Diagnostic and classification criteria of Takayasu arteritis

Takayasu arteritis (TA) is a chronic large vessel vasculitis that affects aorta, its main branches and pulmonary arteries. The inflammatory process results in stenosis, occlusion, dilation or aneurysm formation in the arterial wall. TA has been described in different parts of the world and affects predominantly young individuals (<50 years of age). Patients with TA may present constitutional symptoms, vascular pain (e.g. carotidynia) and typical features such as limb claudication, decreased or absent peripheral pulses, vascular bruits, hypertension, and reduction or discrepancies in blood pressure between arms. A proper diagnosis of TA is an important issue since delays may result in significant morbidity. The definition of TA was included in the 1994 and 2012 Chapel Hill Consensus Conference and TA was categorized as a large vessel vasculitis. The first diagnostic criteria for TA were developed by Ishikawa in 1988 and modified by Sharma et al., in 1995. Two sets of classification criteria were developed for TA to include patients in epidemiologic studies and clinical trials: the 1990 ACR Classification Criteria for TA and the Classification Criteria for childhood TA proposed by the European League Against Rheumatism (EULAR), the Pediatric Rheumatology European Society (PRES) and by the Pediatric Rheumatology International Trials Organization (PRINTO) to be used for patients younger than 18 years. The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an international effort that is under way to develop a single classification system and a validated set of diagnostic criteria for systemic vasculitides using data-driven methods.     

HLA-DQA1, DQB1 and DRB1 alleles associated with Takayasu arteritis in the Chinese Han population

Takayasu arteritis (TA) is a chronic large-vessel vasculitis of unknown etiology. Human leukocyte antigen (HLA) alleles play an important role in the development of TA. Sequence specific primer-polymerase chain reaction was used to detect 10 alleles of the HLA-DQA1 gene and 13 alleles of the HLA-DQB1, -DRB1 gene. A significant increase in the frequencies of DRB1¹07 (Pc < 0.01, OR = 3.44, CI: 2.15–5.52) was observed among TA patients compared with the control group. The significantly increased frequencies of the haplotype DQA1¹03:01-DQB1¹03:01-DRB1¹07 (Corrected P-values < 0.01) were observed in TA patients. But in the analysis of clinical manifestations, there are no significant associations with the HLA-DRB1¹07 allele.     

Unilateral pleural effusion secondary to Takayasu arteritis: a case report and literature review

Takayasu arteritis (TA) is a chronic, nonspecific inflammatory disease of large and medium-sized vessels that primarily involves the aorta and its branches. TA involving the pulmonary arteries has a prevalence ranging from 14% to 86%, which can lead to pulmonary hypertension, a progressive increase in pulmonary artery pressure, and eventually death from right heart failure. The presentation of pulmonary arteritis (PA) is very nonspecific, with a reported misdiagnosis rate of up to 60% and a diagnosis time ranging from 1 month to more than 10 years. The clinical manifestation of pleural effusion is very rare in both TA and PA cases. Based on our literature review, this is the 6^th reported case of TA with pleural effusion, and the specific mechanism of TA with pleural effusion is still unclear. The characteristics of this case and the previously reported cases are summarized in this article to improve the understanding of TA and PA and reduce the misdiagnosis rate.     

A case of 37 year long Behçet disease resembling Takayasu arteritis: An autopsy report

A 19‐year‐old woman with a history of recurrent aphthous stomatitis and genital ulceration was diagnosed with Behçet disease. She was treated with steroids and immunosuppressive agents for more than 30 years, but multiple complications manifested including ileocecal ulcer, aortic valve regurgitation, renal failure, ischemic enterocolitis, and arteriosclerotic obliterans until her death at the age of 56 from pneumonia. An autopsy examination demonstrated an entirely calcified aorta and major aortic branches. The ascending aorta was dilatated 55 mm in diameter and branches were all stenosed. Microscopically, the aortic arch and its branches showed collagenous fibrosis of the outer media and adventitia, whereas coronary and abdominal aortic branches showed conventional atherosclerosis. Although the ante‐mortem diagnosis was angio‐Behçet disease, its pathophysiology along with her clinical history, morphology of the lead pipe‐like aorta, predominant destruction of the outer arteries, and a human leukocyte antigen (HLA) haplotype of B39 were all suggestive of Takayasu arteritis. Thus, this case implies that HLA‐B39 may be associated with the pathogenesis of arteritis like Takayasu arteritis, even if the primary disease is Behçet disease.     

Association of susceptibility to Takayasu arteritis in Chinese Han patients with HLA-DPB1

Takayasu arteritis (TA) is a chronic large-vessel vasculitis of unknown etiology. Human leukocyte antigen (HLA) alleles play an important role in the development of TA. The association between HLA-DPB1 and TA in Chinese Han patients remains unclear. We examined the genotypes of 72 Chinese patients with TA and 180 healthy unrelated individuals who did not have any history of chronic disease. HLA-DPB1 genotypes were determined using polymerase chain reaction sequence-specific primer (PCR-SSP). The frequencies of DPB1*09 and DPB1*1701 among the TA patients were significant higher than among the controls. The mean age of the onset of TA in patients with DPB1*1701 alleles was significant earlier than the DPB1*1701 negative patients. Our results indicated that the HLA-DPB1*09 and DPB1*1701 alleles might increase the susceptibility to TA, and the individuals possessing DPB1*1701 had the earlier onset age of the disease. Further studies on the mechanism underlying are warranted.     

Resveratrol improves treatment outcome and laboratory parameters in patients with Takayasu arteritis: A randomized double-blind and placebo-controlled trial

Tumor necrosis factor (TNF) inhibitors have exhibited certain clinical efficacy in treating refractory Takayasu arteritis (TA), albeit with severe adverse effects. We aimed to explore the anti-TNF function of resveratrol, a natural compound, in the treatment of TA. A total of 271 patients diagnosed of acute TA were enrolled in this clinical trial, who were then randomized to be administered 250 mg resveratrol or placebo on a daily basis for a period of 3 months, and revisited biweekly to assess treatment outcomes. Primary treatment outcome was defined as the disease activity, determined using the Birmingham Vascular Activity Score (BVAS). Secondary outcome was defined by laboratory parameters, including erythrocyte sedimentation rate (ESR), plasma levels of C-reactive protein (CRP) and TNF-α. BVAS score and laboratory parameters of patients receiving resveratrol treatment exhibited a steady decline throughout the study. In contrast, outcomes remained practically unchanged in placebo-treated patients. Strong linear correlations were also observed between TNF-α with BVAS scores, ESR and plasma levels of CRP. Resveratrol could greatly improve treatment outcome and laboratory parameters in acute TA patients, likely due to its anti-TNF property.     

Takayasu Arteritis: Diagnosis,Treatment and Prognosis

Takayasu arteritis (TA) is a chronic nonspecific granulomatous vasculitis affecting aorta and its main branches, coronary and pulmonary arteries. TA often occurs in young women and has a characteristic heterogeneity depending on ethnicity and geographical location. Although the pathogenesis of TA remains unclear, the interaction of many factors, such as autoimmunity, inflammation, genetic and environmental factors and so on, is involved in the occurrence and development of TA. Angiography, which is recognized as the gold standard in evaluating vascular lesions in TA, combined with computer tomography angiography (CTA), magnetic resonance angiography (MRA), ultrasonography, ¹⁸Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) could not only provide important information for early diagnosis but also detect disease activity, and thus further guide the treatment in TA. In addition, beside the commonly used corticosteroids, immunosuppressive agents, percutaneous transluminal angioplasty (PTA) and surgical revascularization, anti-tumor necrosis factor (TNF) agent has been more widely used in refractory cases of TA. The objective of this review is to systemically describe the pathogenesis, clinical characteristics, diagnosis, treatment and prognosis of TA.     

Associations between clinical features and therapy with macrophage subpopulations and T cells in inflammatory lesions in the aorta from patients with Takayasu arteritis

Takayasu arteritis (TAK) is a large-vessel granulomatous vasculitis; the inflammatory infiltration in arteries comprises macrophages, multi-nucleated giant cells, CD4⁺ and CD8⁺ T cells, γδ T cells, natural killer (NK) cells and neutrophils. However, it is unknown which subtype of macrophages predominates. This study aims to evaluate macrophages subpopulations in the aorta in TAK. Immunohistochemistry was performed in the aorta from TAK patients (n = 22), patients with atherosclerotic disease (n = 9) and heart transplant donors (n = 8) using the markers CD68, CD86, CD206, CD3, CD20 and CD56. Active disease was observed in 54·5% of patients and active histological lesions were found in 40·9%. TAK patients presented atherosclerotic lesions in 27·3% of cases. The frequency of macrophages, M1 macrophages, T, B and NK cells was higher in the aorta from TAK and atherosclerotic patients compared to heart transplant donors. In TAK, macrophages and T cells were the most abundant cells in the aorta, and the expression of CD206 was higher than CD86 (P = 0·0007). No associations were found between the expression of cell markers and active disease or with atherosclerotic lesions. In TAK patients, histological disease activity led to higher T cell counts than chronic fibrotic lesions (P = 0.030), whereas prednisone use was associated with lower T cell counts (P = 0·035). In conclusion, M1 macrophages were more frequent in TAK and atherosclerotic patients compared to heart transplant donors, while M2 macrophages dominated M1 macrophages in TAK. T cells were associated with histological disease activity and with prednisone use in TAK.     

Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis

Objectives

To assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population.

Tocilizumab and refractory Takayasu disease: Four case reports and systematic review

Background

Relapses upon corticosteroids tapering and immunosuppressive agents are frequent in Takayasu arteritis (TA). Interleukin-6 is highly involved in physiopathology of TA. Many reports showed efficacy of tocilizumab (TCZ) in refractory TA cases. We report four cases and an updated literature review on the TCZ efficacy and safety in patients with TA.

Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci

The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia. Distributions of genotypes at all loci and in all populations fit Hardy-Weinberg equilibrium expectations. There was not a single allele predominant at any of the loci in these populations, with the exception of A*3002 [allele frequency (AF) = 0.233] in Zambians and Cw*1601 (AF = 0.283) in Malians. This distribution was consistent with balancing selection for all class I loci in all populations, which was evidenced by the homozygosity F statistic that was less than that expected under neutrality. Only in the A locus in Zambians and the C locus in Malians, the AF distribution was very close to neutrality expectations. There were six instances in which there were significant deviations of allele distributions from neutrality in the direction of balancing selection. All allelic lineages from each of the class I loci were found in all the African populations. Several alleles of these loci have intermediate frequencies (AF = 0.020-0.150) and seem to appear only in the African populations. Most of these alleles are widely distributed in the African continent and their origin may predate the separation of linguistic groups. In contrast to native American and other populations, the African populations do not seem to show extensive allelic diversification within lineages, with the exception of the groups of alleles A*02, A*30, B*57, and B*58. The alleles of human leukocyte antigen (HLA)-B are in strong linkage disequilibrium (LD) with alleles of the C locus, and the sets of B/C haplotypes are found in several populations. The associations between A alleles with C-blocks are weaker, and only a few A/B/C haplotypes (A*0201-B*4501-Cw*1601; A*2301-B*1503-Cw*0202; A*7401-B* 1503-Cw*0202; A*2902-B*4201-Cw*1701; A*3001-B*4201-Cw*1701; and A*3601-B*5301-Cw*0401) are found in multiple populations with intermediate frequencies [haplotype frequency (HF) = 0.010-0.100]. The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci. Comparison of the genetic distances measured by the distribution of alleles at the HLA class I loci in the sub-Saharan populations included in this and other studies indicate that the Luo population from western Kenya has the closest distance with virtually all sub-Saharan population so far studied for HLA-A, a finding consistent with the putative origin of modern humans in East Africa. In all African populations, the genetic distances between each other are greater than those observed between European populations. The remarkable current allelic and haplotypic diversity in the HLA system as well as their variable distribution in different sub-Saharan populations is probably the result of evolutionary forces and environments that have acted on each individual population or in their ancestors. In this regard, the genetic diversity of the HLA system in African populations poses practical challenges for the design of T-cell vaccines and for the transplantation medical community to find HLA-matched unrelated donors for patients in need of an allogeneic transplant.     

Human T-cell lymphotropic virus type I in Iranian-born Mashhadi Jews: Genetic and phylogenetic evidence for common source of infection

High prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection and disease has been identified among Iranian-born Mashhadi Jews, an ethnically segregated, highly inbred population. To determine the origin and genetic diversity of HTLV-I in this group, 1,039 bp spanning selected regions of the HTLV-I gag, pol, env and pX genes were enzymatically amplified and sequenced directly from DMA of five Mashhadi Jews (three with spastic myelopathy and two asymptomatic carriers). Alignment and comparison of these sequences with cosmopolitan and Australo-Melanesian topotypes of HTLV-I indicated that the HTLV-I strains from Mashhadi Jews, which were ?99.9% identical among themselves, exhibited considerable sequence similarity (?99%) to HTLV-I strains from southern India, suggesting a common source of infection. Phylogenetic analysis, using the maximum parsimony method, was consistent with a single-source introduction of HTLV-I into the Mashhadi Jewish community. © 1995 Wiley-Liss, Inc.     

A description of a new DR allele, DRB1*1113

Abstract: We have discovered a previously unpublished HLA-DRB1 allele, observed in a patient (SB), his mother, and one sibling. The undefined allele gave sporadic positive reactions with sera in the DR52-associated group. SSOPH analysis utilizing both generic and group specific primers and probes also gave ambiguous results. SB typed clearly as a DRB 1*0301 (paternal allele) but the DNA from SB also bound probes specific for DRB 1*14 and DRB1*11. Sequencing revealed that the undefined allele was similar to a DRB 1*14 allele with a segment of sequence found in DRB1*11 alleles. The patient was MLC reactive with donors who express DRB1*0301, *1401 and *0301, *11 and was nonreactive solely to DRB 1*0301 (Dw3) homozygous typing cells.     

Investigation of killer cell immunoglobulin-like receptor (KIR) gene diversity: KIR2DL2, KIR2DL5 and KIR2DS5

Human killer cell immunoglobulin-like receptor (KIR) genes are important for restraining natural killer cytotoxicity toward cells with autologous human leukocyte antigen (HLA) while targeting cells lacking or expressing low levels of self-HLA molecules. KIR gene content and alleles vary across individual genomes and populations, requiring specialized laboratory tools for their characterization. Here, we detail methods based on sequence-specific polymerase chain reaction amplification and oligonucleotide probe hybridization to identify alleles of KIR2DL2, KIR2DL5A, KIR2DL5B and KIR2DS5. Allele frequencies for a Northern Irish population of 354 individuals typed with this system are given, along with results from 132 cell lines from the International Histocompatibility Workshop that cover many world populations. This information complements published reports by our laboratory for allele-level typing of other KIR members, totaling 12 of the 17 known genes. These methods are allowing us to characterize KIR haplotypes in our population.     

Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan.

Hepatitis C viral infection in 125 hemodialysis patients from Taiwan was studied using a second-generation anti-HCV immunoassay (EIA II) (Abbott HCV 2.0 EIA) and the polymerase chain reaction (PCR) to detect the HCV RNA in the serum. A total of 59 patients (47.2%) were positive by EIA II. In comparison, the conventional C100-3 anti-HCV assay was positive in 40 (32.0%). HCV RNA was found in 47 patients (37.6%). Patients with elevated serum transaminase level had a higher positive rate of anti-HCV and HCV RNA. The dialysis time was longer for those patients positive for anti-HCV than for those who were negative. A total of 57 of the 59 EIA II-positive cases had a history of blood transfusion. The HBsAg status did not influence the anti-HCV positivity. Among the 59 EIA II-positive patients, 66.1% were also positive for HCV RNA, and of the 47 HCV RNA-positive cases 83.0% were positive for EIA II. It is concluded that the high prevalence of specific HCV infection and HCV viremia was present in these patients. Prevention of cross-contamination during dialysis and blood screening before transfusion are important for the control of HCV infection in these patients.     

HLA—DQB1＊0301与胃腺癌及幽门螺杆菌感染的关系

为探讨HLA－DQB1等位基因与胃腺癌临床特征及其幽门螺杆菌（Hp)感染的关联性，运用序列特异性引物聚合酶链反应技术，检测无亲缘关系湖北汉族健康人136例，胃癌组63例患者的HLA－DQB1基因，内镜活检，Giemsa染色和（或）外周血ELISA检查胃粘膜Hp感染情况，SAS软件编译处理，结果表明HLA－DQB1基因，内镜活检，Giemsa染色和（或）外周血ELISA检查胃粘膜Hp感染情况，SAS软件统计处理。结果表明HLA－DQB1*0301与湖北汉族人胃腺癌呈正关闻。携带与非带该等位基因患者，。其临床特征包括患者平均患病年龄，性别比，肿瘤原发部位，肿瘤TNM分期，肿瘤细胞分化程度，以及Hp感染率等情况比较，均无显著差别，HLA－DQB＊0301等位基因并不是通过增加Hp感染危险性，而影响胃腺癌的遗传易感性。     

中国南北地区两个人群HLA-A座位DNA分型的比较研究

目的对我国北京和广州的各一个群体进行ＨＬＡ－Ａ座位分型并进行比较研究。方法用ＰＣＲ／ＳＳＯＰ的ＤＮＡ基因分型方法,使用引物１对,探针５４种。用同位素磷３２标记探针进行ＤＮＡ杂交,用Ｘ片曝光判断结果。结果共检出ＨＬＡ－Ａ基因１８种,南北人群有一定程度的差异,表现在北方北京地区人群中Ａ＊０２０５、０２１０和Ａ＊２９０１未检出,Ａ＊２６０１、３００１和３１０１等基因高于南方广州人群;而南方广州群体中Ａ＊３１０１、３２０１和６８０１未检出,Ａ＊０２０３、１１０１高于北方群体。并发现血清型Ａ２有６种基因亚型,包括Ａ＊０２０１、０２０３、０２０５、０２０６、０２０７、０２１０,其中以０２０１为主体。结论中国南北人群的遗传背景存在一定的差异,Ａ２基因亚型分型在器官移植配型中有重要意义。