Investigating the Pathogenic Role of N-glycosylation in AL Amyloidosis: Molecular Bases, Diagnosis, and Treatment
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: AL Amyloidosis, MGUS, Multiple Myeloma, Monoclonal Gammopathies. Basic parameters: 18 years — 99 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Immunoglobulin light chain (AL) amyloidosis is caused by a typically small, minimally proliferating bone marrow plasma cell clone secreting a patient-unique, unstable, aggregation-prone, toxic light chain (LC). The amyloidogenicity of LCs is encrypted in their sequence, yet molecular determinants of LC pathogenicity remain obscure. N-glycosylation has been long suspected to be a determinant of LC amyloidogenicity based on anecdotal reports of individual AL patients with a clonal LC displaying this post-translational modification. It is hypothesized that N-glycosylation fundamentally contributes to determining the amyloidogenicity of immunoglobulin LCs in a subset of patients with AL and might influence its clinical phenotype. It is further proposed that the synthesis and secretion of unstable LCs that also have to be N-glycosylated might reverberate on the biology of the plasma cell clone, possibly modulating the sensitivity toward different drugs and might represent itself a therapeutic target. The objective of our study is now to elucidate the molecular role of LC N-glycosylation in AL amyloidosis, exploit it for risk assessment, and define its potential impact on the biology of the underlying plasma cell clone and its drug sensitivity.
Primary outcome measures
- Dataset of full-length LC variable region sequences [Time frame: two years]
Secondary outcome measures (3)
- Clinical correlates of LC N-glycosylation [Time frame: two years]
- Refinement of sequence-based prediction of LC amyloidogenicity [Time frame: two years]
- Biologic and pharmacologic correlates of LC N-glycosylation [Time frame: two years]
Eligibility criteria
Inclusion criteria
- Diagnosis of monoclonal gammopathy (e.g. AL amyloidosis, MGUS, MM, others)
- Planned peripheral blood sampling +/- bone marrow aspiration
- Age > 18 years
- Willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes through signing a written informed consent.
Exclusion criteria
- Lack of monoclonal gammopathy
- Patients fulfilling the criteria for complete hematologic response after anti-clonal therapy
- Age <18 years
- Failure to show willingness to allow use of clinical data and diagnostic leftovers of clinical specimens for research purposes.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Italy · 1 center
- Fondazione IRCCS Policlinico San Matteo di Pavia — Pavia
Identifiers
NCT: NCT07448779 · 2023-1731-GlycAL