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Bloch E.M.,Blood Systems Research Institute BSRI | Reed W.F.,Blood Systems Research Institute BSRI | Reed W.F.,Cerus Corporation | Lee T.-H.,Blood Systems Research Institute BSRI | And 4 more authors.
Chimerism | Year: 2011

Background: Fetal microchimerism (F-MC), the persistence of fetal cells in the mother, is frequently encountered following pregnancy. The high prevalence of F-MC in autoimmune disease prompts consideration of the role for immune tolerance and regulation. This study examines the association between F-MC and multiple sclerosis (MS), an autoimmune disorder, of undetermined etiology. Results: 21 out of 51 MS-positive subjects (41%) were classified as positive for F-MC; 4 of 22 (18%) of MS-negative sibling controls, were also positive for MC (p = 0.066). Unanticipated F-MC in controls lead to re-evaluation using 30 female singleton cord blood units (CBUs) as a biological control. Four CBUs were low-level positive. Study Design and Methods: Seventy-three female subjects were assigned to three groups according to disease status and pregnancy history: (1) MS positive (+) women with a history of one male pregnancy before symptom onset (n = 27); (2) MS negative (-) female siblings of MS+ women with a history of one male pregnancy (n = 22); and (3) MS+ women that reported never having been pregnant (n = 24). Ten micrograms of genomic DNA obtained from peripheral blood leukocytes of each subject were analyzed for F-MC using allele-specific real-time PCR targeting the SR-Y sequence on the Y-chromosome. MC classification was dichotomous (positive vs. negative) based on PCR results. Conclusion: The association between F-MC and MS warrants further study to define this relationship. F-MC in women self-reporting as nulligravid, supports previous findings that a significant proportion of pregnancies go undetected. This lead to re-validation of a Y-chromosome based assay for F-MC detection. © 2011 Landes Bioscience. Source

Oliveira C.L.,Federal University of Sao Joao del Rei | Liu E.J.,Westat Inc. | Sabino E.C.,Federal University of Sao Paulo | Leao S.C.,Fundacao de Hematologia e Hemoterapia de Pernambuco HEMOPE | And 7 more authors.
Revista Brasileira de Hematologia e Hemoterapia | Year: 2013

Background: Seasonal distribution of blood donation hinders efforts to provide a safe and adequate blood supply leading to chronic and persistent shortages. This study examined whether holidays, geographical area and donation type (community versus replacement) has any impact on the fluctuation of donations. Methods: The numbers of blood donations from 2007 through 2010 in three Brazilian Retrovirus Epidemiological Donor Study II (REDS-II) participating centers were analyzed according to the week of donation. The weeks were classified as holiday or non-holiday. To compare donations performed during holiday versus non-holiday weeks, tabulations and descriptive statistics for weekly donations by blood center were examined and time series analysis was conducted. Results: The average weekly number of donations varied according to the blood center and type of week. The average number of donations decreased significantly during Carnival and Christmas and increased during the Brazilian National Donor Week. The fluctuation was more pronounced in Recife and Belo Horizonte when compared to São Paulo and higher among community donors. Conclusion: National bank holidays affect the blood supply by reducing available blood donations. Blood banks should take into account these oscillations in order to plan local campaigns, aiming at maintaining the blood supply at acceptable levels. Source

Yukl S.A.,University of California at San Francisco | Boritz E.,U.S. National Institutes of Health | Busch M.,Blood Systems Research Institute BSRI | Bentsen C.,Bio Rad Laboratories Inc. | And 25 more authors.
PLoS Pathogens | Year: 2013

There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure. Source

Bloch E.M.,Blood Systems Research Institute BSRI | Bloch E.M.,University of California at San Francisco | Shah A.,Blood Systems Research Institute BSRI | Kaidarova Z.,Blood Systems Research Institute BSRI | And 51 more authors.
Vox Sanguinis | Year: 2014

Background and Objectives: Serologic screening for the major transfusion transmissible viruses (TTV) is critical to blood safety and has been widely implemented. However, actual performance as measured by proficiency testing has not been well studied in sub-Saharan Africa. Therefore, we conducted an external quality assessment of laboratories engaged in transfusion screening in the region. Materials and Methods: Blinded test panels, each comprising 25 serum samples that were pedigreed for HIV, HBsAg, HCV and negative status, were sent to participating laboratories. The panels were tested using the laboratories' routine donor screening methods and conditions. Sensitivity and specificity were calculated, and multivariable analysis was used to compare performance against mode of testing, country and infrastructure. Results: A total of 12 African countries and 44 laboratories participated in the study. The mean (range) sensitivities for HIV, HBsAg and HCV were 91·9% (14·3-100), 86·7% (42·9-100) and 90·1% (50-100), respectively. Mean specificities for HIV, HBsAg and HCV were 97·7%, 97% and 99·5%, respectively. After adjusting for country and infrastructure, rapid tests had significantly lower sensitivity than enzyme immunoassays for both HBsAg (P < 0·0001) and HCV (P < 0·05). Sensitivity also varied by country and selected infrastructure variables. Conclusion: While specificity was high, sensitivity was more variable and deficient in a substantial number of testing laboratories. These findings underscore the importance of proficiency testing and quality control, particularly in Africa where TTV prevalence is high. © 2014 International Society of Blood Transfusion. Source

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