The main objective of this study is to characterize the pathogenic B cells and the auto-antibodies that are responsible for causing the myasthenic or pemphigus syndromes. The secondary objective is to generate recombinant antibodies based on the…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective:
- To isolate PBMC from patients with AChR MG, MuSK MG, LEMS or pemphigus to
determine the pathogenic B cell receptor sequences.
Secondary outcome
Secondary Objective(s):
- To generate recombinant antibodies derived from pathogenic auto-antibodies
from AChR MG, MuSK MG, LEMS or pemphigus patients.
- To determine the phenotype of pathogenic antibody producing B cells.
- To correlate disease severity and other patient characteristics with
pathogenic antibody producing B cell numbers and B cell receptor sequences.
Background summary
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome are neuromuscular
autoimmune diseases hallmarked by fluctuating and fatigable muscle weakness.
These disorders are caused by auto-antibodies inhibiting the function of
acetylcholine receptors (AChR), muscle-specific kinase (MuSK) or voltage-gated
calcium channels (VGCC) respectively, which culminates in failure of
neuromuscular transmission and muscle weakness. Pemphigus is a group of skin
disorders in which antibodies are formed against desmosomes leading to blister
formation of mucosa and skin.
Pre-clinical studies currently depend on the availability of patient serum and
plasmapheresis material. Moreover, the auto-antibody response has only been
studied through indirect experimental approaches. Myasthenia gravis and
pemphigus share (immunological)_ disease features.
Study objective
The main objective of this study is to characterize the pathogenic B cells and
the auto-antibodies that are responsible for causing the myasthenic or
pemphigus syndromes. The secondary objective is to generate recombinant
antibodies based on the auto-antibody sequences identified. This would result
in an unlimited source of auto-antibodies for pre-clinical studies.
Study design
This is a prospective, single blood donation study.
Study burden and risks
Patients will be invited to participate in this study two weeks before their
regular outpatient clinical visit. When the patient consents to participate
they will undergo regular MG/pemphigus assessment to determine MG/pemphigus
severity. After the standard clinical assessment, 120mL of blood will be
withdrawn. Two tubes are part of the standard procedure for auto-antibody titre
and haematological and kidney and liver function testing. The remainder will be
used to isolate PBMC. One hundred twenty ml of blood withdrawal can be
considered safe as in a blood donation setting a 5 fold of blood volume is
withdrawn without significant risks for the donator. All procedures mentioned
for this protocol are part of the standard outpatient clinical visit except the
volume of blood that is withdrawn. The risk for the patients to participate in
this study is therefore considered low. The patient might benefit from this
study in the future as the proposed study might yield more insight in the
disease mechanism and facilitates pre-clinical therapeutic tests.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
For myasthenia gravis:
1. Males and females aged between 18 years and older at the time of the
blood donation.
2. Patient with ocular or generalized AChR MG, MuSK MG or LEMS; and
3. A positive serologic test for AChR antibodies > 0.5 nmol/l or MuSK
antibodies >0.1 nmol/l or VGCC antibodies >20 fmol/l. , For Pemphigus:
1. Males and females aged between 18 years and older at the time of the blood
donation.
2. Patient with pemphigus subtypes and
3. A positive serologic test for Dsg1 antibodies > 0.5 nmol/l or Dsg3
antibodies >0.1 nmol/l.
Exclusion criteria
For myasthenia gravis and pemphigus:
1. Any confirmed or suspected immunosuppressive or immunodeficient condition
not related to the treatment of MG, including human immunodeficiency virus
(HIV) infection, or a family history of congenital or hereditary
immunodeficiency.
2. History or evidence of administration of immunoglobulins within 1 month
prior to the blood withdrawal.
3. The investigator can exclude patients for this trial which are deemed not
suitable for any reason.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL60336.058.16 |