Immunoglobulin Measurement

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Frank Birklein - One of the best experts on this subject based on the ideXlab platform.

  • High sensitivity of free lambda and free kappa light chains for detection of intrathecal Immunoglobulin synthesis in cerebrospinal fluid.
    Acta neurologica Scandinavica, 2008
    Co-Authors: Borros M. Arneth, Frank Birklein
    Abstract:

    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.

Borros M. Arneth - One of the best experts on this subject based on the ideXlab platform.

  • High sensitivity of free lambda and free kappa light chains for detection of intrathecal Immunoglobulin synthesis in cerebrospinal fluid.
    Acta neurologica Scandinavica, 2008
    Co-Authors: Borros M. Arneth, Frank Birklein
    Abstract:

    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.

John M. Finke - One of the best experts on this subject based on the ideXlab platform.

  • Anti-aβ oligomer IgG and surface sialic acid in intravenous Immunoglobulin: Measurement and correlation with clinical outcomes in Alzheimer's disease treatment.
    PloS one, 2015
    Co-Authors: Hyewon Kwon, Amanda C. Crisostomo, Hayley Marie Smalls, John M. Finke
    Abstract:

    The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous Immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer’s Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.

Hyewon Kwon - One of the best experts on this subject based on the ideXlab platform.

  • Anti-aβ oligomer IgG and surface sialic acid in intravenous Immunoglobulin: Measurement and correlation with clinical outcomes in Alzheimer's disease treatment.
    PloS one, 2015
    Co-Authors: Hyewon Kwon, Amanda C. Crisostomo, Hayley Marie Smalls, John M. Finke
    Abstract:

    The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous Immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer’s Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.

Chang-ki Min - One of the best experts on this subject based on the ideXlab platform.

  • Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple myeloma.
    Clinica chimica acta; international journal of clinical chemistry, 2018
    Co-Authors: Hyojin Chae, Eunhee Han, Jaeeun Yoo, Jaewoong Lee, Jeong Joong Lee, Kyoungho Cha, Myungshin Kim, Yonggoo Kim, Sung-eun Lee, Chang-ki Min
    Abstract:

    Abstract Background The heavy-light chain (HLC) assay enables the accurate Measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC Measurements in the routine follow-up of intact Immunoglobulin multiple myeloma (MM) patients. Methods A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total Immunoglobulin Measurement, free light chain, and HLC assay. The correlations between M-protein levels and the HLC and FLC assay-derived parameters were examined and the clinical significance of the biomarkers was evaluated according to patients' status. Results Involved HLC (iHLC) was the best biomarker correlating with M-protein concentration in both IgG and IgA MM, and could provide a surrogate marker substituting M-protein levels to follow the course of the disease, especially in β-migrating IgA M-proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC) yielded significantly different results among the various response categories in both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC in a stringent complete remission (sCR) sample was a marker of early non-symptomatic relapse. Conclusion In this study of a cohort of 176 patients in a routine clinical setting, we have provided evidence of the clinical utility of real world HLC assays for the identification of M-proteins and to monitor M-proteins with an emphasis on IgA monoclonal gammopathies.