 3060 patients, 226 were diagnosed with EOUC (7.4%, median age at diagnosis 65.9 years [interquartile range, 62.9–68.7 years], 58.4% male). The frequency of EOUC increased from 3.9% in the interval 1977–1999 to 9.7% in the interval 2008–2014 (P < 0.001). There were more ex‐smokers in the EOUC than in the NEOUC group (44.2% vs 19.9%, P < 0.001). In the EOUC group, extensive colitis at diagnosis, and the maximum extent thereof, was less than in the NEOUC group (13.7% vs 22.6%, P = 0.002, and 34.5% vs 42.5%, P = 0.011, respectively). The 10‐year cumulative colectomy rate was significantly higher in the EOUC than in the NEOUC group (12.6% vs 7.7%, P = 0.015). UC‐related and all‐cause mortality were higher in the EOUC than in the NEOUC group (3.5% vs 0.6%, P < 0.001, and 12.4% vs 1.8%, P < 0.001, respectively).

Conclusion

Elderly onset ulcerative colitis patients are likely to exhibit distinct features both at diagnosis and during follow‐up. It is necessary to pay more attention to, and to conduct further studies on, this particular group of patients.     

Genetic polymorphism of methylenetetrahydrofolate reductase G1793A,hyperhomocysteinemia, and folate deficiency correlate with ulcerative colitis in central China

Background and Aims: Methylenetetrahydrofolate reductase (MTHFR) encoding genes were associated with ulcerative colitis in Chinese in our previous study. We further studied association of a new polymorphism of MTHFR G1793A with ulcerative colitis and assessed relationship of this polymorphism with hyperhomocysteinemia (HHcy, ≥ 15 mmol/L) and deficiency of folate (≤ 7 nmol/L) and vitamin B₁₂ (≤ 150 pmol/L) in a cohort of patients with ulcerative colitis in central China. Methods: A total of 252 patients and 654 healthy controls were recruited. Polymorphism of MTHFR G1793A was examined using a polymerase chain reaction‐restriction fragment length polymorphism method. Plasma levels of homocysteine (Hcy), folate and vitamin B₁₂ were determined by enzymatic cycling assay and corpuscle immune chemiluminescence assay, respectively. Results: Frequencies of alleles and genotypes in MTHFR G1793A gene differed significantly between ulcerative colitis patients and the healthy controls (20.83% vs 10.47%, 95% confidence interval [CI]: 1.703–2.972, P = 0.0006; 40.48% vs 19.88%, 95% CI: 1.997–3.761, P = 0.0002, respectively). Plasma Hcy levels were higher and folate and vitamin B₁₂ concentrations were lower in the patients than in the healthy controls (21.72 ± 6.59 vs 12.47 ± 5.02, 95% CI: ?10.93–?7.58, P < 0.0001; 11.25 ± 6.19 vs 15.28 ± 7.72, 95% CI: 2.03–6.04; P < 0.001; 322.81 ± 128.47 vs 442.59 ± 129.36, 95% CI: 62.61–136.95, P < 0.0001, respectively). HHcy and folate deficiency were more prevalent in patients with ulcerative colitis (45.32% vs 26.17%, 95% CI: 1.285–4.378, P = 0.005; 30.68% vs 13.0%, 95% CI: 1.416–6.197, P = 0.003, respectively). Conclusions: MTHFR G1793A gene polymorphism, HHcy, folate deficiency and low vitamin B₁₂ concentration were associated with ulcerative colitis in central China. Our findings demonstrate that the Hcy‐related gene and metabolites are involved in pathogenesis of ulcerative colitis.     

HLA-DRB1*1502 confers susceptibility to ulcerative colitis,but is negatively associated with its intractability: a Korean study

BACKGROUND AND AIMS: Several studies have documented the high incidence of several HLA class II alleles in Japanese patients with ulcerative colitis (UC). Although the characteristics of the HLA system in Koreans are quite similar to those in the Japanese, it is not clear whether the HLA pattern in Korean UC is similar to that in Japanese UC. We investigated an association between HLA class II genes and UC patients and the clinical meaning of these genes in Korea. PATIENTS AND METHODS: Unrelated Korean patients with UC ( n=70) and ethnically matched unrelated controls ( n=182) were genotyped for HLA-DR by PCR followed by reverse hybridization using sequence-specific oligonucleotide probes. The clinical characteristics of the patients were analyzed with regard to anti-neutrophil cytoplasmic antibody (ANCA) status and total colectomy for intractability. RESULTS: HLA-DR2 and DRB1*1502 were found significantly more frequently in patients (42.9% and 21.4%) than controls (20.3% and 5.5%). DRB1*1502 was more frequent in p-ANCA-positive (5/23) than in p-ANCA-negative (1/11) patients. Total colectomy for intractability was performed more commonly in patients without DRB1*1502 (14/55) than in those with it (0/15). CONCLUSIONS: Our data are consistent with those of Japanese studies in that DR2 and DRB1*1502 are positively associated with UC patients. In contrast to the Japanese study, however, our results demonstrates that DRB1*1502 is negatively associated with the risk of colectomy in Korean patients with UC.     

Association of hla–dr and hla–dq antigens with congenital dislocation and dysplastic osteoarthritis of the hip joints in japanese people

Objective. To investigate the frequency of HLA-DR and DQ antigens among patients with congenital dislocation of the hip joint or dysplastic osteoarthritis (OA) and to determine whether tissue typing might contribute to better understanding of these disorders. Methods. HLA–DR and DQ typing was undertaken in 18 patients with congenital dislocation of the hip joints, 65 patients with dysplastic OA of the hip, 42 patients with primary OA of the knee, and 40 normal controls. Typing for HLA–D antigens was performed using the standard microlymphocytotoxicity method. Results. The frequency of HLA–DR4 in patients with congenital dislocation of the hip joint (61.1%) and patients with dysplastic OA of the hip (58.5%) was significantly increased compared with normal controls (27.5%) (P_corr < 0.05 and P < 0.01, respectively). The relative risk for HLA–DR4 was 4.1428 and 3.7104, respectively, in these 2 disease groups. The frequency of HLA–DR4 in the patients with primary OA of the knee (35.7%) did not differ significantly from that in normal controls. Conclusion. The results strongly indicate that development of congenital dislocation of the hip joint and progression of dysplastic OA of the hip are associated with genes of the HLA–D region.     

Association of tap2 polymorphism with rheumatoid arthritis is secondary to allelic association with hla–drb1

Objective. To study polymorphisms of the newly described TAP2 locus in rheumatoid arthritis (RA) and to analyze their relationship with HLA–DRB1 alleles previously implicated in the development of the disease. Methods. TAP2 polymorphic residues at 3 sites, Val/Ile-379, Ala/Thr-565, and Ala/Thr-665, were characterized by amplification refractory mutation system polymerase chain reaction in 185 RA patients and 48 HLA–DR4 positive healthy controls. HLA-DR4 subtypes were determined by sequence-specific priming and oligonucleotide hybridization. Results. The frequencies of Ile-379, Thr-565, and Thr-665 were significantly increased in DR4 positive versus DR4 negative RA patients. TAP2 genotype distributions also differed between the patient groups stratified by DR4 status. However, no significant differences in TAP2 polymorphisms were observed between DR4 positive RA patients and DR4 positive controls, although relationships between specific DR4 subtypes and TAP2 variants were identified. Conclusion. Particular TAP2 polymorphisms are associated with distinct HLA–DR specificities in both normal and RA populations. Thus, the prevalence of specific TAP2 residues and genotypes in RA appears to be secondary to the HLA–DR frequencies and genotypic combinations that are typical of RA.     

Novel genetic markers of rheumatoid arthritis in chilean patients,by dr serotyping and restriction fragment length polymorphism analysis

Objective. The analysis of genetic markers of rheumatoid arthritis (RA) in a population in which the DR4 serotype is not strongly associated with the disease. Methods. Chilean RA patients (56 seropositive and 22 seronegative) and 141 controls were studied by serotyping. Southern blot analysis of Bam HI restriction fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with seropositive RA, 17 patients with seronegative RA, and 45 controls, using a complementary DNA probe specific for DRB1 genes. Results. The prevalence of the HLA—DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in controls (3%) (P_corr < 0.0008, by Fisher's exact test; relative risk [RR] = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased, did not achieve a significant preponderance. The simultaneous presence of two Bam HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive patients (83%; RR = 9; P_corr < 0.00002) than in controls (36%), and seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its prevalence remained increased in comparisons of DR4 positive controls (36%) with DR4 positive seropositive patients (100%; RR = 67; P_corr < 0.0002) and DR4 positive seronegative patients (100%; RR = 36; P_corr < 0.006), even after excluding the DR9 positive individuals. A tendency toward higher association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4 or DR9 positive individuals, than in DR1 positive controls (14%), was also observed. Conclusion. The HLA—DR9 haplotype was definitively consolidated as a very strong genetic marker exclusively for seropositive RA in Chilean patients, as suggested by our previous observations. RFLP analysis showed that the simultaneous presence of 3.6-kb and 4.5-kb Bam HI fragments constituted a better RA marker than did any of the heretofore studied haplotypes. These fragments together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes. The overall evidence indicates that Chilean seropositive RA patients display a genetic background that is different from that underlying RA susceptibility in other populations and suggests the existence of common, as well as distinct, genetic elements predisposing to seronegative and seropositive RA.     

Evidence of a Genetic Basis for the Different Geographic Occurrences of Liver/Kidney Microsomal Antibody Type 1 in Hepatitis C

Antibodies to liver/kidney microsome type 1 occur in Italian patients with hepatitis C, but rarely develop in North American patients. Our goals were to compare the frequencies of the HLA markers associated with autoimmune expression in Italian and North American patients with chronic hepatitis C and to determine genetic bases for regional differences in antibody production. HLA B8, DR3, DR4, DR7, DR11, DR13, DQ2, and the B8-DR3-DQ2 haplotype were determined by microlymphocytotoxicity and polymerase chain reaction in 105 Italian patients (50 with microsomal antibodies), 100 North American patients (none with microsomal antibodies), and Italian and North American healthy control subjects. Italian patients with microsomal antibodies differed from North American patients without these antibodies by having a higher frequency of HLA DR7 (54% vs. 27%, P=0.002). HLA DR7 occurred more frequently in seropositive Italian patients than in seronegative counterparts (54% vs. 11% P < 0.0001), Italian healthy control subjects (54% vs. 29%, P=0.0009), and North American healthy control subjects (54% vs. 19%, P < 0.0001). The frequency of HLA DR7 was similar in North American patients and controls (27% vs. 19%, P=0.2), but it was lower than in Italian controls (19% vs. 29%, P=0.059). Seropositive Italian patients had a lower frequency of HLA DR11 than seronegative Italian patients and Italian controls (18% vs. 34%, P=0.07, and 18% vs. 35%, P=0.02, respectively). In contrast to seropositive Italian patients, North American patients had HLA DR4 (30% vs. 12%, P=0.02), HLA DR13 (29% vs. 10%, P=0.01), and the B8-DR3-DQ2 haplotype (23% vs. 6%, P=0.01) more often. Similarly, HLA DR4 and the B8-DR3-DQ2 phenotype were more frequent in North American patients than in Italian controls (30% vs. 16%, P=0.005, and 23% vs. 7%, P=0.00002, respectively). HLA DR7 is associated with the development of microsomal antibodies in Italian patients with chronic hepatitis C. The lower frequency of HLA DR7 in North America could contribute to the rarity of these antibodies in this region. HLA DR11 may be protective against the development of microsomal antibodies in Italian patients, whereas HLA DR4, HLA DR13, and the B8-DR3-DQ2 haplotype may be protective in North American patients.     

HLA‐C and KIR combined genotype as new response marker for HBeAg‐positive chronic hepatitis B patients treated with interferon‐based combination therapy

Current treatment for chronic hepatitis B infection (CHB) consists of interferon‐based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA‐C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA‐C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa‐2a + adefovir. Genotyping of killer immunoglobin‐like receptors (KIRs) was performed by SSP‐PCR. One SNP in HLA‐C (rs2308557) was significantly associated with combined response in HBeAg‐positive CHB patients (P = 0.003). This SNP is linked to the HLA‐C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA‐C2 was observed significantly more often in HBeAg‐positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1‐C2 predicted response independent of HBV genotype and ALT at baseline. HLA‐C and KIR genotype is strongly associated with response in HBeAg‐positive CHB patients treated with interferon‐based therapy. In combination with other known response markers, HLA‐C/KIR genotype could enable the selection of patients more likely to respond to interferon‐based therapy.     

HLA–DRB4 as a genetic risk factor for Churg‐Strauss syndrome

Objective

To explore the association between HLA alleles and Churg‐Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease.

Methods

Low‐resolution genotyping of HLA–A, HLA–B, and HLA–DR loci and genotyping of TNFA −238A/G and TNFA −308A/G single‐nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls.

Results

The frequency of the HLA–DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; χ² = 12.64, P = 0.0003, corrected P [P_corr] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47–3.99). The HLA–DRB4 gene, present in subjects carrying either HLA–DRB1*04, HLA–DRB1*07, or HLA–DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; χ² = 16.46, P = 0.000058, P_corr = 0.000232, OR 2.49, 95% CI 1.58–3.09). Conversely, the frequency of the HLA–DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; χ² = 7.62, P = 0.0057, P_corr = 0.0228, OR 0.54, 95% CI 0.35–0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)–positive, with features of small‐vessel vasculitis, and ANCA‐negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA–DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001).

Conclusion

These findings indicate that HLA–DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.

     

Polymorphisms in tumour necrosis factor and adhesion molecule genes in patients with inflammatory bowel disease: associations with HLA-DR and -DQ alleles and subclinical markers

BACKGROUND: When investigating susceptibility to inflammatory bowel disease (IBD), a multifactorial disorder with a genetic predisposition, polymorphisms of molecules with immunoregulatory function are of potential interest. This is the first time that the polymorphisms of HLA-DR and -DQ, tumour necrosis factor (TNF), E-selectin (CD62E), L-selectin (CD62L), and intercellular adhesion molecule 1 (ICAM-1, CD54) were determined in Estonians, a population with a low IBD incidence rate, and their occurrence investigated in subgroups of a total of 53 IBD patients. METHODS: The reverse hybridization principle and sequence specific primers were used for HLA genotyping. To analyse the TNF and adhesion molecule polymorphisms, the polymerase chain reaction with subsequent restriction fragment length polymorphism or single-strand conformation polymorphism method was used. RESULTS: In the subgroup of antineutrophil cytoplasmic antibody (ANCA)-positive ulcerative colitis (UC) patients we found a higher frequency of the TNF2 (20.8% versus 0.0% in ANCA-negative UC patients, P = 0.051) and HLA-DRB1*15 allele (35.4% versus 15.7% in controls; P = 0.004). Of ANCA-positive UC patients 87.5% were carriers of one of these alleles (22.2% among ANCA-negative UC patients (P<0.001, Pc = 0.039) and 51.4% among controls (P = 0.002). Specific typing of HLA-DRB1*15 alleles showed that the HLA-DRB1*1501 allele was responsible for the HLA-DRB1*15 association with ANCA-positive UC. Associations of ICAM-1, E-selectin, or L-selectin polymorphisms with IBD were not found. CONCLUSIONS: TNF2 and HLA-DRB1*15 alleles were associated with ANCA-positive UC in the investigated population. ANCA might be a useful marker, at least in some ethnic groups, for dividing IBD patients into genetically more homogeneous subgroups.     

Appendectomy, tonsillectomy, and risk of inflammatory bowel disease: a case control study in Iran

There is some controversy about the prevalence of appendectomy and tonsillectomy among patients with Crohns disease and a lower rate of appendectomy among patients with ulcerative colitis (UC). The objective of this study was to elucidate the role of appendectomy and tonsillectomy in Iranian patients with inflammatory bowel disease (IBD). Three hundred and eighty-two consecutive cases of UC and 46 cases of CD were included. Age and sex-matched controls were randomly selected. A total of 382 controls for UC and 184 controls for CD were enrolled. A standard record concerning smoking habit, history of appendectomy and tonsillectomy, OCP, and NSAID use was completed. Logistic regression analysis was used to evaluate potential confounding variables. Twelve patients (3.1%) with UC reported a previous history of appendectomy compared with 30 controls (7.9%) (OR=0.38, 95%CI=0.19–0.76, P<0.004). Appendectomy was reported by five patients (10.9%) with CD compared with four controls (2.2%) (OR=5.49, 95%CI=1.41–21.34, P<0.02). The logistic regression analysis showed that appendectomy is a risk factor in CD but has a modest protective effect for development of UC. No association with tonsillectomy was found for either disease. A statistically significant protective effect for smoking in UC was found (OR=0.2, 95%CI=0.13–0.32, P<0.0001). We have found an inverse association between OCP and NSAID use with UC, but not CD (P<0.0001 and P<0.001, respectively). Appendectomy is protective in UC, but a risk factor in CD among Iranian population. Tonsillectomy was not associated with either UC or CD disease. UC, but not CD, is a disease of non-smokers. The inverse association between ulcerative colitis and OCP or NSAID in the Iranian population is noted.     

Clinical significance of expression of tissue factor and tissue factor pathway inhibitor in ulcerative colitis

AIM: To investigate the clinical significance of expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in ulcerative colitis (UC).METHODS: Thirty UC specimens taken by colonoscopy from patients with active UC treated at the Department of Pathology, Central Hospital Affiliated to Shenyang Medical College from February 2010 to January 2012 were included in an experimental group, and 30 normal colon tissue samples taken by colonoscopy from non-UC patients were included in a control group. Expression of TF and TFPI in UC and normal colon tissue samples was detected by immunohistochemistry.RESULTS: The positive rate of TF in UC was significantly higher than that in normal colon tissue (63% vs 33%, χ² = 5.41, P < 0.05). The positive rate of TFPI in UC was also significantly higher than that in normal colon tissue (43% vs 17%, χ² = 5.08, P < 0.05).CONCLUSION: Positive rates of TF and TFPI expression in UC are significantly higher than those in normal colon tissue. TF and TFPI may play an important role in the pathogenesis of UC.     

Polymyalgia rheumatica: a syndrome associated with hla–dr4 antigen

HLA class II antigens were determined in 65 patients with biopsy-proven giant cell arteritis (GCA). An increase in DR4 antigen frequency was found in the patients (40%) compared with that in 200 healthy controls (20%) (Pcorr < 0.05). DR4 was significantly more frequent in GCA patients with polymyalgia rheumatica (PMR) than in those without PMR (58.8% versus 19.3%) (P < 0.005). HLA–DR4 frequency in GCA patients without PMR was similar to that in the control population (20%). Patients with severe, disabling PMR had DR4 more frequently (90%) than did those with moderate symptoms who required medical care because of cranial arteritis manifestations (41.6%) (P < 0.05). We conclude that, in GCA patients, association with DR4 is mainly related to the manifestation of the disease as PMR. We discuss clinical and immunogenetic similarities between PMR and other DR4-associated rheumatic disorders. Common immunopathogenic mechanisms leading to clinical overlap among them are suggested.     

Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne

Background and Aim: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential. Methods: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK. Results: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex‐smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti‐tumor necrosis factor agent. Conclusions: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK.     

Susceptibility to relapsing polychondritis is associated with hla–-dr4

Objective. To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). Methods. HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA–DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. Results. A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (P_corr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. Conclusion. There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions.