Biochemical analysis reveals aberrant and variable Immunoglobulin M composition in Waldenström macroglobulinemia and IgM monoclonal gammopathy of unknown significance
Bibliographic record
Abstract
Waldenström Macroglobulinemia (WM) is a rare B cell malignancy defined by greater than 10% infiltration of lymphoplasmacytic cells in the bone marrow (BM) and a circulating monoclonal Immunoglobulin M (IgM), while its precursor state IgM monoclonal gammopathy of undetermined significance (MGUS) has <10% BM infiltration. WM and IgM MGUS are unique amongst malignant lymphomas because symptoms and treatment indication may be caused by monoclonal IgM and not by the malignant cell infiltration. These symptoms correlate poorly with IgM levels, suggesting there may be specific biochemical properties of those pathological IgMs, yet IgM structure in IgM gammopathies has not been systematically studied. In healthy individuals, IgM circulates as a pentameric molecule that consists of five covalently linked monomers (H2L2 pairs), a joining (J-) chain and one CD5-Like (CD5L) molecule. In order to gain insight into structural variation of IgM in monoclonal IgM gammopathies, we developed and tested several assays to determine J-chain and CD5L content and polymerization state of IgM from 29 IgM MGUS and WM patients. In multiple cases, IgM was found to be (partially) devoid of J-chain, which associated with differential assembly of IgM into variably sized polymers. Moreover, we found that IgM exceeding ~5 g/L was no longer saturated with CD5L. Relative binding of polymeric Ig receptor varied by over 30-fold. Combined, in this pilot study we demonstrate that structural and functional variation in IgM of IgM MGUS and WM is common. These aberrations in IgM structure may relate to variations in clinical phenotype in IgM monoclonal gammopathies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".