CD4+T cells in chronic autoantigenic stimulation in MGUS, multiple myeloma and Waldenström's macroglobulinemia

2015 ◽  
Vol 137 (5) ◽  
pp. 1076-1084 ◽  
Author(s):  
Frank Neumann ◽  
Michael Pfreundschuh ◽  
Klaus D. Preuss ◽  
Claudia Schormann ◽  
Carsten Zwick ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Cd4 T Cells ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

scholarly journals Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia

2016 ◽  
Vol 23 (4) ◽  
pp. 379-385 ◽  
Author(s):  
Johanna Karlsson ◽  
Lucy Roalfe ◽  
Harriet Hogevik ◽  
Marta Zancolli ◽  
Björn Andréasson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Elderly Subjects ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Waldenström’S Macroglobulinemia ◽  
Control Subjects ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

ABSTRACTPatients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r= −0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r= 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

Accumulation of Inherited and Acquired Mutations in Hyaluronan Synthase1 Gene May Contribute Oncogenesis in Multiple Myeloma and Waldenstrom’s Macroglobulinemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3432-3432
Author(s):  
Sophia Adamia ◽  
Jennifer Hodges ◽  
Patrick M. Pilarski ◽  
Steven Treon ◽  
Michael J. Mant ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cells ◽  
Hematopoietic Cells ◽  
Genetic Variations ◽  
Waldenström’S Macroglobulinemia ◽  
Aberrant Splicing ◽  
Healthy Donors ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract In multiple myeloma (MM) and Waldenstrom’s macroglobulinemia (WM), we identified three alternatively and/or aberrantly spliced HAS1 transcripts—HAS1Va, HAS1Vb and HAS1Vc. Statistical analysis of samples taken from 172 untreated MM patients showed that expression of HAS1Vb, an intronic splice variant, strongly correlates with poor survival (P=0.005). We investigated the molecular basis of intron retention during HAS1 splicing in MM and WM patients. We speculated that aberrant HAS1 splicing and the associated reduced survival of MM patients, resulted from an accumulation of mutations in aberrantly spliced regions of HAS1. Exons and introns 3 and 4 of the HAS1 gene were sequenced, because they are hotspots for splicing aberrations. Sequencing of HAS1 was performed for a total 11 patients with WM and MM and 2 healthy donors. HAS1 gene templates for sequencing were isolated from a multiple sorted cell subpopulations, including malignant B and plasma cells (PC), non-malignant T cells and buccal epithelial cells (BECs), as well as hematopoietic progenitor cells (HPCs) from mobilized blood of MM patients. We detected sets of inherited and acquired genetic variations in HAS1 that were recurrent within 5–11 of the MM and WM patients analyzed, but absent from healthy donors. We also identified genetic variations that were unique to individual patients. Those HAS1 mutations found in all cell types tested, including BECs and from the hematopoietic cells (B, PC, T and HPCS) were classified as germline mutations. Those mutations found in hematopoietic cells but absent from BECs were classified as hematopoietic origin which acquired during the lifetime of the individual. Mutations identified only in malignant MM and WM B cells and PCs (absent from T cells, HPCs and BECs) were classified as acquired tumor specific mutations. Recurrent HAS1 mutations were found among both inherited and acquired sets of mutations. Some recurrent HAS1 mutations were common to both MM and WM. The high frequency of inherited HAS1 mutations suggests that they confer predisposition for developing MM or WM. Our sequencing analysis suggests that in MM and WM, sequential accumulation of genetic variations occurs as hematopoietic cells differentiate. Our data also suggest that hematopoietic origin mutations are necessary but by no means sufficient to drive HAS1 gene splicing. Effects of hematopoietic origin mutations on HAS1 splicing are manifested in malignant MM cells in context of additional tumor specific mutations, which are acquired by circulating B cells and passed to their plasma cell progeny. This suggests that mutations which lead to aberrant splicing of HAS1 pre-mRNA undergo mutational selection events, and leave a mutational “trace” throughout the hematopoietic cell lineage, including tumor cells. Existence of same mutational events detected in HAS1 gene from MM and WM supports the speculation that the precursors of both diseases may undergo a series of shared genetic events, diverging only when tumor specific mutations accumulate in distinct subsets of B lineage cells. In silico comparison of splicesomal assembly between wild type and mutated HAS1 gene gave a pattern that precisely predicts partial retention of intron and aberrant splicing of the HAS1 gene.

Calorimetric markers for monitoring of multiple myeloma and Waldenström’s macroglobulinemia patients

2018 ◽  
Vol 47 (5) ◽  
pp. 549-559 ◽  
Author(s):  
Svetla Todinova ◽  
Sashka Krumova ◽  
Avgustina Danailova ◽  
Violeta Petkova ◽  
Margarita Guenova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Waldenström’S Macroglobulinemia ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia
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