Some specific human leukocyte antigen (HLA)-DR/DQ haplotypes are more important than individual HLA-DR and -DQ phenotypes for the development of mucocutaneous type of Behçet''s disease and for disease shift from recurrent aphthous stomatitis to mucocutaneous type of Behçet''s disease

Abstract: The phenotype and haplotype frequencies of human leukocyte antigens (HLA)‐DR and ‐DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behçet’s disease (BD) were calculated and compared with those in 310 healthy control Chinese and with those in 80 Chinese patients with recurrent aphthous stomatitis (RAS). We found that the phenotype frequency of HLA‐DRw8 [corrected P (P_c)<0.005] and the haplotype frequencies of HLA‐DRw8/DQw1 (P_c<0.005), ‐DRw8/DQw5(w1) (P_c<0.0005), ‐DRw12(5)/DQw1 (P_c<0.005), ‐DRw12(5)/DQw6(w1) (P_c< 0.0005), and ‐DRw52/DQw1 (P_c<0.005) in patients with the MC type of BD were significantly greater than those in healthy control subjects. This finding suggests that individual Chinese with HLA‐DRw8 antigen and HLA‐DRw8/DQw1, ‐DRw8/DQw5(w1), ‐DRw12(5)/DQw1, ‐DRw12(5)/DQw6(w1) and ‐DRw52/DQw1 haplotypes are more likely to have the MC type of BD. Furthermore, the relative risks (RRs) of HLA–DRw8/DQw1 (5.6), ‐DRw8/DQw5 (w1) (10.0), and ‐DRw12(5)/DQw6(w1) (14.4) haplotypes in patients with the MC type of BD were equal to or higher than the RR of HLA‐DRw8 phenotype (5.6), suggesting that some of the HLA‐DR/DQ haplotypes may play more important roles than the individual HLA‐DR and ‐DQ phenotypes for the development of the MC type of BD. The phenotype frequencies of HLA‐DR5 (P_c<0.01), ‐DRw8 (P_c<0.005) and ‐DQw1 (P_c<0.05) as well as the haplotype frequencies of HLA‐DR5/DQw1 (P_c<0.005) and ‐DRw8/DQw1 (P_c<0.00005) in patients with the MC type of BD were significantly higher than those in patients with RAS. Moreover, the RRs of HLA‐DR5/DQw1 (29.1) and ‐DRw8/DQw1 (47.4) haplotypes were greater than the RRs of HLA‐DR5 (10.4), ‐DRw8 (23.4) and ‐DQw1 (4.0) antigens. These results suggest that some specific HLA‐DR/DQ haplotypes may be more important than the individual HLA‐DR and ‐DQ phenotypes in the disease shift from RAS to the MC type of BD.     

Oral mucosal Langerhans cells express DR and DQ antigens

The expression of the Class II antigens HLA-DR and HLA-DQ in human oral mucosa was examined in health and in the presence of inflammation. DQ antigens were detected on dendritic intra-epithelial cells which expressed the Langerhans cells (LC) phenotype T6+, DR+. In healthy gingiva, DR and DQ were co-expressed on Langerhans cells, whereas in an experimental gingivitis (day 8), more LC expressed DR than DQ. Absolute LC numbers were increased in inflammation. Traumatic ulceration of the buccal mucosa resulted in a decrease in the density of T6-, DR-, and DQ-positive cells. Repopulation of migrating and regenerated epithelium was complete 10 days after ulcer induction. Disparity between DR and DQ expression was seen in both normal buccal mucosa and throughout the ulcer healing period. These results are in agreement with the reported sequence of Class II antigen expression on lymphoid cells.     

Analysis of HLA antigens in Japanese with oral lichen planus

Analysis of HLA antigens was performed in 42 Japanese patients with oral lichen planus (OLP). There were no significant differences in the frequency of HLA-A, B, C antigens between OLP-patients and control subjects, although a decreasing trend in the frequency of Bw 52 and an increasing trend in that of Bw 61 and Cw 3 was noted. Among the HLA-DR and DQ antigens studied, the frequency of DRw 9 was significantly increased (Pc<0.05, RR = 3.3) and the relative risk was increased (RR = 6.0) when DRw 9 was carried on as a Bw 61/DRw 9 haplotype. Our results suggest that HLA-associated genetic factors play a role to some extent in the development of OLP.     

Analysis of HLA antigens in Japanese with oral lichen planus

Analysis of HLA antigens was performed in 42 Japanese patients with oral lichen planus (OLP). There were no significant differences in the frequency of HLA-A, B, C antigens between OLP-patients and control subjects, although a decreasing trend in the frequency of Bw 52 and an increasing trend in that of Bw 61 and Cw 3 was noted. Among the HLA-DR and DQ antigens studied, the frequency of DRw 9 was significantly increased (Pc less than 0.05, RR = 3.3) and the relative risk was increased (RR = 6.0) when DRw 9 was carried on as a Bw 61/DRw 9 haplotype. Our results suggest that HLA-associated genetic factors play a role to some extent in the development of OLP.     

Langerhans cells expressing HLA-DQ, HLA-DR and T6 antigens in normal oral mucosa and lichen planus

We compared Langerhans cells (LC) expressing HLA-DQ, HLA-DR and T6 antigens in biopsies from the same oral mucosal site in 12 patients with oral lichen planus and eight healthy volunteers. LC expressing each antigen were observed in all the specimens, but in lichen planus the cells were located in higher levels of the epithelium than in controls. Compared with controls, lichen planus contained significantly more HLA-DQ-positive LC (P = 0.04) and fewer HLA-DR-positive LC (P = 0.05), but there was no such difference in T6-positive LC. In lichen planus specimens, there were significantly more LC expressing HLA-DQ and T6 than HLA-DR (P = 0.0001 and 0.02 respectively); no such differences were found in normal mucosa. Epithelial cells in lichen planus expressed HLA-DR antigen, but not HLA-DQ or T6 antigens. We conclude that in lichen planus there is modulation of HLA-DR and HLA-DQ antigen expression by LC, or differences in the number of LC expressing those antigens.     

Class I and II HLA antigens in British patients with oral lichen planus

The frequencies of human leukocyte antigens—HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ1—were determined in a group of 40 white British patients with oral lichen planus and compared with those of healthy controls. Alterations in the frequencies of several HLA antigens were noted. In particular, an increase in HLA-Bw57 and a decrease in the frequency of HLA-DQ1 were seen in the group with lichen planus. When different clinical subgroups of lichen planus were compared with the control group, significant changes were also noted in the frequencies of HLA antigens. This suggests that lichen planus may represent a heterogeneity of diseases and that HLA-Bw57 may predispose a person to lichen planus whereas HLA-DQ1 may be associated with resistance to it.     

HLA-DR and DQ antigens in Chinese patients with oral lichen planus

A study of HLA-DR and DQ typing in 44 patients with oral lichen planus (OLP) (28 women and 16 men) and in 107 normal controls of both sexes was performed by using Terasaki's oriental tray. Twenty-eight patients had erosive forms of lichen planus (OLPe). Serologic typing revealed a highly significant increase of HLA-DR 9 and Te 22 antigens in the patient group. Considering our findings and those in other autoimmune diseases, it is hypothesized that OLP is a localized autoimmune disease and the HLA-DR9 in Chinese takes the place of HLA-DR3 in Caucasians in carrying the genes which predispose to the development of autoimmune disease.     

复发性口腔溃疡患者口腔中的幽门螺杆菌

初步探讨复发性口腔溃疡（ｒｅｃｕｒｒｅｎｔｏｒａｌｕｌｃｅｒ,ＲＯＵ）患者的发病与其口腔中的幽门螺杆菌（ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）之间的关系。方法：通过聚合酶链反应（ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ,ＰＣＲ）,对每位ＲＯＵ患者口腔中６个不同牙位龈上、龈下共１２份菌斑进行检测,同时设立健康对照组,比较两组检测结果。结果：共检测ＲＯＵ患者７２例,对照组９４例;Ｈｐ阳性率     

Characterization of mononuclear cells in cyclosporin A induced gingival enlargement

Abstract – Gingival biopsies from five patients with cyclosporin A (CsA) induced enlargement of the gingiva contained prominent mononuclear infiltrates beneath the epithelial basement membrane. These infiltrates and surrounding tissues were studied using monoclonal antibodies directed against lymphocytes and their subgroups (OKT 3, OKT 4, OKT 8, Leu 3 and Leu 4), monocytes (OKM 1) and the framework structure of HLA-DR antigens (OKI al). As revealed by the reactivity of these antibodies the vast majority of the mononuclear cells in two individuals consisted of monocytes and in the others of T-Iymphocytes. Virtually no B-lymphocytes were observed. The ratio between T-cells bearing T 4 and T 8 antigens, in separate biopsies, varied between 6 and 0.3. Control biopsies were obtained from the gingiva of seven healthy individuals without gingivitis. These biopsies contained relatively few mononuclear cells all of which had T-lymphocytc phenotype.     

洁治爽漱口液治疗口腔粘膜病的临床疗效研究

目的观察洁治爽漱口液对口腔粘膜炎（复发性口腔溃疡、糜烂型口腔扁平苔藓）的临床疗效。方法对156例口腔粘膜炎患者进行临床研究,随机分为试验1组43例,试验2组39例（洁治爽漱口液组）,对照1组41例,对照2组33例（多贝尔氏液组）。结果洁治爽组治疗复发性口腔溃疡,糜烂型口腔扁平苔藓的显效数、总有效数明显高于多贝氏液组（P＜0.05）;洁治爽漱口液对复发性口腔溃疡、糜烂型扁平苔藓的疗效无显著性差异（P＞0.05）。结论洁治爽漱口液对口腔粘膜炎的治疗有明显疗效,是一种新型中药漱口认。     

Vesiculobullous mucocutaneous disease: pemphigus vulgaris

Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous disease in which oral lesions may be the initial and predominant manifestation. The disease is characterized by acantholysis in the immediately suprabasal layers of the stratified squamous epithelium, giving rise to blisters which readily rupture leaving erosions which show little tendency to heal. Immunogenetic studies indicate a marked genetic susceptibility to the disease, with the immune response-associated HLA-DR4 and DRw6 alleles being especially important. The trigger for autoantibody formation is unknown. The antigen in pemphigus vulgaris is probably a 130-140 kD cell adhesion molecule located in the cell membrane of basal and immediately suprabasal keratinocytes. Antibody binding to this antigen is likely to interfere with normal intercellular adhesion, leading to desmosomal detachment. Propagation of acantholysis and cell damage are attributable to complement activation, with deposition of the membrane attack complex on the keratinocyte cell membrane, and proteolysis due to increased plasminogen activator production. Steroid therapy is the treatment of choice, but significant mortality is still associated with the disease.     

Expression of CD1 and HLA-DR by Langerhans cells (LC) in oral lichenoid drug eruptions (IDE) and idiopathic oral lichen planus (LP)

Numbers of Langerhans ceils (LC) expressing the common thymocyte antigen (T6/CD1) are similar in oral lichen planus (LP) and in normal oral epithelium: however, expression of class II major histocompatibility antigens (HLA-DR/Ia) by Langerhans cells is greater in lichen planus than in normal epithelium, a phenomenon believed to be associated with activation and antigen presentation. This study quantified the numbers of T6+ve and HLA-DR + ve Langerhans cells in oral lichen planus and lichenoid drug eruptions (LDE) to investigate whether differences may reflect differing routes of antigen presentation. Six patients with oral lichenoid drug eruptions and six control idiopathic oral lichen planus patients had lesional biopsies. An immunoperoxidase technique was used to demonstrate binding of T6 and HLA-DR antibodies to identify dendritic intra-epithelia! cells as Langerhans cells and activated Langerhans cells, respectively. In lichenoid drug eruptions, the number of HLA-DR+ve LC was significantly lower than the number of T6+ve LC ( P < 0.05), whereas in idiopathic lichen planus the numbers of T6+ve and HLA-DR+ve LC did not differ significantly ( P = 0.20). The results provide evidence for differences in the routes of antigen presentation in lichenoid drug eruptions and idiopathic lichen planus.     

抗核抗体和T细胞免疫异常在口腔扁平苔藓和复发性口腔溃疡及慢性盘状红斑狼疮患者中的比例

目的比较口腔扁平苔藓（OLP）、复发性口腔溃疡（ROU）和慢性盘状红斑狼疮（DLE）患者自身抗核抗体（ANA）和T细胞免疫异常的差别,为探讨其发病机制奠定基础。方法流式细胞仪检测口腔扁平苔藓、复发性口腔溃疡和慢性盘状红斑狼疮患者外周血血清T细胞亚群,间接免疫荧光法检测ANA,比较ANA和T细胞免疫异常的比例。结果口腔扁平苔藓、复发性口腔溃疡和慢性盘状红斑狼疮3组患者间ANA的阳性率,慢性盘状红斑狼疮组为29.0%（9/31）,口腔扁平苔藓组为6.25%（5/80）,复发性口腔溃疡组为1.7%（2/115）。CD3＋细胞在3组中均以降低占最大比例,其中复发性口腔溃疡组为52.2%（60/115）,慢性盘状红斑狼疮组为51.6%（16/31）,口腔扁平苔藓组为50%（40/80）。CD4＋细胞在口腔扁平苔藓组以正常占最大比例,为75%（60/80） 而在慢性盘状红斑狼疮组却以降低占最大比例,为54.8%（17/31）。结论3组患者间的ANA阳性率和T细胞亚群检测结果差异均有统计学意义。     

健脾解毒汤治疗复发性口腔溃疡的疗效观察

目的:探讨使用健脾解毒汤治疗复发性口腔溃疡(ROU)的疗效.方法:将80 例ROU患者随机分为2 组,对照组采用康复新液局部治疗,治疗组在此基础上服用健脾解毒汤进行治疗,观察期为24 周.按照中华口腔医学会口腔黏膜病专业委员会制定的"复发性口腔溃疡疗效评价试行标准"进行疗效评价.结果:2 组患者在观察期内的总间歇时间均延长,总溃疡数均减少.2 组疗效比较,治疗组疗效优于对照组(P<0.05);治疗组ROU间歇期的延长优于对照组(P<0.01);ROU溃疡样数目的减少也优于对照组(P<0.01).结论:健脾解毒汤辅助治疗复发性口腔溃疡的临床疗效优于康复新单独使用.     

Characterization of mononuclear cells in cyclosporin A induced gingival enlargement

Gingival biopsies from five patients with cyclosporin A (CsA) induced enlargement of the gingiva contained prominent mononuclear infiltrates beneath the epithelial basement membrane. These infiltrates and surrounding tissues were studied using monoclonal antibodies directed against lymphocytes and their subgroups (OKT 3, OKT 4, OKT 8, Leu 3 and Leu 4), monocytes (OKM 1) and the framework structure of HLA-DR antigens (OKI al). As revealed by the reactivity of these antibodies the vast majority of the mononuclear cells in two individuals consisted of monocytes and in the others of T-lymphocytes. Virtually no B-lymphocytes were observed. The ratio between T-cells bearing T 4 and T 8 antigens, in separate biopsies, varied between 6 and 0.3. Control biopsies were obtained from the gingiva of seven healthy individuals without gingivitis. These biopsies contained relatively few mononuclear cells all of which had T-lymphocyte phenotype.     

Gingival keratinocytes express HLA-DR antigens in chronic gingivitis

The expression of the histocompatibility antigens HLA-DR and HLA-A, B, C within periodontally diseased tissue was investigated using immunohistological and histochemical techniques. Tissue was obtained from 18 patients with periodontal disease and from 2 healthy volunteers. HLA-DR antigen was expressed by the keratinocytes of the oral epithelium in all inflamed samples but was not a feature of normal tissue where HLA-DR reactivity was confined to Langerhans cells. These results are consistent with an underlying cellular immune process. Using a variety of phenotypic markers it was possible to characterize the macrophage population within the connective tissue into 2 distinct types: an antigen-presenting cell type located subjacent to the oral epithelium and a phagocytic cell type situated deep within the connective tissue.     

Gingival keratinocytes express HLA-DR antigens in chronic gingivitis

The expression of the histocompatibility antigens HLA-DR and HLA-A, B, C within periodontally diseased tissue was investigated using immunohistological and histochemical techniques. Tissue was obtained from 18 patients with periodontal disease and from 2 healthy volunteers. HLA-DR antigen was expressed by the keratinocytes of the oral epithelium in all inflamed samples but was not a feature of normal tissue where HLA-DR reactivity was confined to Langerhans cells. These results are consistent with an underlying cellular immune process. Using a variety of phenotypic markers it was possible to characterize the macrophage population within the connective tissue into 2 distinct types: an antigen-presenting cell type located subjacent to the oral epithelium and a phagocytic cell type situated deep within the connective tissue.     

口腔扁平苔藓与HLA的相关性研究

目的：探讨口腔扁平苔藓与人类白细胞抗原的相关性。方法：应用微量淋巴细胞毒试验,检测１９例上海汉族人口腔扁平苔藓外周血的人类白细胞抗原（ＨＬＡ－Ａ、－Ｂ、－ＤＲ、－ＤＱ）的抗原频率。结果：患者组ＨＬＡ－ＤＲ１抗原频率（３６．８４％）较正常对照组（１．０８％）显著增高（Ｐ＜０．００１）。结论：ＨＬＡ－ＤＲ１与口腔扁平苔藓明显相关。带有ＨＬＡ－ＤＲｌ相关基因的个体对口腔扁平苔藓具有遗传易感性     

Levamisole and/or Chinese medicinal herbs can modulate the serum level of squamous cell carcinoma associated antigen in patients with erosive oral lichen planus

Abstract: The serum levels of squamous cell carcinoma associated antigen (SCCA) were determined by a microparticle enzyme immunoassay in a group of patients with stage I oral squamous cell carcinoma (OSCC), major or minor type erosive oral lichen planus (EOLP), recurrent aphthous stomatitis (RAS), Behçet’s disease (BD), oral leukoplakia (OL), or oral submucous fibrosis (OSF), and in normal control subjects. About 97% of the normal control subjects and the patients with minor type EOLP, RAS, BD, OL or OSF had a serum level of SCCA within the normal limit of 1.2 ng/ml. However, 6 of the 12 (50%) patients with stage I OSCC and 14 of the 31 (45.2%) patients with major type EOLP had a serum level of SCCA greater than 1.2 ng/ml. The mean serum level of SCCA in stage I OSCC patients (1.38±1.16 ng/ml) or in major type EOLP patients (1.32±1.23 ng/ml) was significantly higher than that in normal control subjects (P<0.001) and that in the patients with minor type EOLP (P<0.001), RAS (P<0.001), BD (P<0.05), OL (P<0.05), or OSF (P<0.05). Either major or minor type EOLP patients could obtain a significant mean reduction of the serum SCCA level of 0.34–0.63 ng/ml after treatment with levamisole and/or Chinese medicinal herbs for 1–30 months. Combination therapy with levamisole plus Chinese medicinal herbs could achieve a shorter duration of treatment to get complete remission than the single therapy with either levamisole only or Chinese medicinal herbs only. We conclude that levamisole and/or Chinese medicinal herbs can modulate the serum SCCA level in EOLP patients. SCCA may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of EOLP. For EOLP patients, the combination therapy is superior to the single therapy of levamisole or of Chinese medicinal herbs.     

IL-23R基因多态性与复发性口腔溃疡易感性及临床疗效的相关性分析

目的：探讨白细胞介素 23 受体（Interleukin- 23 receptor,IL-23R）rs11465817 和 rs10489629位点基因多态性与复发性口腔溃疡（recurrent oral ulcer,ROU）易感性及临床疗效的相关性。方法：选择2016年1月—2018年12月于北京世纪坛医院口腔科就诊的150例ROU患者,同时选取同期在医院体检的健康受试者150例作为健康对照组。提取所有受试者血液DNA,采用聚合酶链反应（PCR）对IL-23R rs11465817 和 rs10489629位点基因进行扩增,对扩增产物进行酶切反应后,再做电泳,以确定基因分型。对ROU患者采用口服左旋咪唑片、维生素 C 片、维生素 B2片以及西吡氯铵漱口进行治疗。治疗前与治疗1周后采用溃疡面积和疼痛指数进行临床疗效评估。分析IL-23R rs11465817 和 rs10489629位点基因多态性与ROU易感性及临床疗效的相关性。采用SPSS 22.0软件包对数据进行统计学分析。结果：健康对照组IL-23R rs11465817和IL-23R rs10489629基因分型分布符合 Hardy-Weinberg 平衡（P>0.05）,ROU组患者IL-23R rs11465817位点CC和CA基因型分布频率显著高于健康对照组（P<0.05）。Logistic回归分析显示,携带CC、CA基因型患者ROU风险较高（P<0.05）。2组受试者IL-23R rs10489629位点基因分型频率差异无统计学意义（P>0.05）;Logistic回归分析显示,IL-23R rs10489629位点基因分型与ROU敏感性无关（P>0.05）。治疗后ROU患者平均溃疡面积和VAS评分显著降低（P<0.05）。治疗结束时,IL-23R rs11465817位点AA基因型ROU患者溃疡面积和VAS评分显著低于CC或CA基因型患者（P<0.05）。治疗结束时,IL-23R rs10489629位点各基因型ROU患者溃疡面积和VAS评分差异均无统计学意义（P>0.05）。结论：IL-23R rs11465817位点基因多态性与ROU易感性相关,可能影响ROU的临床疗效;而IL-23R rs10489629位点基因多态性与ROU易感性无关,并且对ROU疗效无显著影响。