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Immunology of bone marrow CD34 subsets and clonal hematopoiesis of indeterminate potential in amyotrophic lateral sclerosis
ИМУНОЛОГИЈА CD34 СУБПОПУЛАЦИЈА КОШТАНЕ СРЖИ И КЛОНАЛНА ХЕМАТОПОЕЗА НЕОДРЕЂЕНОГ ПОТЕНЦИЈАЛА У АМИОТРОФИЧНОЈ ЛАТЕРАЛНОЈ СКЛЕРОЗИ
- Часопис
- Serbian Archives of Medicine
- Објављено
- Srp Arh Celok Lek. 2025;153(11–12):575–583.
- Врста рада
- ORIGINAL ARTICLES
Abstract
Introduction Recent advances in pathogenesis of neurodegenerative diseases have shown that inflammation is a key factor of progression.
Methods The amyotrophic lateral sclerosis (ALS) group included 10 patients [mean age 55.1 ± 3.1 years (CI 95%: 48–62.2)]. Whole-exome sequencing and immunophenotyping of CD34+ subsets in bone marrow (BM) cells were performed before the start of therapy (baseline) and six months later (follow-up). The control group included 10 healthy donors, mean age was 39.9 ± 3.9 years (CI 95%: 31.2–48.6).
Results The peripheral blood stem cells (PBSCs) were collected after four-day granulocyte colony-stimulating factor administration. The total mean number of collected CD34+ cells was 290.4 ± 53.5 × 10⁶ (CI 95%: 177.6–403.3). Patients received fludarabine 25 mg/m²/day, on days one and two. To induce hematopoietic stem cell transdifferentiation the PBSCs were incubated with human placenta double-stranded DNA fragments ex vivo and reinfused 48 hours post fludarabine. Clonal hematopoiesis of indeterminate potential (CHIP) was detected in three cases (30%) before therapy. A significant increase CD34+CD13+ and CD34+CD123+ hematopoietic stem cells (HSCs) in BM was detected. The CD34+CD44+ level significantly decreased. Levels of CD34+CD7+, CD34+CD2+ and CD34+CD56+ showed a trend toward increased mean value after treatment. In two cases CHIP disappeared, in one case a decrease in the allelic variant frequency has been shown. The mean amyotrophic lateral sclerosis functional rating scale-revised score did not change [39 ± 0.6 points (CI 95%: 37.6–40.4) vs. 40.4 ± 0.7 (CI 95%: 38.8–42)].
Conclusion Our study is the first attempt to characterize the subsets of BM HSCs in ALS. They demonstrate that BM is able to respond to immune-mediated neuroinflammation. Preliminary results indicate a possible link between CHIP and ALS and point the way to eliminating aberrant clones.
Keywords: CD34 subsets; bone marrow; amyotrophic lateral sclerosis; clonal hematopoiesis of indeterminate potential; fludarabine