Kurtis R. Bray

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD.

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8(+) T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.

CA-549 is a circulating breast cancer-associated antigen that reacts with monoclonal antibody BC4E 549. Biochemical characterization of CA-549 revealed that it is an acidic (isoelectric point 5.2) glycoprotein that exhibits two bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of apparent molecular weights of 400,000 and 512,000. Immunohistochemical staining of unfixed frozen tissue sections of human breast tumors and a variety of benign tissues with BC4E 549 revealed no preferential staining of tumor over benign breast tissue and cross-reactivity with a wide range of other benign tissues including kidney, liver, lung, colon, pancreas, ovary, and spleen. Serum levels of CA-549 were initially tested by an enzyme-linked immunosorbent assay inhibition using BC4E 549. This assay showed that CA-549 concentrations were elevated in 19 of 27 sera from patients with advanced breast cancer compared to 0 of 22 and 0 of 129 sera from benign breast disease patients and healthy females, respectively. These preliminary data suggested that CA-549 was a useful breast tumor marker; thus BC4E 549 was adapted to a sandwich immunoradiometric assay format suitable for routine use in the clinical laboratory and its performance was evaluated on a panel of 668 serum samples. The test detected significant concentrations of CA-549 in the sera of 40 of 80 patients with advanced breast cancer, 1 of 30 with early breast cancer, 4 of 19 with advanced lung cancer, 2 of 40 with advanced colon cancer, and 5 of 29 with advanced prostate cancer. The test showed a high degree of specificity, producing false-positives in only 3 of 79 benign breast patients, 2 of 25 benign liver patients, 2 of 70 benign colon patients, 2 of 19 benign lung patients, 0 of 20 benign prostate patients, and 3 of 257 healthy individuals. These data represent an overall 50% sensitivity and 98% specificity as a test for advanced breast cancer. These data indicate that this immunoradiometric assay is a useful test for the detection of circulating CA-549 in advanced breast cancer patients and suggest that it may prove useful as a monitor in the management of that disease.