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Immunoglobulin Light Chains (immunoglobulin + light_chain)
Selected AbstractsFibril protein fragmentation pattern in systemic AL-amyloidosisTHE JOURNAL OF PATHOLOGY, Issue 4 2009Stina Enqvist Abstract Immunoglobulin light chain (AL)-amyloidosis was one of the first types of amyloidosis discovered and still little is known about its pathogenic mechanisms. One major obstacle is the very heterogeneous condition; in fact, every patient could be considered to have their own disease since symptoms and outcome vary enormously. The reason for this is not known but intrinsic factors of the immunoglobulin light chain (LC) and the fact that every LC is unique seem to be important. Post-translational modifications such as glycosylation and proteolysis are most certainly involved. By using western blotting, we studied in detail the proteolytic pattern in six patients with AL-amyloidosis of kappa type with the aid of three peptide antisera against two domains in the constant segment and one conserved domain in framework 3 of the variable region. Materials from one to five organs were analysed. The result clearly demonstrates that the fragmentation pattern was similar in amyloid of different organs in one patient but differed greatly between patients. Full-length, N-, and C-terminal fragments were detected with the three antisera. The results strongly support the hypothesis that proteolytic cleavage occurs after fibril formation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Comparative transcriptome analysis to unveil genes affecting recombinant protein productivity in mammalian cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Joon Chong Yee Abstract Low temperature culture (33°C) has been shown to enhance the specific productivity of recombinant antibodies in Chinese hamster ovary (CHO) cells but did not affect antibody productivity in hybridoma (MAK) cells. We probed the transcriptional response of both cells undergoing temperature shift using cDNA microarrays. Among the orthologous gene probes, common trends in the expression changes between CHO and MAK are not prominent. Instead, many transcriptional changes were specific to only one cell line. Notably, oxidative phosphorylation and ribosomal genes were downregulated in MAK but not in CHO. Conversely, several protein trafficking genes and cytoskeleton elements were upregulated in CHO but remained unchanged in MAK. Interestingly, at 33°C, immunoglobulin heavy and light chain showed no significant changes in CHO, but the immunoglobulin light chain was downregulated in MAK. Overall, a clear distinction in the transcriptional response to low temperature was seen in the two cell lines. To further elucidate the set of genes responsible for increased antibody productivity, the expression data of low temperature cultures was compared to that of butyrate treatment which increased specific antibody productivity in both cell lines. Genes which are commonly differentially expressed under conditions that increased productivity are likely to reflect functional classes that are important in the productivity changes. This comparative transcriptome analysis suggests that vesicle trafficking, endocytosis and cytoskeletal elements are involved in increased specific antibody productivity. Biotechnol. Bioeng. 2009;102: 246,263. © 2008 Wiley Periodicals, Inc. [source] Serum free light chain analysis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Matthew S. Davids In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as , and , "free" LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Laryngeal presentation of systemic apolipoprotein A-I,derived amyloidosis,THE LARYNGOSCOPE, Issue 3 2009Aldert J. C. Hazenberg MD Abstract Objective: To study the clinical and pathological characteristics of two patients with laryngeal apolipoprotein A-I (apoA-I)-derived (AApoAI) amyloidosis with the apolipoprotein A-I variants Leu174Ser and Leu178Pro, respectively. The latter variant has not been associated with amyloid before. Study Design: Descriptive report of two patients who presented with laryngeal amyloid presumed to be of localized AL type, but in who further assessments demonstrated systemic amyloidosis. Methods: The larynx was examined by videolaryngostroboscopy. The voice was analyzed with the GRBAS system, phonation times, and phonetography. Laryngeal biopsies were stained with Congo red and analyzed immunohistochemically. Organ function was assessed and tissue involvement by amyloid further determined by rectal biopsy, abdominal fat tissue aspirate, and serum amyloid P component scintigraphy. Results: The appearance of the laryngeal amyloid was unusual in both patients, occurring as small, irregular floppy proliferations affecting the borders of both vocal folds. Amyloid was stained with antibodies to apoA-I and not with antibodies to immunoglobulin light chains. The 45-year-old woman with the previously described amyloidogenic apoA-I Leu174Ser variant had possible involvement by amyloid in joints, peripheral nerves, and heart. Whereas in the 67-year-old man with apoA-I Leu178Pro there was a clinical suggestion of autonomic and cardiac amyloid and histological corroboration of systemic amyloidosis in abdominal fat. Conclusions: Laryngeal symptoms may be the presenting feature of hereditary systemic AApoAI amyloidosis, and comprehensive investigations including apoA-I genotyping are warranted in patients who present with apparently localized laryngeal amyloidosis. The distinctive appearance of the amyloidotic vocal folds described here may further signal the possibility of hereditary AApoAI type. Laryngoscope, 119:608,615, 2009 [source] Hyperosmotic Stress in Murine Hybridoma Cells: Effects on Antibody Transcription, Translation, Posttranslational Processing, and the Cell CycleBIOTECHNOLOGY PROGRESS, Issue 2 2004Zhe Sun Mechanisms for increased antibody production in batch cultures of murine hybridoma cells in response to hyperosmotic stress were investigated. The rates of immunoglobulin transcription and protein translation and posttranslational processing were determined in control and hyperosmotic cultures. Changes in immunoglobulin transcription played a minor role in the increase in antibody production in response to hyperosmotic stress. In contrast, protein translation increased substantially in response to osmotic stress. However, the antibody translation rate remained relatively constant after correcting for the overall increase in protein translation. Cell size and intracellular antibody pool also increased in response to hyperosmolarity. The intracellular antibody pool increased proportionately with the increase in cell size, indicating that hyperosmotic cultures do not selectively increase their intracellular antibody population. Changes in cell cycle distribution in response to osmotic stress and the relationship between the cell cycle and antibody production were also evaluated. Hyperosmotic stress altered the cell cycle distribution, increasing the fraction of the cells in S-phase. However, this change was uncorrelated with the increase in antibody production rate. Immunoglobulin degradation was relatively low (,15%) and remained largely unchanged in response to hyperosmotic stress. There was no apparent increase in immunoglobulin stability as a result of osmotic stress. Antibody secretion rates increased approximately 50% in response to osmotic stress, with a commensurate increase in the antibody assembly rate. The rate of transit through the entire posttranslational processing apparatus increased, particularly for immunoglobulin light chains. The levels of endoplasmic reticulum chaperones did not increase as a fraction of the total cellular protein but were increased on a per cell basis as the result of an increase in total cellular protein. A difference in the interactions between the immunoglobulin heavy chains and BiP/GRP78 was observed in response to hyperosmotic conditions. This change in interaction may be correlated with the decrease in transit time through the posttranslational pathways. The increase in the posttranslational processing rate appears to be commensurate with the increase in antibody production in response to hyperosmotic stress. [source] High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluidACTA NEUROLOGICA SCANDINAVICA, Issue 1 2009B. Arneth Background,,, So far, an inflammation of the central nervous system (CNS) is diagnosed by immunoglobulin measurement in cerebrospinal fluid (CSF) and serum as well as by determination of the oligoclonal bands. With the free kappa and lambda light chains, new markers to diagnose intrathecal synthesis are available. Methods,,, In addition to routine diagnostic tests and the assessment of standard parameters, free immunoglobulin light chains were measured in the CSF of patients with neurological disorders. Results,,, A significant agreement was found between an increase in free kappa light chain CSF serum quotients and results of the currently widely applied method of oligoclonal band measurement for the detection of intrathecal immunoglobulin synthesis. A sensitivity of 95% and 100% specificity for free kappa light chain concentrations at a cut-off of 0.41 mg/l was determined for free kappa light chains compared with oligoclonal bands. However, the free lambda light chains in 20 out of the 110 investigated samples were characterized by inconsistent behaviour. These otherwise unremarkable samples yielded increased CSF quotients, leading to the assumption that free lambda light chains represent a highly sensitive measure of intrathecal immunologlobulin synthesis. Thirteen of the 20 samples described above were obtained from patients with cerebral infarction, 4 samples derived from patients with cerebral paresis (primarily facial paresis), one sample was from a patient with multisystem atrophy and two were obtained from patients with migraine and neuralgia. Conclusion,,, These findings suggest that the high sensitivity of lambda light chains for the detection intrathecal immunoglobulin synthesis may be of benefit in establishing clinical diagnoses. [source] | |||||||||||||