1) To study the effects of antibody removal by immunoadsorption on the immune phenotype over time in patients with B-cell related autoimmune diseases such as MG, AAV, anti-GBM disease, cryoglobulinemic vasculitis and other refractory antibody-…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Neuromuscular disorders
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the change in immune phenotype over time in
patients with B-cell mediated autoimmune disease, prior, and in response to
immune suppression and IA as part of their standard treatment. The course of
plasma levels of disease specific autoantibodies (e.g. anti-GBM, PR3- or
MPO-ANCA) will be monitored for 12 months on a regular basis. Moreover,
autoantibody typing (IgG isotypes, IgA, IgM) and characteristics (e.g.
glycosylation/galactosylation profiles) as well as characteristics of B- and
T-cells and plasma cell subsets, in-vitro profiles (e.g. PBMC activation and Ig
release) and antibody effector functions will be analysed before and during the
follow-up of this study. Clinical parameters and questionnaires will be
collected to correlate the clinical course with differences in the immune
phenotype. The results of antibody tests and cell subset data will be compared
between patients with the same disease and between different diseases. If
feasible such as in AAV, these data will be also compared to a matched disease
control group with a similar immunosuppressive therapy but without an
indication for add-on IA.
Secondary outcome
.
Background summary
Extracorporeal techniques for removal of pathogenic autoantibodies from a
patient*s plasma are widely used in severe forms of B-cell related autoimmune
diseases, including Myasthenia Gravis (MG), Anti-neutrophil cytoplasm antibody
(ANCA)-associated vasculitis (AAV), anti-glomerular basement membrane
(anti-GBM) disease and cryoglobulinemic vasculitis. The effects of antibody
removal on B-cells and plasma cells are unclear but it may alter the immune
composition, regulation and activity. The clinical response to immune-depleting
therapies, such as immunoadsorption (IA), is variable, and frequently
unpredictable. Better understanding of the dynamics of the immune system during
therapy is needed to improve tailor made and precise choice of therapy for
these immune-mediated disorders. This observational study is a part of the
*Target-to-B* consortium, which is a collaboration between academic centres to
investigate the role of the B-cell in human disease.
Study objective
1) To study the effects of antibody removal by immunoadsorption on the immune
phenotype over time in patients with B-cell related autoimmune diseases such as
MG, AAV, anti-GBM disease, cryoglobulinemic vasculitis and other refractory
antibody-mediated diseases.
2) To prospectively collect disease-specific (clinical) outcome parameters
according to the current standard clinical care protocols.
3) To evaluate immunological profiles or patterns in patient cohorts with the
same disease and to study differences in these patterns between different
auto-immune disease.
Study design
Multicenter, prospective, observational cohort study.
Study burden and risks
Patients will be treated according to the international standard of care for
the particular B-cell mediated autoimmune disease. Due to the observational
character of this study, the only extra burden and risk associated with
participation is due to additional blood and urine sampling as well as
questionnaires. Most of the blood samples will be scheduled during the routine
clinical follow-up as indicated in table 2. Notably, children above the age of
six with one of the above mentioned disease (especially MG, AAV, anti-GBM
syndrome or a refractory antibody-mediated disease) can be included as well.
The reasoning for this is that the pathogenic immune responses in these
diseases may be different in younger age compared to adult patients but the
standard of care therapeutic approach does not differ until now. Gaining
insights in the immune composition and responses during the treatment in
younger patients can therefore possibly help to understand and improve future
therapeutic options with respect to age. Besides this, the results of this
study will provide overall funda-mental insights in the dynamics of the immune
system and the role of the B-cell before, dur-ing and after therapy in all
patients with particular autoimmune-mediated disorders. In the future, the
results of this study will potentially benefit patients in terms of (age
matched) tailor-made and specific choices of therapies for these B-cell
mediated autoimmune diseases.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
following criteria:
#Patients with a new or previous diagnosis of:
* Anti-AChR or anti-MuSK Myasthenia Gravis
* MPO- or PR3-ANCA associated vasculitis
* Anti-GBM glomerulonephritis
* Cryoglobulinemia vasculitis with severe organ involvement
* Refractory and severe antibody-mediated diseases*
# Patients with an indication for plasma exchange or IA based on:
1. AChR or MuSK-positive MG with at least one of the following features:
- Insufficient clinical response to immunosuppressive therapy of severe
ocu-lar, bulbar or generalized muscle weakness.
- Exacerbation with severe bulbar or respiratory dysfunction.
2. MPO- or PR3-ANCA vasculitis defined at least by one of the following
features:
- Renal involvement indicated by renal biopsy and/or glomerular erythrocy-turia
WITH active glomerulonephritis and newly reported eGFR < 50 ml/min/1.73 m²
and/or rapidly deteriorating renal function.
- Pulmonary hemorrhage. Anti-GBM syndrome with at least one of the fol-lowing
features:
3. Anti-GBM syndrome with at least one of the following features:
- Anti-GBM glomerulonephritis proven by renal biopsy and/or urine sediment
suspecting active glomerulonephritis and newly reported eGFR < 50 ml/min/1.73
m² and/or rapidly deteriorating renal function.
- Pulmonary hemorrhage with anti-GBM autoantibodies (> 10 IU/ml).
- Serological evidence of circulating anti-GBM autoantibodies (> 10 IU/ml).
4. Cryoglobulinemia vasculitis with at least one of the following features:
- Symptomatic hyperviscosity syndrome.
- (Life-threatening) organ involvement (e.g. renal involvement (proven by renal
biopsy and newly reported eGFR < 50 ml/min/1.73 m² and/or rapidly deteriorating
renal function), pulmonary hemorrhage, progressive neuropa-thy).
- Severe, refractory cutaneous vasculitis.
5. Refractory antibody-mediated diseases
- This category may include autoimmune haemolytic anemia or other anti-body
positive B-cell mediated autoimmune diseases.
- Based on case-based peer review between the investigators, patients with rare
refractory antibody-mediated diseases can be considered for inclu-sion. In case
of paediatric patients, additional reviewing by the paediatric immunologist
involved in the *Target-to-B* consortium (Prof. dr. T. Kuijpers) can be
obtained before inclusion.
Exclusion criteria
- Pregnancy at time of study entry.
- Previously reported allergic reactions to the immunosuppressive therapies or
IA.
- Plasmapheresis or IA within 3 months before inclusion.
- Intravenous immunoglobulin within 3 months before inclusion.
- Patients aged < 6 years.
- Treatment with >7 days of oral cyclophosphamide or >1 IV dose of
cyclophos-phamide within 3 months prior to inclusion and/or >7 days of
predni-sone/prednisolone (>30 mg/day or > 1 mg/kg/day in paediatric patients)
within 1 month prior to inclusion expect for patients with MG and/or >1 dose of
rituximab within 9 months prior to inclusion.
Design
Recruitment
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 | NL70185.068.19 |