Expression of activation markers on basophils in a controlled model of anaphylaxis

BACKGROUND: Anaphylaxis has variable clinical presentations and lacks reliable biomarkers. Expression of activation markers on basophils has been useful in assessing sensitization in IgE-mediated diseases but has not been examined in vivo in anaphylaxis. OBJECTIVE: The study's goals were to assess the baseline expression of activation markers on basophils in individuals with a sting reaction history, the degree of change in expression of these markers after intentional sting challenge, and the relationship between in vitro and in vivo activation marker expression. METHODS: Patients allergic to insect venom were enrolled and grouped by clinical category defined by a history of a systemic or large local reaction and use of venom immunotherapy. Blood was collected before and after sting challenge. Enriched basophils were analyzed for activation marker expression. In select subjects, basophils were examined after in vitro stimulation with insect venom for activation marker expression and histamine release. RESULTS: Of 35 sting-challenge participants, 21 provided adequate samples for analysis. Pre-sting basophil CD63 expression was significantly higher in systemic reactors on immunotherapy. Following sting challenge, the rise in basophil CD69 expression and CD203c was significantly higher in systemic reactors on immunotherapy. Levels of activation markers on basophils were greater after in vitro venom stimulation than after in vivo challenge. CONCLUSION: Broader shifts in expression of basophil activation markers after in vivo challenge occurred among subjects with a history of in vivo systemic anaphylaxis despite venom immunotherapy. CLINICAL IMPLICATIONS: Basophil activation markers may be potential biomarkers for anaphylaxis.     

Clinical and laboratory factors contributing to uninterpretable beryllium lymphocyte proliferation tests (BeLPT)

Background

The beryllium lymphocyte proliferation test (BeLPT), has become the principal clinical test for detecting beryllium sensitization and chronic beryllium disease. Uninterpretable BeLPT results can occur in a small but significant proportion of tests from poor lymphocyte growth (PG) or over proliferation of lymphocytes (OP). The clinical and laboratory causes of uninterpretable results are not known.

Methods

BeLPT data from the US Department of Energy‐supported Former Worker Screening Program were analyzed for a 10‐year period. Drivers of uninterpretable BeLPTs were investigated using multivariable models and classification techniques.

Results

Three participant attributes were significantly associated with PG, while OP showed no significant associations. Serum lot for the lymphocyte growth medium accounted for 21% of the variation in PG and 16% in OP.

Conclusion

Serum lots influence the likelihood of having uninterpretable BeLPT. To better understand uninterpretable results and possibly reduce their occurrence, additional laboratory‐related factors should be addressed.

     

Cardiac pathology after valve replacement by disc prosthesis: A study of 61 necropsy patients

Clinical and necropsy observations are described in 61 patients who had one or more cardiac valves replaced with a discoid prosthesis of the Hufnagel type. The most common (31 percent) cause of death among the 45 patients who died early (less than 65 days after operation) appeared to be prosthetic disproportion; that is, the prosthesis was too big for the aorta or ventricular cavity into which it was inserted so that inadequate space was present between the margins of the disc and the endocardium of ventricle or intima of aorta. Prosthetic thrombosis occurred in only 3 of the 45 patients who died early, but poppet movement appeared considerably altered in each. In contrast, thrombi were observed on a prosthesis in 14 of the 16 patients who died late (4 to 47 months [average 21] postoperatively), but in none did the thrombi appear of sufficient size to alter poppet function. Excessive bleeding occurred in 11 (24 percent) of the 45 early deaths and was primarily related to the insertion of a patch in the root of the aorta. Uncorrected valvular disease either by itself or by its ability to alter function of the prosthesis appeared responsible for death in 6 (13 percent) of the 45 patients who died early and in 2 (6 percent) of the 16 who died late. Insertion of a mitral poppet disc in a patient with uncorrected aortic regurgitation, even of mild degree, may be hazardous because the aortic regurgitant jet stream may interfere with proper function of the mitral disc. Likewise, insertion of a poppet disc only in the aortic valve position in a patient with combined aortic and mitral regurgitation may considerably increase the degree of mitral incompetence because the aortic prosthesis is intrinsically obstructive.Disc wear or variance was observed in all but one prosthesis in place for more than 1 year. Although hemolytic anemia of significant degree was not observed in any of the 16 patients who died late, the occurrence of renal hemosiderosis in 13 of the 16 patients indicates that the poppet disc prosthesis is considerably traumatic to erythrocytes. Thus, this type of prosthesis is not an ideal substitute cardiac valve. It clots, despite anticoagulant therapy, it is intrinsically stenotic, portions of it, that is, the disc, degenerate, and it causes hemolysis to erythrocytes.     

Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study

BACKGROUND: Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A(1c) (HbA(1c)) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain. METHODS: We conducted a prospective case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study. Using proportional hazards models, we assessed the relation between HbA(1c) level and incident CHD during 8 to 10 years of follow-up. RESULTS: In adults with diabetes, the relative risk (RR) of CHD was 2.37 (95% confidence interval [CI], 1.50-3.72) for the highest quintile of HbA(1c) level compared with the lowest after adjustment for CHD risk factors. In persons without diabetes, the adjusted RR of CHD in the highest quintile of HbA(1c) level was 1.41 (95% CI, 0.90-2.30); however, there was evidence of a nonlinear relationship in this group. In nondiabetic adults, HbA(1c) level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA(1c) levels. In the adjusted model, the RR of CHD for a 1-percentage point increase in HbA(1c) level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA(1c) level greater than 4.6%. In diabetic adults, the RR was 1.14 (95% CI, 1.07-1.21) per 1-percentage point increase in HbA(1c) across the full range of HbA(1c) values. CONCLUSION: Elevated HbA(1c) level is an independent risk factor for CHD in persons with and without diabetes.     

High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis

We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.     

Origin of leukemic relapse after bone marrow transplantation: comparison of cytogenetic and molecular analyses

Leukemic relapse following bone marrow transplant (BMT) is generally due to the recurrence in recipient cells, but may rarely occur as a result of donor cell transformation. Donor cell relapse is generally identified using cytogenetic markers such as the sex chromosomes. Recently, molecular techniques have been used to identify the origin of bone marrow cells by their DNA restriction fragment length polymorphisms. We describe the case of a male pediatric patient who had a leukemic relapse 30 months following BMT from his sister. Both cytogenetic and molecular techniques were used to identify the origin of the leukemic relapse. Cytogenetic analyses indicated the absence of the Y chromosome and the presence of a donor cell type 9qh polymorphism, suggesting a donor cell relapse. Molecular analyses also indicated the absence of the Y chromosome but demonstrated the recurrence of recipient DNA markers from three other chromosomes, suggesting a recipient cell relapse. While the leukemic cell lineage cannot be definitively assigned in this case, our results suggest that caution must be exercised when assigning leukemic cell lineage following post-BMT relapse.