Identification of HLA-A*0224: implications for PCR-SSP HLA typing

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.     

Identification of a novel allele HLA-B*7805 in a Japanese female

A new HLA-B*78 allele, B*7805, was identified in a healthy Japanese female. The results of her serological HLA class I typing showed an unusual Bw4/Bw6 pattern with strongly positive reactivity to anti-Bw6, i.e. A24, -, B52, -, Bw4, Bw6. In DNA typing, she was typed as A*24, -, B*52, B*78-like, Cw1202, -, (Bw4, Bw6). Cloning and sequencing of exon 2 and exon 3 of her B locus genes revealed a new allele B*7805. The cloned B*7805 differed from B*78021 by three nucleotide substitutions in exon 2 at position 259 (A to G), 261 (C to G) and 272 (A to C), and contained sequences defining Bw6 motif in the region of codon 77 to 83.     

Identification of the novel allele HLA-A*6813 in two members of a family of Syrian origin: implications for bone marrow transplantation

The identification of the new allele HLA-A*6813, which was found in a woman of Syrian origin and her son, is described. In the sequence analysis the new allele differs from A*68011 by positions 259 (A>G) and 261 (C>G) in exon 2. As the structure is thus identical to the HLA-A consensus sequence it is likely that the new allele originated by gene conversion. At the protein level, the new allele has one amino acid difference from A*6801 (Asn63Glu), which results in a distinct banding pattern in one dimensional-isoelectric focusing. Amino acid residue 63 contributes to the formation of pocket A and B and is thus important for peptide binding. A*6813 was serologically detectable only by two of six polyclonal, but by three monoclonal antisera. The restricted serological A68 activity may be explained by altered peptide binding as presented peptides can affect the serological recognition of major histocompatibility complex (MHC) class I molecules. Moreover, our findings suggest that a possible mismatch with the other known A*68 variants may impair clinical outcome of bone marrow transplantation.     

Characterization of a novel HLA-C allele,Cw*0315

The presence of an unusual HLA class I reactivity pattern was detected in a Caucasoid-Asian individual by PCR-sequence specific primer (PCR-SSP) typing. Exons 2 and 3 were characterized using PCR-sequence-based typing (PCR-SBT) and were found to contain a novel Cw*03 sequence, Cw*0315. In the region studied, Cw*0315 was comprised mainly of the Cw*0302 sequence, but at four positions it contained nucleotides normally only found in other HLA Cw locus alleles. These positions each resulted in an amino acid substitution.     

HLA-B*07 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-B*07 alleles and their haplotypic associations with HLA-A, -C and -DRB1 loci in 489 healthy unrelated Koreans, including 214 parents from 107 families. All of the 45 samples (9.2%) typed as B7 by serology were analyzed for B*07 alleles using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method. Two different B*07 alleles were detected: B*0702 (allele frequency 0.041) and B*0705 (0.005). Two characteristic haplotypes showing strong linkage disequilibrium in Koreans were A*2402-Cw*07-B*0702-DRB1*0101 (haplotype frequency 0.028) and A*2901-B*0705-DRB1*0803 (0.005). The characteristic haplotype A*2901-B*0705-DRB1*0803, found in 100% (5/5) of B*0705-positive individuals, has not been previously described in other ethnic groups. HLA-B7 alleles comprise distinctive extended haplotypes in the Korean population. The probability of HLA-B7 allele mismatches among ABDR-matched unrelated donor-recipient pairs is expected to be low in Koreans.     

PON1Q192R基因多态性与冠心病患者使用氯吡格雷疗效的关系

目的：探讨不同民族PON1Q192R等位基因变异频率以及PON1Q192R基因多态性与冠心病患者氯吡格雷抵抗（CR）的关联性。方法：纳入新疆医科大学第二附属医院2020年1月至2020年12月使用氯吡格雷且诊断为冠心病的患者127例,患者每日服用氯吡格雷75 mg,5 d后用血栓弹力图测定相关参数,并进行CYP2C19*2、CYP2C19*3、CYP2C19*17和PON1Q192R基因分型检测。结果：不同民族之间PON1Q192R基因突变频率差异具有统计学意义（P <0.05）,患者的血栓弹力图参数结果显示,PON1Q192R基突变并不会显著降低氯吡格雷疗效。结论：PON1Q192R基因突变频率与冠心病患者氯吡格雷反应的相关性还需要进一步研究。     

切线时间常数在慢性阻塞性肺疾病及肺心病患者F-V曲线形状转变中的变化及临床意义

目的　探讨切线时间常数 ( τt)在慢性阻塞性肺疾病 ( COPD,慢阻肺 )和肺心病患者 F- V曲线形状转变中的变化及临床意义。方法　测定了 90例缓解期 COPD患者 (慢支 43例 ,肺气肿 47例 )及 31例合并肺心病患者的 F- V曲线。并在 F- V曲线上测量高、中、低肺容积的切线时间常数 τt75 、τt5 0 、τt2 5 ,与正常人和吸烟者的 τt作对比分析。结果　 1正常范围内 F- V曲线形状呈平台型、直线型、凸型和凹型 4种 ,| τt75 | >1s或 <1s,τt2 5 <1s,τt关系呈“青少年式”或“老年式”;2轻、中度异常的 F- V曲线呈凸型 ,| τt75 | <1s,τt2 5 ≈ 1s或 >1s,τt 关系呈“喇叭式”改变 ;3严重异常的 F- V曲线形状呈双曲线型 ,| τt75 | <1s,τt2 5 =4s～ 10 s,τt关系呈“塔式”改变。结论　双曲线型、τt2 5 极度延长和“塔式”改变是判断病情严重性的三大重要标志。该方法简便准确 ,利于在临床推广应用     

Efficacy of a rational algorithm to assess allergy risk in patients receiving the BNT162b2 vaccine

Among 6146 hospital employees, 118 subjects with severe allergic background were identified through a screening questionnaire and stratified into 3 groups (Low-risk (LR), Intermediate (IR) and High-risk (HR) group), based on their allergic anamnesis.Data reports on hypersensitivity reactions (HypR) have been collected in both allergic and non-allergic subjects. Seventeen patients (14%) in the allergic population had a HypR after the first, the second or both doses. Skin manifestations were the most frequent ones. Allergic events were more frequent in HR (35%) than IR (10%; p = 0.005) or LR (0%; p = 0.074) subjects. No patient had anaphylaxis. All patients completed the vaccination schedule.13 HypR occurred in patients without severe allergic background (13/6028, 0,2%) including one (1/6148, 0.016% of total population) WAO grade-4 anaphylaxis.Our data suggest that BNT162b2 mRNA Covid-19 vaccine is relatively safe also in patients with severe allergic background; however, some precautions are required for high-risk patients.     

Acute unsolicited adverse events following BNT162b2 vaccine in Saudi Arabia,a real-world data

BackgroundAcute adverse events and anaphylaxis were reported after the administration of coronavirus disease (COVID-19) mRNA vaccines. We aim to explore the nature and outcome of adverse events following BNT162B2 vaccine in a community vaccination center, Riyadh, Saudi Arabia.MethodWithin 30 min post vaccination, all acute adverse events (AAEs) that occurred before March 31st, 2021, and in people older than 16 years were reviewed (AAE group). We used the case definition of Brighton collaboration on vaccine safety to define anaphylaxis. Patients’ demographics, comorbidities, allergy history, and outcome at disposition were collected. Observation duration after vaccination was short (<15 min) or extended (<3 h). Statistical analysis was performed to study AAEs association with the study variables and outcomes.ResultsOut of 71,221 vaccine recipients, 144 (0.002%) had developed 345 AAEs, at a rate of 48.4 events per 10,000 dose administered. The majority of cases in AAE group were first dose recipients (93.8%) and previously healthy (59%), while the minority had a previous history of allergy (6.3%) or a laboratory-confirmed COVID-19 (4.2%). We found a significant association between female gender and the occurrence of any AAE (p-value = 0.002). Per every 10,000 doses administered, non-anaphylactic AAEs were dizziness (17.8), headache (9.7), nausea (7.1), or syncope (3.2). Only one in every ten AAEs was considered serious and resulted in an extended observation (4.8 per 10,000 doses), but only 1/144 required hospitalization for non-anaphylaxis reasons (0.1 per 10,000 doses). According to the Brighton collaboration definition of anaphylaxis, no single case of high certainty anaphylaxis was recorded. No death was documented in this cohort.ConclusionAcute adverse events due to BNT162b2 vaccine were rare and mostly non-serious with a tendency to occur more in women. Further prospective studies on larger vaccine recipients to evaluate the incidence of anaphylaxis in the Saudi population are warranted.