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.     

Comparative Study of Clinical Effects Between Plasma Adsorption and Double Filtration Plasmapheresis in Patients with Myasthenia Gravis

Abstract: Plasma exchange (PE) has been one of the most powerful treatments for patients with myasthenia gravis (MG) since Pinching et al. reported its clinical usefulness in 1976, despite the need for supplemental human plasma. However, new apheresis techniques, e.g., plasma adsorption (PA) and double filtration plasmapheresis (DFPP), which do not need human plasma, were developed and have been introduced for clinical use in MG. We compared the effects of these plasma purification therapies in patients with MG and found that DFPP improved such subjective symptoms as chest compression and general fatigue better than PA while both of them could decrease the serum level of acetylcholine receptor (AChR) antibodies and relieve objective muscle weakness to a similar degree. It may be that DFPP can remove some circulating pathogenic factors other than AChR antibodies more efficiently than PA.—     

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.     

Myasthenia Gravis and Lambert‐Eaton Syndrome

Abstract: Myasthenia gravis is a common autoimmune disorder characterized by the presence of pathogenic antibodies directed against the acetylcholine receptor. Patients present with variable degrees and distribution of fluctuating weakness at times life threatening. Clinical manifestations, establishment of diagnosis, the natural history of myasthenia gravis, and therapeutic options are herein reviewed. Far less common is Lambert‐Eaton syndrome (the myasthenic syndrome), another autoimmune disorder due to the presence of antibodies directed against the PQ‐type voltage‐gated calcium channels. Clinical features and treatment options are summarized.     

Plasma Exchange for Treatment of Myasthenia Gravis: Pathophysiologic Basis and Clinical Experience

Abstract: Myasthenia gravis is an autoimmune disease characterized by production of antibodies to acetylcholine receptors located at the motor end plate in skeletal muscles. The antibodies bind and subsequently induce degeneration of these receptors. Loss of acetylcholine receptors results in inadequate contraction of muscle fibers in response to acetylcholine released from nerve terminals and clinically apparent muscle weakness. Plasma exchange removes the circulating antibodies in myasthenic patients with short‐term clinical improvement. Plasma exchange may be indicated in patients with acute exacerbation of neuromuscular weakness with bulbar or respiratory compromise, preoperative optimization prior to thymectomy, and postoperative deterioration following thymectomy or other surgical procedures. Long‐term, intermittent plasma exchange for patients who do not adequately respond to standard treatment is another evolving indication.     

Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1 *15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1, DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1 *15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1 *01, DQB1 *05 and HLA-DQA1 *01,DQB1 *06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.     

Sequential Plasmapheresis and Intravenous Immunoglobulin Therapy for Refractory Myasthenia Gravis: Case Report

Immunotherapy is currently the standard therapy for myasthenia gravis (MG) although some patients may be refractory to treatment. We describe the use of sequential plasmapheresis and intravenous immunoglobulin (IVIG) therapy for treatment of advanced MG in a patient refractory to all forms of medical treatment including corticosteroids, immunosuppressants, and intermittent plasmapheresis. The patient, a 37-year-old woman with systemic lupus erythematosus (SLE), had initially responded well to treatment with high dose corticosteroids and intermittent plasmapheresis, with the duration of response ranging from 3 to 4 months. However, after 18 months of therapy, the duration of response had gradually decreased to 1 month. She responded well to a 5 day trial of plasmapheresis followed by high dose IVIG, and the duration of response increased to 6 months. The SLE activity was relatively silent during each relapse. This report indicates the potential usefulness of sequential plasmapheresis and IVIG in the treatment of patients with refractory MG and SLE.     

Association of Smoking and Generalized Manifestations of Myasthenia Gravis

Objective Smoking is a known risk factor for the development and progression of autoimmune diseases. Previous studies in ocular myasthenia gravis (MG) patients showed that smoking is associated with the severity of symptoms and progression to generalized MG. However, whether smoking affects MG symptoms in patients with a broader clinical spectrum of presentations is unknown. Therefore, in this study, the associations of smoking with the clinical characteristics of MG were analyzed in a cohort of patients including those with generalized, seronegative, and thymoma-associated MG. Methods The smoking history was investigated in a cross-sectional study of 187 patients with MG followed in a referral hospital for neurology. The association of smoking with MG-activities of daily living score at survey, the presence of generalized manifestations, and the age of onset was assessed using multiple regression models. Results Neither current nor prior smoking habit was associated with the MG-activities of daily living score at survey. However, smoking exposure after MG onset was significantly associated with the presence of generalized manifestations during the disease course (odds ratio, 3.57; 95% confidence interval, 1.04, 12.3). The smoking history before or at onset of MG was not associated with the age of onset. Conclusion Smoking exposure after the onset is associated with generalized manifestations of MG in our cohort of patients with a broad clinical spectrum of presentations.     

HLA-DQA1基因与广西地区壮族、汉族2型糖尿病关联性研究

目的　研究HLA DQA1基因与广西地区壮族、汉族 2型糖尿病 (DM )的关联。方法　采用聚合酶链反应 序列特异性引物 (PCR SSP)技术 ,分别对广西 67例壮族和 72例汉族 2型DM及 69例壮族、65例汉族正常对照的HLA DQA1位点进行基因分型。结果　壮族 2型DM组DQA1 0 3 0 1、DQA1 0 40 1等位基因频率显著高于壮族对照组 (P <0 .0 0 1,RR =4.69和P <0 .0 0 1,RR =7.5 5 ) ,汉族 2型DM组DQA1 0 10 4等位基因频率明显高于正常汉族对照组 (P =0 .0 0 1,RR =6.5 1) ;DQA1 0 60 1在壮族 2型DM组明显低于对照组 (P <0 .0 0 1,RR =0 .14 ) ,DQA1 0 40 1等位基因频率在汉族 2型DM组明显低于汉族对照组 (P <0 .0 0 1,RR =0 .2 9)。结论　DQA1 0 40 1、DQA1 0 3 0 1可能是广西壮族 2型DM的易感基因 ,而DQA1 0 10 4可能为汉族 2型DM的易感基因 ;DQA1 0 60 1可能是壮族 2型DM的保护基因 ,DQA1 0 40 1则可能是汉族 2型DM的保护基因     

Pancreatic Cancer in a Patient with Myasthenia Gravis

Myasthenia gravis has been associated with several diseasessuch as hyperthyroidism and malignancy (thymoma,lung carcinoma) but so far no reports have demonstrated arelationship between this disease and pancreatic disease.We report a 66-year-old man with myasthenia gravis diagnosedon the basis of clinical symptoms (eyelid ptosis),typical abnormalities on repetitive nerve-stimulation tests,and the presence of Ach-R antibodies in the serum. The responseto anticholinesterasic agents (pyridostigmine) wasgood, but after 1 year, he developed pancreatic cancer andmyasthenia gravis symptoms recurred. After surgery andchemotherapy, myasthenia gravis symptoms disappeared.Some months later, the patient had a recurrence of pancreaticcancer after relapse of myasthenia gravis.     

HLA-DQA1*1 contributes to resistance and A1*3 confers susceptibility to Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects

Summary In this study HLA-DQA1 and TNF genes in addition to HLA-DQB1 gene were investigated at DNA level for elucidation of the genetic backgrounds of Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects. DNA, amplified by polymerase chain reaction, was subjected to allele specific oligonucleotide dot blot analysis, restriction fragment length polymorphism analysis or DNA sequencing. Polymorphism of the TNF gene to NcoI did not correlate with Type 1 diabetes in Japanese patients. DQw1.2 had a protective effect against the disease, the DQA1^*1 allele was significantly decreased and DQA1^*3 allele was significantly increased. Seventeen out of twenty-two Type 1 diabetic patients (77%) were homozygous for DQA1^*3 and five out of twenty-two (23%) heterozygous. The DQA1^*3 gene of Type 1 diabetic patients had a normal nucleotide sequence. Furthermore, DQA1^*3 was found unexpectedly in two patients without DR4 or DR9. These data indicate that DQA1 gene confers susceptibility and resistance to Type 1 diabetes in Japanese subjects.     

Immunoadsorption in Myasthenia Gravis Based on Specific Ligands Mimicking the Immunogenic Sites of the Acetylcholine Receptor

Abstract: A specific system for antibody removal from blood circulation in myasthenia gravis (MG) patients was devised by use of the immunoadsorbent bound to an acetylcholine receptor (AChR) peptide that was synthesized corresponding to the sequence of residues 183‐200 of the AChR alpha‐subunit (alpha 183‐200), antibodies which prevent the binding of ACh to AChR. The alpha 183‐200 peptide was confirmed to be immunogenic for induction of an animal model of the disease and for reactivity with MG autoantibodies. We then made use of these results for immunoadsorption therapy through the antigen‐antibody reaction on the molecular level, having given patients relief from myasthenic weakness. The greatest care was taken for the selection of an antigenic region in the molecular structure among various myasthenogenic domains of AChR and for the antigenic conformation of synthetic peptide as the adsorbent to react with antibodies raised against the native protein.     

The Six Year Experience of Plasmapheresis in Patients with Myasthenia Gravis

Abstract: Plasmapheresis (PP) effectively removes autoantibodies in various autoimmune diseases. The use of PP in the treatment of myasthenia gravis (MG) has been widely accepted since the 1970s. The treatment protocol, however, has not been standardized. For the last 6 years, we collected a total of 94 MG patients, 38 males and 56 females aged 14–80 years, who received 175 courses of PP treatment for a total of 823 sessions. The methods we used were double filtration plasmapheresis (DF), immunoadsorption plasmapheresis (IA), and plasma exchange (PE). There were 167 courses of DF, 6 courses of IA, and 2 courses of PE. Each course of treatment consists of 4 to 5 sessions of apheresis. The processed volume of plasma is 1 calculated plasma volume. All patients tolerated PP well although 2.3% of them experienced hypotension. Our experiences are summarized as follows. Both DF and IA effectively ameliorate symptoms and signs of MG. IA removes acetylcholine receptor antibody more effectively than DF does, but clinical effects between these 2 methods are similar. A daily schedule seems more effective than an alternate daily schedule. The optimal number of PP sessions for each course is 4. The factors correlating with better clinical response are high MG score, nonthymoma patients, younger age at onset, and higher removal rate for immunoglobulin G.     

Specific Immunoadsorbent for Myasthenia Gravis Treatment: Development of Synthetic Peptide Designed to Remove Antiacetylcholine Receptor Antibody

Abstract: We have developed Medisorba MG, a new immunoadsorbent column for myasthenia gravis (MG). The a 183–200 segment of the Torpedo Californica acetylcholine receptor (AChR) is recognized as the acetylcholine binding site by the blocking antibody, which is one of the anti-AChR antibodies involved in the pathogenesis of MG. As a specific affinity ligand to remove the blocking antibody, Torpedoα 183–200 was synthesized and immobilized covalently to porous cellulose beads. This immunoadsorbent showed specific removal of the blocking antibody without reducing IgG and albumin levels significantly in clinical evaluation and in vitro study. Clinical improvement was found in 78% of the cases, and no adverse effects were observed in any case. The Medisorba MG column has been confirmed as a useful device for the treatment of MG.     

Removal Characteristics of Immunoadsorption with the Tryptophan‐Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis

Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan‐immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan‐immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were performed (five sessions of IA and 14 sessions of SeIA) when the processed plasma volume was 2 L. The corresponding reductions were 52.5% ± 6.2% for AChRAb, 58.8% ± 4.2% for fibrinogen, and 36.9% ± 5.5% for FXIII after one session of IA. The corresponding reductions were 45.2% ± 9.9% for AChRAb, 3.5% ± 6.9% for fibrinogen, and ?4.6% ± 11.1% for FXIII after one session of SeIA. The removal rates for AChRAb, fibrinogen, and FXIII in IA were significantly higher than those in SeIA. IA could effectively remove AChRAb, and SeIA could retain fibrinogen and FXIII. IA can be combined with SeIA, resulting in both IgG autoantibodies removal by IA and retention of coagulation factors by SeIA.     

云南汉族原发性高血压左室重构与HLA-DQAl等位基因的相关研究

目的探讨云南汉族原发性高血压(EH)左室重构包括左室肥厚(LVH)及左室扩大(LVD)与HLA-DQA1等位基因的相关性。方法对超声心动图诊断的云南汉族中43例高血压合并LVH患者(EH-LVH 组)与48例高血压非LVH患者(EH-LVH-组)、对16例高血压伴左室扩大患者(EH-LVD 组)与75例高血压不伴左室扩大患者(EH-LVD-组)分别进行病例-对照研究,采用PCR- SSP技术对其进行HLA-DQA1等位基因分型。结果(1)EH-LVH 组中DQA1*0302频率明显高于EH-LVH-组(18.8%vs 5.8%,χ~2=6.876,P<0.01;RR=3.73);EH-LVH 组中DQA1*0201频率明显低于EH-LVH-组(5.2%vs 24.4%,χ~2=13.671,P<0.01;RR=0.17);(2)HLA-DQA1等位基因频率在EH-LVD 组与EH-LVD-组的比较无统计学意义(P>0.05);(3)原发性高血压伴左室肥厚的易患因素是:病程、收缩压、DQA1*0302。结论云南汉族HLA-DQA1等位基因可能与高血压病左室重构中的心肌肥厚有关而与心腔扩大无明显相关。DQA1*0302可能是云南汉族EH-LVH的易感基因;DQA1*0201可能是EH-LVH的保护基因。病程长、收缩压高是原发性高血压伴左室肥厚的易患因素。     

Therapeutic Apheresis in Myasthenia Gravis Patients: A Six Year Follow-Up

Abstract: Six years ago 4 patients suffering from myasthenia gravis (MG) types C and E according to Compston with failed drug therapy were initially treated 3 times (1 patient, a total of 11 times) by protein A immunoadsorption (Immunosorba, Excorim AB, Lund, Sweden). No further immunoadsorption treatments have been carried out. In addition, 3 patients were given a thymectomy. The present status of the patients was checked. We could see a beneficial effect in all MG patients. The patients are fit for work; each has an improved Besinger index. The patients were used as their own controls. A higher anti-AChRAb level 6 years after protein A immunoadsorption than at the beginning was seen in all patients, combined with less serious MG. In addition, their immunomodulation could be induced as seen in lymphocyte and inflammatory protein changes during the first 36 days after beginning immunoadsorption treatment. A larger population has to be investigated to verify these results.     

51例重症肌无力患者的临床与胸腺病理和电镜分析

目的分析胸腺增生与伴胸腺瘤的重症肌无力患者临床表现及其胸腺病理类型和超微结构特点。方法对51例MG患者的病例资料进行回顾性分析。按照胸腺瘤组和胸腺增生组,对临床症状、MG危象发生率、胸腺瘤WHO组织学分型、胸腺超微结构特点等各项指标进行对比。结果胸腺瘤组临床症状重、MG危象发生率高、术后MG症状改善程度差。结论胸腺瘤组MG患者病情重,WHO组织学分型对于区别良恶性肿瘤及预后有指导意义,胸腺超微结构特点的研究有助于澄清MG的发病机制。