X-irradiation and gamma-irradiation inactivate lymphocytes in blood components.

BACKGROUND: Irradiation of selected blood components is standard practice for the prevention of transfusion-associated graft-versus-host disease (TA-GvHD). Currently, gamma-irradiation is the most widely used form of irradiation, but there is an increasing interest in X-irradiation, which is considered to be functionally equivalent and safer. However, there is a paucity of contemporary data regarding the ability of X-irradiation to inactivate lymphocytes in blood components. Therefore, the effect of gamma- and X-irradiation on lymphocyte viability and function in blood components was compared. STUDY DESIGN AND METHODS: Lymphocytes were isolated from venous blood by density gradient centrifugation, spiked into plasma/SSP+ to simulate a blood component, and either gamma- or X-irradiated. The phenotype of the isolated lymphocytes was confirmed. Lymphocyte viability was measured using a LIVE/DEAD assay, and function was assessed using mixed lymphocyte culture and CD69 expression post-phorbol-12 myristate 13-acetate (PMA) stimulation. RESULTS: Lymphocyte viability and CD69 expression following PMA stimulation were significantly reduced by both gamma-irradiation and X-irradiation in simulated blood components. Allorecognition and allostimulation were also significantly reduced by both gamma-irradiation and X-irradiation. CONCLUSION: Lymphocyte viability and function are reduced to a similar extent by gamma- and X-irradiation in simulated blood components. As such, X-irradiation is suitable for the irradiation of blood components and, in terms of lymphocyte inactivation, could be used instead of gamma-irradiation.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways.

BACKGROUND: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. METHODS: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. RESULTS: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. CONCLUSIONS: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.