MICA1078: A novel allele identified in a Moroccan individual affected by celiac disease

A novel MICA allele, MICA¹078, has been identified during HLA/MICA high resolution typing of Moroccan patients with celiac disease. MICA¹078 shows an uncommon variation at a highly conserved nucleotide position (nt 493, G → A), resulting in one amino acid change at codon 142 (V → I) of MICA gene (compared to MICA¹002:01), located in the α2-domain, in which V142 is the common residue.     

强直性脊柱炎患者MICA基因第2、3和4外显子的多态性及其与HLA-B抗原的连锁不平衡

目的探讨皖籍汉族人群MICA基因（major histocompatibility complex class Ⅰchain-related gene A，MICA）第2、3、4外显子的多态性，及其与HLA-B抗原的连锁不平衡在强直性脊柱炎（ankylosing spondylitis，AS）发病中的作用。方法采用聚合酶链反应-序列特异性寡核苷酸探针杂交（polymerase chain reactionsequence-specific oligonucleotide probing，PCR-SS0）技术对56例AS患者和112名正常对照人群进行MICA基因第2、3、4外显子的多态性和HLA-B抗原的检测。结果AS患者和正常对照人群的MICA等位基因分布均以MICA＊008占优势，频率分别为32．14％和30．36％。两组人群MICA＊007等位基因的分布差异有统计学意义（X^2=10．18，P〈0．05，RR=2．50）。单倍型分析显示，AS患者和正常对照人群的MICA等位基因均显示出与多个HLA-B位点的连锁不平衡现象，两组间差异有统计学意义的单倍型为MICA＊007-B27（X^2=18．46，P〈0．05，RR=7．47）。分层分析结果显示，HLA-B27阳性与AS的相关性有统计学意义（P〈0．05），但MICA＊007基因与AS的相关性无统计学意义（P〉0．05）。结论AS患者中MICA＊007等位基因频率的显著升高可能源于MICA基因与HLA-B位点间的广泛连锁不平衡。     

膜型/分泌型MICA对NK细胞受体NKG2D的相反调节效应及其对NK细胞受体谱的影响

目的　观察膜型和分泌型MICA对NK细胞受体表达的影响 ,以探讨NK细胞抗肿瘤活化机制及肿瘤细胞表达MICA分子的意义。方法　用MTT法测定人NK细胞系 (NK92 )的细胞毒活性 ;用RT PCR或FACS检测NK细胞受体 (NKG2D ,NKG2A B ,KIR2DL1,KIR2DS1)及NKG2D的识别配体MICA的表达。结果　肿瘤细胞表面的MICA分子可上调NKG2D的表达 ,下调抑制性受体NKG2A B和KIR2DL1的表达 ;而分泌型MICA (sMICA)分子对NKG2D及抑制性受体的表达均有抑制作用。结论　膜型MICA分子可上调NKG2D的表达 ,激发NK细胞对肿瘤细胞的细胞毒效应 ;分泌型MICA分子则通过降低NKG2D的表达下调机体的抗肿瘤免疫效应 ,肿瘤细胞分泌sMICA分子为肿瘤发生免疫逃逸的机制之一。     

湖南汉族人群MICA基因多态性分析

为了解湖南地区汉族人群MICA基因第2、3和4外显子多态性分布特点,采用PCR-SSP方法对162名无亲缘关系湖南汉族人群MICA等位基因进行分析。结果显示:在湖南汉族人群中共检测出12个等位基因和28种基因型,各等位基因分布频率有差异,其中以MICA*00801基因频率最高(37.9%),其次为MICA*00201/020(20.1%)和MICA*010(17.3%),频率最低的是MICA*019和MICA*031。将MICA基因在湖南汉族人群中的分布与该基因在其他人群中的分布进行比较,显示MICA基因的分布在不同人群之间存在差异,可作为中国人群的遗传标志。     

MICA的基因多态性及其临床意义

经典的主要组织相容性复合体(MHC)在排斥反应的发生、发展方面具有重要作用,但越来越多的研究表明某些非经典MHC基因在此过程中,乃至在其他疾病的免疫机制方面同样意义显著。主要组织相容性复合体Ⅰ类分子链相关基因A(major histocompatibility complex class I related chain A,MICA)即属于非经典MHC-I类基因。大量研究表明,作为最具多态性的非经典MHC-I类基因,其表达产物可借助NKG2D与自然杀伤细胞、某些特定T细胞亚群等多种免疫细胞相互作用,从而在病毒感染的免疫监视、自身免疫性疾病与器官移植排斥反应的发生发展方面均具有重要意义。     

The percutaneous learning curve of 3rd generation minimally-invasive Chevron and Akin osteotomy (MICA)

BackgroundMinimally-invasive Chevron and Akin osteotomy (MICA) represents the third-generation percutaneous hallux valgus surgery which is characterized by an extra-articular osteotomy, stable internal fixation and a high potential for correction. Compared to other percutaneous techniques of the foot, MICA is generally regarded as an advanced and demanding surgical procedure with a flat learning curve. The aim of this study is to analyze a single-surgeons experience with his first 50 consecutive MICA procedures.MethodsBetween May 2018 and February 2021, 50 consecutive MICA procedures performed by the author with the "K-wires-First technique" were prospectively analyzed focusing on surgery duration, number of fluoroscopies, correction results and surgery-associated complications. A modification of the original MICA technique as described by its inaugurators Redfern and Vernois allows the use of a standard-sized C-arm and aims to reduce revison rates and conversion to open surgery by placing the guidewires prior to performing the osteotomy.ResultsThe average surgery time for all MICA procedures was 46.8 min (SD 12.1, range 31–90 min). The average amount of fluoro shots required to perform MICA was n = 126.6 (SD 40.8, range 65–231). Comparing the preoperative and 6-week postoperative radiographs, the IMA decreased after MICA by a mean of 10.8° from 16.2° to 5.4° and the HVA by a mean of 22.1° from 30.6° to 8.5°. One case required intraoperative conversion to open hallux correction. There were 4 feet in three patients with secondary screw removal of the Chevron fixation due to prominent proximal screw tips.ConclusionsAlthough the learning curve of 3rd generation MICA is flat and requires specific training and intensive practice, the rate of complications is not elevated compared to other percutaneous hallux valgus techniques. Strict adherence to the principles of 3rd generation MICA with stable fixation and meticulous intraoperative control of each surgical step helps to reduce surgery-associated complications. The learning curve showed a continous improvement in regard to surgery time and use of fluoroscopy. After 40 procedures, the surgery time consistently dropped under 45 min and required less than 100 fluoro-shots. The modified surgical technique may help reduce Chevron screw mal-positioning when using large C-arm fluoroscopy for this procedure.     

NKG2D ligands expression patterns in gut mucosa from patients with coeliac disease

Introduction

The activating MICA/NKG2D interaction is involved in the response of intraepithelial lymphocytes (IELs) in coeliac disease (CD). The aim of this study was to investigate the expression of NKG2D ligands (MICA, MICB), IL-15 and NKG2D receptor in gut mucosa of CD patients, and the correlation with the severity of histological damage.

Patients and methods

Intestinal biopsies from 20 CD patients and five healthy controls were selected. All patients were positive for anti-transglutaminase 2 antibodies and for DQ2 or DQ8. Patients were divided into two groups according to their grade of mucosal impairment: ten each with mild and severe mucosal damage (MMD and SMD, respectively). The expression of proposed genes was determined at mRNA level. MICA expression was also determined by immunohistochemistry.

Results

Overexpression of MICA and MICB was observed in biopsies from coeliac patients compared to healthy controls (P < 0.001). Nevertheless, the expression was considerably higher in the group of patients with MMD (P < 0.0001) than in those with SMD. The levels of NKG2D receptor and IL-15 were also higher in patients than in controls, but no relationship with the severity of the mucosal lesion was found.

Conclusions

Our results suggest that NKG2D ligands may play an important role during the onset of the inflammatory process in the early stages of the development of coeliac disease.     

MICA新等位基因MICA?008：05的DNA序列鉴定及分析

目的：采用直接测序法及克隆测序法确认新等位基因 MICA?008：05。方法采用 Sequence Base Typing （ SBT）法分型技术对MICA的多态性进行常规基因分型,采用克隆测序法进行确认并与已知的等位基因序列进行比对。结果发现1个样本在外显子3上有1个碱基位置与国际通用MICA数据库不相符。该基因与MICA?008：01：01相比在外显子3的碱基位置591出现突变（ C→T）,密码子位置174由TCC→TCT,相应编码氨基酸是同义突变。结论 DNA测序结果表明该基因序列为新的MICA等位基因,已提交GenBank,并被世界卫生组织HLA因子命名委员会正式命名为MICA?008：05。