人类补体C4表型与C4A：C4B比值关系初探

用激光薄层密度扫描仪对171份血清补体 C4的电泳色带进行扫描,并求取其 C4A:C4B 比值(R 值)。结果发现含 C4A·QO 基因者的 R 值范围0.068～0.429,平均0.228,而含 C4B·QO 基因者的 R 值范围2.197～9.334,平均3.973;在所检出的7例具有 C4B·座位重复基因的样本中.其 R 值均很小(0.120～0.625),且其中含有 C4A·QO 者与不含 C4A·QO 者的 R 值有明显差异.结果表明根据 R 值大小来指定C4·QO 基因和重复基因是有一定道理的.在最常见的 C4表型3,3/1,1中,其 R 值呈常态分布,但表型3,3/2,1、3,3/2,2和3,2/1,1的 R 值多大于1.0,而表型4,4/2,2和4,4/2,1的 R 值多小于1.0。两组表型的 R 值之间的两两比较有显著性差异(P<0.01)。     

中国人不同C4基因型时血中C4浓度的定量检测

用神经氨酸酶及羧肽酶B处理血浆,依次经C4高压琼脂糖电泳、免疫固定、薄层激光扫描等步骤,并结合血浆免疫火箭电泳定量法对我国武汉地区随机人群的血浆C4总量及C4两种同种型,主要别型,单、双QO,重复座位等时的血浆C4含量进行了检测与分析。结果发现:遗传因素明显影响血浆C4水平,因而在群体中表现宽广的C4浓度范围,特别在有C4QO与C4重复基因座位时差异特别明显。这一研究提示,不同的C4基因型,循环C4含量表现明显差异。临床上检测C4含量时应该考虑患者的C4基因型别。     

中国广东地区汉族人MHC补体单倍型的分析

用国际补体参考实验室方法。首次对广东地区正常汉族家系126条染色体作了补体单倍型检测与分析。共发现18个补体单倍型,居前四位者为SC31、SC42、SC32、和SC41。其中有7个型呈连锁不平衡。4个位点等位基因分别是BF、C2、C4A、C4B。BF 以BFS;C2以C2C;C4A以C4A3和C4A4;C4B 以C482和C481频率居高。C4AQO 占4.8%,C4BQO 占1.2%,本文主要补体单倍型频率和黄、白人种接近。和日本人及东南亚地区民族接近。但和黑种人差异较大。并对地区间频率差异意义做了讨论。     

癫痫病人C4,Bf多态性检测

对103例癫痫病人的血清C4、Bf多态性进行检测,结果发现癫痫病人的Bf*F基因频率(0.1942)较正常人(0.1159)显著增高,其在该病中的病因分数(EF)和相对危险率(RR)分别为0.0885和1.8379。而C4的变化不明显。     

Graves病患者甲状腺功能与血清胱抑素C的相关性研究及其临床应用价值讨论

目的 回顾性研究正常对照人群及弥漫性毒性甲状腺肿(Graves病)患者治疗前后的甲状腺激素水平及其与血清胱抑素C水平的关系.方法 选择2013年1月至2015年9月于本院就诊的Graves病患者共185例,另选取甲状腺功能正常者24例为对照组,所有患者均行甲状腺功能(FT3、FT4、TSH)及胱抑素C(CysC)检测,并筛选其中检测后接受了碘-131治疗的患者19例,在其治疗后再次检测甲状腺功能(FT3、FT4、TSH)及胱抑素C(CysC),对比并分析结果.结果Graves病组患者胱抑素C水平明显高于对照组水平(P<0.05);Graves病组患者甲状腺激素水平与胱抑素C检测结果呈正相关,FT3、FT4与胱抑素C的相关系数分别为rs=0.69和rs=0.66(均P<0.05);Graves病患者治疗后其甲状腺激素水平与胱抑素C水平均较治疗前显著下降,两组差异具有统计学意义,治疗后与对照组比较,差异无统计学意义.结论Graves病是胱抑素C升高的重要原因;Graves病患者治疗前后胱抑素C水平与甲状腺激素水平水平呈正相关,提示在排除肾脏疾病的前提下,胱抑素C可反映甲状腺功能状态.     

汉族人MDR1 C3435T基因的多态性

目的　检测汉族人MDR1C3435T基因的分布情况。方法　应用PCR技术对正常人外周血MDR1C3435T基因进行扩增以MboI进行限制性酶切图谱分析。结果　 2 4 0例 (男 119例 ,女 12 1例 )汉族人MDR1C3435T基因中 ,表现型T/T频率是 18 75 % ,表现型T/C是 4 4 17% ,表现型C/C是 37 0 8%。MDR1C3435T基因T频率是 0 4 0 83,基因C频率是0 5 916。结论　汉族人MDR1C3435T基因的分布有自己的特点 ,为研究MDR1C3435T基因在某些疾病中的作用提供了可靠的基础资料。     

中国人C4重复基因座位初探

从78个家系266人次中研究了中国人C4基因的重复情况。在78个家系中有7个家系成员表现C4基因重复,占9.0%;依人头计,在266人中有17人C4基因表现重复,占6.4%。这17人均为C4B 基因重复,重复的类型及人数分别为,①C4B(1,2):2人,②B(1,12):6人;③B(1,1):5人;④B(1,96,96):2人;⑤B(2,2):2人。     

TRAb检测在GraVes甲亢诊断治疗中的价值

目的:探讨血清TRAb值在Graves’甲亢患者诊断治疗中的价值。方法: 50例正常人和230例Graves’甲亢患者在他巴唑治疗前后分别测定血清TRAb、FT3、FT4、TSH。结果:未经ATD治疗的Graves’甲亢患者,血清TRAb阳性率为93 3%,ATD治疗后6个月时,TRAb阳性率为41 3%,与正常对照组相比有明显差异(P<0 05),治疗6个月、12个月、36个月时TRAb阳性率分别为18 3%、8 9%、4 9%。本组临床缓解停药后有21例复发,其中TRAb持续阳性者复发18例(占80 7% )。结论:血清TRAb是诊断Graves’甲亢的主要依据,有助于判断Graves’甲亢病情进展及复发,有助于指导甲亢治疗。     

4p14区段和CTLA-4基因多态性与Graves病相关

目的探讨中国安徽蚌埠地区汉族人群4p14区段位点rs6832151和CTLA-4基因4个SNPs(单核苷酸多态性)位点基因多态性与Graves病相关性,和基因-基因交互作用对Graves病的影响。方法提取611例诊断明确的GD患者和644名健康对照者的全基因组DNA,用Taq Man探针技术进行基因分型,使用Plink和Haploview等统计软件分析这些位点与蚌埠地区汉族人群Graves病的相关性。结果 4p14区段位点rs6832151的等位基因、基因型频率在GD组和对照组之间有差异(P0.05),CTLA-4基因区域内rs231804和rs231726两个SNP位点基因型在显性模型下差异显著(P0.05);GMDR模型显示CTLA-4基因内rs10197319、rs231726、rs231804、rs1024161位点和4p14区段内rs6832151位点组成的五阶模型(P=0.001)为最佳模型,CTLA-4基因内rs1024161和rs10197319位点之间上位效应分析结果有差异(P0.05)结论 4p14区段rs6832151,CTLA-4基因区域内rs231804和rs231726位点基因多态性与蚌埠地区汉族人群Graves病的遗传易感性相关;rs6832151(4p14区段)和rs10197319、rs231726、rs231804、rs1024161(CTLA-4基因)5个SNP位点间的基因-基因交互作用与Graves病相关,CTLA-4基因内rs1024161和rs10197319位点之间存在上位效应。     

CTLA-4基因外显子4区AT重复序列多态性及碘摄入量与Graves病的相关性研究

目的 探讨细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)基因第4外显子区AT重复序列多态性多态性[CTLA-4(AT)n]及碘摄入状况与粤西汉族人Graves病(Graves disease,GD)发病的相关性.方法 收取2006年...     

C4 polymorphism in multiplex families with insulin dependent diabetes in the Tunisian population: standard C4 typing methods and RFLP analysis.

The polymorphism of C4A and C4B genes was investigated in Tunisian patients with insulin dependent diabetes (IDDM) and compared to family members (sibs) and to healthy controls. Multiplex families were analysed. A significant increase in C4AQO (26.86% vs 6.90%) and C4BQO (40.29% vs 8.28%) phenotypes was noted in IDDM patients compared with controls. Using RFLP analysis, we confirmed the high frequency of C4 null alleles. We also observed that most of these alleles were genes deleted in IDDM patients (72.23% vs 20% for CA4QO and 74.07% vs 16.70% for C4BQO). A significant decrease in the C4B long (14.92% vs 67.12%) form of the gene was also demonstrated by RFLP analysis compared with controls. Two haplotypes were frequently associated with IDDM patients in whom the C4A and C4B were deleted genes.     

Marked shortage of C4B DNA polymorphism among insulin-dependent diabetic patients

TaqI, BamHI and HinddIII polymorphisms of the C4 genes were studied with a 500-bp C4 cDNA probe (pAT-A153) specific for the 5' end of the gene. The restriction patterns obtained were correlated with the C4A and C4B genotypes in 35 patients suffering from insulin-dependent diabetes mellitus (IDDM), and results were compared to those from 40 healthy individuals. The controls, all Caucasian, were genotyped for HLA-A, B, C, DR, Bf, C2 and C4, together with 10 diabetics and their families; haplotypes for the other patients had been deduced using DNA and protein polymorphism, and taking into consideration linkage disequilibrium for neighbouring loci. No significant difference between genotypes at the C4A locus was seen in either population. The C4A gene deletion, associated with a C4B "short" gene (66.7%), was found mainly in the haplotype B8,Cw7,DR3,BfS,C2C, C4AQOB1, and the C4B gene deletion in the haplotype B18,Cw5,DR3,BfF1, C2C,C4A3BQO. When diabetic patients were compared with normal individuals, we observed, at the C4B locus, a decrease in the C4B "long" gene (22% vs. 49% respectively, p less than 0.001). A compensatory increase was observed in patients vs. controls for the frequency of C4BQO, both in the deleted and intact form (26% vs. 10% respectively, p less than 0.03).     

Multiple sclerosis: immunogenetic analyses of sib-pair double case families. II. Studies on the association of multiple sclerosis with C2, C4, BF, C3, C6, and GLO polymorphisms

The complement component polymorphisms of C2, C4, BF, C3, C6, and the enzyme polymorphism GLO were studied in 13 sib-pair double case families with multiple sclerosis. A significant association was seen between MS patients and the C4 haplotype A4,B2 as compared with their healthy siblings. This finding seems to parallel reports on C2 hypocomplementemia in MS patients since C4 A4,B2 in normal individuals was also seen to be in linkage disequilibrium with the C2 deficiency allele (C2QO) by other investigators.     

Cold urticaria associated with C4 deficiency and elevated IgM

Various immunologic abnormalities have been implicated in cold urticaria. This is the first report of cold urticaria associated with C4 deficiency and elevated IgM. A 12-year-old male developed urticaria upon exposure to cold. He denied fever, purpura, hemoglobinuria, Raynaud's disease, or arthralgias. Family history was negative for cold urticaria. Immunologic studies revealed elevated IgM (186 mg/dL) as well as decreased CH100 and C4 (8.0 mg/dL). C1, C2, and C3 were normal. Ice cube skin test was positive, but passive transfer tests were negative. Biopsy was not diagnostic for vasculitis, although it revealed a few immunofluorescent deposits of IgM and C4. Complement genetic studies revealed deficiency of two half-null C4 haplotypes expressed as C4A*3QO and B*2QO.     

Polymorphism of C4 and factor B in type I diabetes

The haplotypic frequencies of the fourth component of complement (C4) and factor B (Bf) have been determined in 44 Alsatian type 1 diabetics. An increased frequency of the rare allele Bf F1 (9.1% vs 1.5%) and of the silent alleles of C4 (C4 AQO: 21.6% vers 15.5% -C4 BQO: 29.6% vs 16.0%) was observed in diabetics in comparison to the general population of the same geographic area. A complete HLA haplotype determination has been obtained in 24 type 1 French diabetics. Three haplotypes were associated with the diabetic susceptibility: HLA-A30 CW5 B18 BfF1 C4A3BQO DR3 (18.75% vs 0.86%), HLA-A1 CW7 B8 BfS C4AQOB1 DR3 (15.58% vs 4.17%), HLA-A2 CW3 BW62 BfS C4A3B3 DR4 (6.25% vs 0.45%). The authors suggest that the silent alleles of C4 could modulate the expression of the diabetic susceptibility genes by lowering of the serum C4 hemolytic activity.     

HLA and C4 in subacute sclerosing panencephalitis

The frequencies of HLA-A, B, C, DR and DQ antigens were studied in 63 Japanese patients with subacute sclerosing panencephalitis (SSPE). The results could not confirm the statistical association between SSPE and HLA antigens. In addition, the allele frequencies of complement components C4, C2 and BF were determined in the 20 haplotypes with 10 unrelated SSPE patients. A significant association of C4A QO with SSPE in Caucasians was not found in Japanese.     

中国广东地区汉族人群补体C4单倍型分析

采用改良的国际补体参考实验室方法,检测广东地区汉族人群补体C4单倍型。在156条无关染色体中,共检出14种C4单倍型:A3B1频率最高(0.3269),A3B2(0.2436)和A4B2(0.1090)次之,以下依次为A4B1(0.0705);AQ0B2和AQ0B1(均为0.0641);A2B1(0.0321);A3BQ0(0.0256);A3B5和A3B4(均为0.0192);A5B4、AQ0B4、AQ0B96和AQ0BQ0频率最低(均为0.0064)。其中A4B2和A2B1呈正向连锁不平衡。将广东汉族与其它不同种族群体的数据进行比较,发现广东汉族C4单倍型分布具有明显特点。     

Immunogenetic markers (BF, C2, C4, 21-OH, TNF alpha, TCR beta, Ig) and insulin-dependent diabetes in the Tunisian population: serological and molecular study]

48 Tunisian people suffering from the IDDM auto-immune disease were compared to 35 control healthy persons for the polymorphisms of the complement BF, C2 and C4 proteins and genes, of the IgG (Gm allotypes) as well as of the TNF alpha and TCR C beta genes. Our study shows that the BFF1-C4A3-C4BQO and BFS-C4AQ0-C4B1 complotypes are associated to IDDM (RR of 2.97 and 3.07 respectively), as previously reported for other circummediterranean populations. The frequency of the Gm 21.28; 1.17; .. haplotype is increased, but not significantly, among the patients. The RFLP analysis reveals that the 2.65 kb SacI allelic restriction fragment of the C2 gene may be considered as a genetic marker of susceptibility to IDDM because its frequency raises to 0.206 among the patients vs 0.021 in the healthy individuals (p less than 0.001). The frequencies of the C4AQ0 and C4BQ0 alleles are more important among the IDDM patients than within the control sample, but the only C4BQ0 allele frequency is significantly increased. Both C4AQ0 and C4BQO result mainly from deletions. The frequencies of the allelic restriction fragments of the TNF alpha and TCRC beta genes are not significantly different among the patients and the controls. But the small sample size don't allow us to conclude definitively. It would be very interesting to extend the RFLP analysis to the TCR V beta and V alpha gene regions on more numerous samples.     

HLA-DR4 associated Dw types in rheumatoid arthritis

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)