Heavy chain disease.
ABSTRACT The heavy chain diseases (HCDs) are rare B-cell malignancies that are distinguished by the production of a monoclonal immunoglobulin heavy chain (HC) without an associated light chain by the malignant B-cells. There are three types of HCD defined by the class of immunoglobulin (Ig) HC produced: IgA (alpha-HCD), IgG (gamma-HCD), and IgM (mu-HCD). Alpha-HCD is the most common and occurs most commonly as intestinal malabsorption in a young adult from a country bordering the Mediterranean Sea. Treatment consists of antibiotics and improved nutrition and hygiene. Surgery is occasionally required for patients with bulky masses at risk for bowel perforation. If there is no response to antibiotics or if aggressive non-Hodgkin's lymphoma (NHL) is diagnosed, the patient should be treated with chemotherapy. Gamma- and mu-HCD are rare and essentially are found in patients with a B-cell NHL that produces an abnormal Ig heavy chain. These patients occasionally may be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS with NHL should be administered chemotherapy. Screening the serum and urine of patients with lymphoplasmacytoid NHL would likely identify more patients with gamma- or mu-HCD.
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ABSTRACT: Introduction of spectrophotometric detection of serum indices and decision rules to be carried out manually increased the detection rate of relevant hemolysis 6.04- fold. After introduction of the algorithm in the LIS, the detection rate for relevant serum interference was 69.37- fold higher than in the first 1-year period. For icteric samples, a large increase in reported interference was observed: whereas the occurrence of icterus in the sample was not reported at all in the first period, during the second 1-year period, 0.05% of specimens were reported as significantly icteric, causing deviations in the assay results. This number was increased 10-fold (0.54%) in the third period. Interestingly, only one case of lipemia was reported in the first period and none in the second period. Appar- ently, automated spectrophotometric detection together with written instructions in the second 1-year period did not lead to adequate reporting to the clinician. In the third year, 1012-fold more cases of clinically relevant lipemia were reported than in the first year. It should be pointed out here that the evaluation performed and the observed quality improvement depend on the validity of the auto- mated procedure. Summarizing, we believe that this algorithm can be used as a blueprint for processing of test results in general. Every test result is now evaluated automatically in real time against predetermined tolerance limits for the extent of interfering substances, and the algorithm is designed as an almost technician-independent method. We encourage cooperation in this project, and copies of the MISPL algorithm and tolerance tables can be obtained free of charge from the corresponding author.
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ABSTRACT: Survival of mature B cells is thought to depend on the BCR signaling (BCR) because ablation of either H chain (HC) expression or BCR signaling causes B cells to rapidly disappear. Whether a complete BCR is required for survival of mature B cells is not known. To address this question, we generated a mouse in which we can repress the expression of a transgenic Ig L chain (IgL) by doxycycline (IgL-repressible mouse). Repression of IgL abrogated expression. Surprisingly, however, IgL-negative B cells survived longer than 14 wk, expressed signal-competent HC on the cell's surface, and active unfolded protein response factors. Like postgerminal center B cells, IgL-negative B cells were small lymphocytes, not dividing and expressed Bcl-6. Our results indicate that expression of unpaired HC, as it may occur as a consequence of Ag ligation, somatic hypermutation, or receptor editing, facilitates the survival of cells either by inducing receptor signaling or by inducing unfolded protein response and/or the expression of survival genes such as Bcl-6.The Journal of Immunology 09/2007; 179(3):1659-68. · 5.52 Impact Factor
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ABSTRACT: A substantial fraction of eukaryotic gene products are synthesized by ribosomes attached at the cytosolic face of the endoplasmic reticulum (ER) membrane. These polypeptides enter cotranslationally in the ER lumen, which contains resident molecular chaperones and folding factors that assist their maturation. Native proteins are released from the ER lumen and are transported through the secretory pathway to their final intra- or extracellular destination. Folding-defective polypeptides are exported across the ER membrane into the cytosol and destroyed. Cellular and organismal homeostasis relies on a balanced activity of the ER folding, quality control, and degradation machineries as shown by the dozens of human diseases related to defective maturation or disposal of individual polypeptides generated in the ER.Physiological Reviews 11/2007; 87(4):1377-408. · 30.17 Impact Factor