B Cells and Humoral Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
In these diseases, called dysgammaglobulinemias, absence or low levels of one or more Ig classes or subclasses results in variable immunodeficiency. The most common dysgammaglobulinemia is IgA deficiency. The estimated frequency is approximately 1:6–700 healthy blood donors. Thus, IgA deficiency (1–3% of the normal serum level) is most often asymptomatic. Usually both IgA isotypes (IgAl and IgA2) are absent, but selective deficiency of one IgA isotype has been observed. The serum level of other isotypes is most often normal, but a significant fraction of individuals will have associated deficiencies of IgG2 and IgG4 and/or IgE (associated IgG 1 or IgG3 deficiency is rare). (An) unidentified gene(s) located in the class III region of the major histocompatibility locus are important in some cases, although probably in conjunction with environmental factors (such as viral infections) and genes at other loci. Like common variable immunodeficiency, IgA deficiency may arise from any lesion affecting the selective induction of IgA production by B cells. There is only a single report of IgA deficiency as a result of a deletion involving Cα1. One case has been reported in which the patient was unable to synthesize secretory component and could not produce secretory IgA. This individual presented with chronic intestinal candidiasis.
Human T-Lymphotropic Virus
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
Japan is a key endemic area of HTLV-I infection. There are some endemic areas in the south of Japan, such as Kyusyu Island, Shikoku Island, and Okinawa Island (Yoshida et al. 1982). Although the prevalence in the general population varies from 0% to 37% (Yoshida et al. 1982), the migration of infected Japanese individuals has recently changed the prevalence throughout the whole of Japan. In the Caribbean islands, the rate of HTLV-I infection is observed to be high, and the prevalence is estimated with approximately 5% in Jamaica (Murphy et al. 1991). Africa is estimated to be the origin of HTLV-I because all different primate T-lymphotropic viruses (PTLV) have been found there. Phylogenetic studies also suggest central Africa as the birthplace of PTLV. In Africa, although the study of the region is limited, the prevalence varies from 0.5% to around 5% (Dumas et al. 1991). In Brazil, the highest prevalence (1.35%) was reported for the central area and the coast, with the lowest (0.08%) in the north and south (Goncalves et al. 2010). In addition, there are smaller endemic foci in Australia (Aboriginal populations), Iran, and Papua New Guinea (Goncalves et al. 2010; Yoshida et al. 1982). In nonendemic areas such as Europe and North America, HTLV-I infection is mainly observed in immigrants from endemic areas, their offspring, and sexual contacts, as well as intravenous drug users and sex workers. From the data of blood donors in Europe and North America, the prevalence is quite low, for example, 0.0039% in France and 0.01%-0.03% in the United States and Canada (Biggar et al. 2006; Murphy et al. 1991).
Pharmacologic alternatives to blood
Jennifer Duguid, Lawrence Tim Goodnough, Michael J. Desmond in Transfusion Medicine in Practice, 2020
Patients donating autologous blood under standard conditions (i.e. one blood unit weekly8,9) have an inadequate response of endogenous erythropoietin to blood-loss anemia, suggesting a role for EPO therapy in facilitating autologous blood donation. This was confirmed10,11 in a study comparing aggressive autologous blood donation (up to 6 units over a 3-week preoperative interval) with EPO therapy in patients undergoing orthopedic surgery. However, a subsequent clinical trial12 in orthopedic patients demonstrated that for autologous blood donors who were not anemic (hematocrit > 39%) at first donation, no clinical benefit (defined as reduced allogeneic blood exposure) was seen with EPO therapy when compared with aggressive autologous phlebotomy alone. Thus, for non-anemic patients, autologous blood donation remains an option if they can tolerate aggressive blood phlebotomy (i.e. up to 6 units over 3 weeks) and thereby achieve stimulation of erythropoiesis via their endogenous EPO response.13
Establishing reference intervals for islet autoantibodies in Han Chinese type 1 diabetes
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
Yu Fu, Chen Zhang, Yong Gu, Shibin Ge, Jianhua Li, Jianlin Feng, Li Zhang, Wei Liu, Heng Chen
The exclusion criteria for screening the apparently healthy subjects were as follows: (a) incomplete basic information or erroneous data resulting from negligence in data entry; (b) individuals testing positive for any of the following: GADA, IA-2A, ZnT8A, and IAA using RBA method (the “gold standard” for measuring IAbs [22]); (c) individuals with BMI < 18.0 kg/m2 or > 25.0 kg/m2; (d) individuals with a history of disease conditions, including thyroid disease, malignant neoplasm, and liver cancer, which influence insulin secretion; (e) individuals with a history of autoimmune diseases, including rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus; (f) serum samples exhibiting hemolysis and lipemia on visual examination; (g) alcohol consumption within 24 h prior to blood collection; (h) blood donation within 3 months of sample collection; (i) outliers. Outliers were removed based on the one-third ratio of the D/R rule [23], where D is the absolute difference between the highest (or lowest) observed value and the value it is numerically closest to; R is the range of all observed values. If the observed value of D was equal to or greater than one-third of R, then that value was rejected. Based on the responses in the questionnaire and laboratory measurements, 138 apparently healthy subjects of Chinese Han population were included in analysis, and 39 individuals were excluded, including 15 subjects with positive IAbs, 16 subjects with BMI < 18.0 kg/m2 or > 25.0 kg/m2, and 8 outliers.
Pharmacokinetics, safety, and tolerability of TQC3564, a novel CRTh2 receptor antagonist: report of the first-in-human single- and multiple-dose escalation trials in healthy Chinese subjects
Published in Expert Opinion on Investigational Drugs, 2022
Xiaojiao Li, Qianqian Li, Tianliang Ji, Hong Zhang, Jingrui Liu, Min Wu, Hong Chen, Jinfeng Lou, Chengjiao Liu, Zhongnan Xu, Yanhua Ding
All subjects recruited in this study were healthy Chinese volunteers. The inclusion criteria of this study were as follows: (a) male or female (nonpregnant) adults aged 18–55 years old; (b) body mass index of 18–28 kg/m2 and body weight ≥ 50 kg (men) or 45 kg (women); and (c) no clinically significant abnormal results in clinical laboratory tests during screening, physical examination, or medical history. Meanwhile, the exclusion criteria were as follows: (a) smoked more than 5 cigarettes a day within 3 months before the trial or abuse of alcohol and/or drugs; (b) administration of any medication within 14 days prior to the initial dose of the investigational drug or during the clinical trial; (c) blood donation within 3 months; (d) treated with inducers or inhibitors of CYP3A4, P-gp, or Bcrp within 3 months; and (e) enrolled in a clinical trial that was an investigation of a new drug within 3 months.
Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor
Published in Platelets, 2018
Ivan Budnik, Boris Shenkman, Hagit Hauschner, Isaac Zilinsky, Naphtali Savion
The study was approved by the local ethics committee, and each volunteer signed a written informed consent in accordance with the Declaration of Helsinki. Blood was drawn from adult healthy male and female volunteers (ranging in age from 21 to 54 years) who were free of any medication affecting the hemostasis system for at least 2 weeks prior to blood donation. The first 2 mL of blood was discarded. Blood samples were collected into tubes containing 3.2% sodium citrate or EDTA (Vacuette; Greiner Bio-One GmbH, Kremsmunster, Austria). Whole blood (WB) samples were rested for 30 min at room temperature and processed within 3 h after collection. The samples were considered suitable for the study when the platelet count was within the range of 2–4 × 108 mL−1 and hematocrit of 36–48%, which were determined in EDTA-anticoagulated blood and measured in LH-750 device (Beckman Coulter, Oakley, UK). Fibrinogen concentration in plasma of citrated blood was determined by the Clauss method ranging at 2.5–3.6 g/L. Prothrombin time and activated partial thromboplastin time were within normal ranges and measured in ACL TOP 700 (Instrumentation Laboratory, Bedford, MA, USA).
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