Effekt einer Interleukin-1-Blockade auf klinische und laborchemische Parameter bei Patienten mit Cryopyrin-Assoziiertem Periodischen Syndrom (CAPS) mit Schwerpunkt auf dem renalem Outcome
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Philipps-Universität Marburg
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Abstract
Autoinflammatory syndromes (AIS) are orphan diseases characterized by chronic inflam-
mation, presenting with fever, arthralgia and often urticaria. They are the result of a ge-
netic alteration of the inflammasome, often with an increased production of interleukin-
1 (IL-1). The Cryopyrin-associated periodic syndrome (CAPS) consists of a specific
group of AIS, usually having a mutation in the NLRP3 gene and presenting with a variety
of clinical signs and symptoms. Current therapies address the inflammatory cascade by
interfering with IL-1 pathways, leading to clinical remission and reduction of inflamma-
tion in most patients. While some CAPS patients develop AA amyloidosis with chronic
kidney disease (CKD), the effect of anti-IL-1-therapy on renal outcome remains unclear.
The objective of this retrospective study was to investigate the efficacy of anti-IL-1 thera-
py on clinical symptoms and inflammatory parameters with special focus on renal out-
come. Patients from the outpatient clinic at the Department of Internal Medicine, Neph-
rology & Intensive Care Medicine, Philipps-University Marburg, with positive Eurofe-
ver-criteria for CAPS and/or a proven mutation, which were treated with anakinra or can-
akinumab, were examined. A total of 28 CAPS patients at a medium age of 31,3±12,2
years were studied, 14 were followed-up for 9.7 years. 21 patients showed a mutation in
the NLRP3 gene, 17 individuals were related and members of 4 families. Patients with
the so-called „low-penetrance“ mutation p.Q703K were similarly affected with respect to
clinical presentation and inflammatory parameters. Five patients (24%) of different ages
and carriers of the most common mutation R260W had significant chronic kidney disease
at the time of therapy initiation. All five patients were related to each other, while other
family members with the same mutation had no CKD. Two of them had AA-amyloidosis
and were excluded from the study regarding the effectiveness of therapy, because one
patient required dialysis and the other patient received an allogeneic kidney transplant
due to terminal renal insufficiency requiring dialysis. Anti-IL-1 therapy led to reduced
clinical symptom burden and significantly lower inflammatory parameters in the other
three patients examined; Only two of the three patients with relevant kidney damage
showed persistent proteinuria, which in one patient had completely regressed at the end
of the observation period. Patients without pre-existing kidney damage did not develop
any relevant impairment of kidney function under IL-1 blockade.
In conclusion, we showed that in patients with CAPS: (1) CDK is a relatively frequent
complication with around 24%; (2) renal manifestation beyond the mutation status in the NLPR3 gene apparently requires a further predisposition and is independent of age; (3)
anti-IL-1 therapy leads to a significant improvement of inflammatory parameters and
symptom load, which do not strictly correlate with each other; and (4) may prevent de-
velopment of CAPS-associated CKD but not affect pre-existing renal damage. Our data
suggest that early therapy initiation might sufficiently improve renal disease progression.
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Created: 2024Issued: 2025-02-26Updated: 2025-02-26
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
DFG-subjects
renales OutcomeCanakinumabAutoinflammatorische SyndromeAnakinraCAPSCryopyrin-Assoziiertem Periodischen SyndromPeriodische Fiebersyndrome,
DDC-Numbers
610
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Johannsen, Sophia; : Effekt einer Interleukin-1-Blockade auf klinische und laborchemische Parameter bei Patienten mit Cryopyrin-Assoziiertem Periodischen Syndrom (CAPS) mit Schwerpunkt auf dem renalem Outcome. : Philipps-Universität Marburg 2025-02-26. DOI: https://doi.org/10.17192/z2025.0144.