Long-term clinical and biomarker observations following rituximab exposure in two siblings with CSF1R-related leukoencephalopathy: a preliminary familial case series.

Authors

Ramojus Balevicius, Lidija Marija Smertinaite, Mourad Kourie, Zbigniew Wszolek, Goda-Camile Mickeviciute, Robert Harris, Tobias Granberg, Nadezda Zhuravleva, Jinming Han, Virginija Danylaite Karrenbauer

Published in

Communications medicine. Volume 6. Issue 1. Sep 30, 2026. Epub Sep 30, 2026.

Abstract

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy (CRL) is a rare microgliopathy, characterized by progressive neurodegeneration. Impaired STAT3 signaling reduces microglial numbers and limits their ability to clear cellular debris, leading to persistent inflammation and brain tissue damage that activates peripheral CD20⁺ B cells. These cells migrate into the CNS and secrete interleukin-6 (IL-6), amplifying inflammation and further disrupting STAT3 signaling in a self-reinforcing cycle that drives white-matter injury.
We describe two siblings from a single family, both carrying the same heterozygous CSF1R variant (c.2562 T > A, p.Asn854Lys), who received four infusions of rituximab (RTX;500 mg) on a compassionate, off-label basis between 2014-2017. The long-term disease trajectory was evaluated using standardized clinical rating scales and brain magnetic resonance imaging (MRI). As a secondary biomarker outcome, serum and CSF neurofilament light chain (NfL) concentrations were assessed.
In both siblings, RTX exposure was followed by EDSS stability at 6.5 and 7.0, respectively, over 5 years, with mixed trajectories in other functional and cognitive domains. Over the 23-year MRI follow-up period, patients developed cerebral atrophy. During the post-treatment period, no new focal lesions were observed on brain MRI, and levels of CSF-NfL and CSF-CXCL13 were normalized.
In this preliminary familial case series of two siblings carrying the same CSF1R variant, RTX exposure was followed by long-term clinical stability and favorable biomarker trajectories. Patient 1 had a pre-treatment disease course of approximately 13 years, indicating an inherently slow disease progression that cannot be entirely separated from the treatment effect in an uncontrolled observation.

PMID:
42827143
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

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