Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity

BACKGROUND AND OBJECTIVES: In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. MATERIALS AND METHODS: The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. RESULTS: Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. CONCLUSIONS: Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.     

Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication: A Meta-Analysis

ObjectivesThe purpose of this study was to systematically explore the added value of biomarkers of vascular inflammation for cardiovascular prognostication on top of clinical risk factors.BackgroundMeasurement of biomarkers of vascular inflammation is advocated for the risk stratification for coronary heart disease (CHD).MethodsWe systematically explored published reports in MEDLINE for cohort studies on the prognostic value of common biomarkers of vascular inflammation in stable patients without known CHD. These included common circulating inflammatory biomarkers (ie, C-reactive protein, interleukin-6 and tumor necrosis factor-a, arterial positron emission tomography/computed tomography and coronary computed tomography angiography–derived biomarkers of vascular inflammation, including anatomical high-risk plaque features and perivascular fat imaging. The main endpoint was the difference in c-index (Δ[c-index]) with the use of inflammatory biomarkers for major adverse cardiovascular events (MACEs) and mortality. We calculated I² to test heterogeneity. This study is registered with PROSPERO (CRD42020181158).ResultsA total of 104,826 relevant studies were screened and a final of 39 independent studies (175,778 individuals) were included in the quantitative synthesis. Biomarkers of vascular inflammation provided added prognostic value for the composite endpoint and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95% CI: 1.7-4.1 and 3.1, 95% CI: 1.8-4.5, respectively). Coronary computed tomography angiography–related biomarkers were associated with the highest added prognostic value for MACEs: high-risk plaques 5.8%, 95% CI: 0.6 to 11.0, and perivascular adipose tissue (on top of coronary atherosclerosis extent and high-risk plaques): 8.2%, 95% CI: 4.0 to 12.5). In meta-regression analysis, the prognostic value of inflammatory biomarkers was independent of other confounders including study size, length of follow-up, population event incidence, the performance of the baseline model, and the level of statistical adjustment. Limitations in the published literature include the lack of reporting of other metrics of improvement of risk stratification, the net clinical benefit, or the cost-effectiveness of such biomarkers in clinical practice.ConclusionsThe use of biomarkers of vascular inflammation enhances risk discrimination for cardiovascular events.     

Granulomatous disease in selective IgA deficiency

Although common variable immunodeficiency (CVID) is sometimes associated with sarcoidosis/granulomatous disease, there have only been isolated reports of selective immunoglobulin A (IgA) deficiency and granulomatous disease. We present a patient with IgA deficiency who developed Heerfordt syndrome, a variant of neurosarcoidosis. This specific entity has not been previously reported to occur in IgA deficiency. Our case expands the reported associations of IgA deficiency and provides another example to the paucity of reported cases of sarcoidosis occurring in patients with IgA deficiency. As CVID and IgA deficiency have common underlying genetic factors, such an association is biologically plausible.     

Circulating phenotypic B‐1 cells are decreased in common variable immunodeficiency and correlate with immunoglobulin M levels

B‐1 cells are innate‐like lymphocytes characterized by spontaneous production of ‘natural’ polyspecific antibodies, often of self‐specificity, and thought to be responsible for tissue homeostasis, mucosal protection, maintaining resting serum immunoglobulin (Ig)M levels and for early immunoglobulin production following infection. Although defined most clearly in mice, a human B‐1 cell counterpart, defined by the phenotype CD19 or 20⁺CD27⁺CD43⁺CD69 or 70^–, has been proposed recently, facilitating a study of their role in human humoral immunodeficiencies, such as common variable immunodeficiency (CVID). This study examined circulating B‐1 cells in 27 CVID patients in comparison to age‐matched controls (n = 28). Phenotypic putative B‐1 cell proportions varied widely, but there was an overall 60–70% decrease in CVID (0·039 ± 0·033% of lymphocytes, mean ± standard deviation) compared with controls (0·110 ± 0·159% of lymphocytes, P = 0·0012). This decrease was, however, explained largely by concomitant loss of total CD27⁺ memory B cells characteristic of CVID, although those with higher memory B cell proportions appeared to show a true decrease. No age‐related effects were apparent in B‐1 cell proportions. However, among CVID patients, there was a strong positive correlation between the B‐1 cell proportion and serum IgM levels, a relationship that was not evident for IgA, nor was there a relationship between memory B cell proportions and serum IgM. Patients with CVID have fewer circulating putative phenotypic B‐1 cells, which largely reflected the overall decrease in memory B cells. However, B‐1 cell proportions correlated with resting serum IgM levels, suggesting a possible role in IgM deficiency in CVID.     

生物光声层析成像中超声探测器特性对图像质量的影响及解决方法

生物光声层析成像(PAT)是一种多物理场耦合的新型复合功能成像方法,对肿瘤和心血管疾病等的早期检测和准确诊断具有极高的研究价值。在PAT图像重建中,为了简化问题,通常假设超声探测器是具有全向响应的理想点探测器,在目标周围形成一个连续完整的测量面,且不考虑探测器的空间脉冲响应(SIR)和电脉冲响应(EIR)对成像质量的影响。但在实际应用中,这一理想假设会导致成像分辨率和图像质量的下降。从有限孔径效应、SIR和EIR、方向性、扫描半径、有限测量角度和有限带宽以及位置不确定性等6个方面,就超声探测器特性对图像重建的影响,综述相应的解决方法,对比不同方法的优缺点以及适用范围,并展望未来可能的发展方向。     

Genetic relatedness of Mycobacterium avium-intracellulare complex isolates from patients with pulmonary MAC disease and their residential soils

Mycobacterium avium-intracellulare complex (MAC) strains were recovered from 48.9% of residential soil samples (agricultural farms (n = 7), residential yards (n = 79), and planting pots (n = 49)) of 100 pulmonary MAC patients and 35 non-infected control patients. The frequency of MAC recovery did not differ among soil types or among patients regardless of the presence of pulmonary MAC disease, infecting MAC species or period of soil exposure. Variable numbers of tandem repeats (VNTR) analysis for MAC clinical and soil isolates revealed 78 different patterns in 47 M. avium clinical isolates and 41 soil isolates, and 53 different patterns in 18 M. intracellulare clinical isolates and 37 soil isolates. Six clinical and corresponding soil isolate pairs with an identical VNTR genotype were from case patients with high soil exposure (≥2 h per week, 37.5% (6/16) with high exposure compared with 0.0% (0/19) with low or no exposure, p <0.01), suggesting that residential soils are a likely source of pulmonary MAC infection.     

河南省医用加速器多叶光栅小野输出因子验证测量方法研究

目的 调查放射治疗计划系统(TPS)计算的多叶光栅(MLC)小野输出因子,研究用0.015 cc电离室验证小野输出因子的测量方法。方法 在河南省选择8台可开展调强放射治疗的医用加速器,调查TPS计算的小野输出因子并与国际原子能机构(IAEA)推荐的出版值进行比。如果2 cm×2 cm照射野相对偏差超出IAEA要求的±3%,3 cm×3 cm、4 cm×4 cm、6 cm×6 cm照射野相对偏差超出IAEA要求的±2%,则用0.015 cc电离室和Unidos剂量仪进行测量验证。结果8台医用加速器的TPS计算小野输出因子与出版值比较,5台相对偏差符合IAEA要求,占调查总台数的62.5%,3台相对偏差超过IAEA要求,占调查总台数的37.5%。用针尖电离室测量验证,3台测量结果均符合IAEA要求。结论 河南省部分医用加速器TPS计算的MLC小野输出因子,需要现场实施小电离室测量修正,测量值作为制定放射治疗计划的依据。     

A ph mesh refinement method for optimal control

A mesh refinement method is described for solving a continuous‐time optimal control problem using collocation at Legendre–Gauss–Radau points. The method allows for changes in both the number of mesh intervals and the degree of the approximating polynomial within a mesh interval. First, a relative error estimate is derived based on the difference between the Lagrange polynomial approximation of the state and a Legendre–Gauss–Radau quadrature integration of the dynamics within a mesh interval. The derived relative error estimate is then used to decide if the degree of the approximating polynomial within a mesh should be increased or if the mesh interval should be divided into subintervals. The degree of the approximating polynomial within a mesh interval is increased if the polynomial degree estimated by the method remains below a maximum allowable degree. Otherwise, the mesh interval is divided into subintervals. The process of refining the mesh is repeated until a specified relative error tolerance is met. Three examples highlight various features of the method and show that the approach is more computationally efficient and produces significantly smaller mesh sizes for a given accuracy tolerance when compared with fixed‐order methods. Copyright © 2014 John Wiley & Sons, Ltd.