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Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune?related pancytopenia.

ABSTRACT: Immuno-related pancytopenia (IRP) is characterized by pancytopenia resulting from bone marrow suppression or destruction mediated by auto?antibodies. In our previous study, a K562 cDNA library was established, which was used to screen for seven possible auto?antigens produced by hematopoietic cells in patients with IRP, including ferritin light chain (FTL). In the present study, FTL was expressed and purified, and the levels of the auto?antibodies specific to FTL were measured. Through ELISA, it was shown that the titer of anti?FTL antibodies was higher in patients with IRP without treatment compared with those who had recovered from IRP, those with severe aplastic anemia (SAA), those with myelodysplastic syndrome (MDS) and the healthy controls. Furthermore, the expression levels of FTL?mRNA were upregulated in patients with IRP without treatment compared with those who had recovered from IRP, those with MDS and the normal controls. The results suggest that FTL antibody expression is upregulated in patients with IRP. Detecting FTL antibodies may therefore have certain clinical value in differentiating between IRP, SAA and MDS. Furthermore, in specific patients with IRP, FTL as an auto?antigen may induce immune attack on hematopoietic stem cells.

SUBMITTER: Hao S

PROVIDER: S-EPMC7411336 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune‑related pancytopenia.

Hao Shanfeng S Zhang Yang Y Hua Luogang L Xie Ning N Xiao Na N Wang Huaquan H Fu Rong R Shao Zonghong Z

Molecular medicine reports 20200626 3

Immuno-related pancytopenia (IRP) is characterized by pancytopenia resulting from bone marrow suppression or destruction mediated by auto‑antibodies. In our previous study, a K562 cDNA library was established, which was used to screen for seven possible auto‑antigens produced by hematopoietic cells in patients with IRP, including ferritin light chain (FTL). In the present study, FTL was expressed and purified, and the levels of the auto‑antibodies specific to FTL were measured. Through ELISA, it ...[more]

PMID: 32705249

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Project description:Sepsis-associated acute kidney injury (SA-AKI) is a key contributor to the life threatening sequalae attributed to sepsis. Mechanistically, SA-AKI is a consequence of unabated myeloid cell activation and oxidative stress that induces tubular injury. Iron mediates inflammatory pathways directly and through regulating the expression of myeloid-derived ferritin, an iron storage protein comprised of ferritin light (FtL) and ferritin heavy chain (FtH) subunits. Previous work revealed myeloid FtH deletion leads to a compensatory increase in intracellular and circulating FtL and is associated with amelioration of SA-AKI. We designed this study to test the hypothesis that loss of myeloid FtL and subsequently, circulating FtL will exacerbate the sepsis-induced inflammatory response and worsen SA-AKI. We generated a novel myeloid-specific FtL knockout mouse (FtLLysM-/-) and induced sepsis via cecal ligation and puncture or lipopolysaccharide endotoxemia. As expected, serum ferritin levels were significantly lower in the knockout mice, suggesting that myeloid cells dominantly contribute to circulating ferritin. Interestingly, while sepsis induction led to a marked production of pro- and anti-inflammatory cytokines, there was no statistical difference between the genotypes. There was a similar loss of kidney function, as evident by a rise in serum creatinine and cystatin C, and renal injury identified by expression of kidney injury molecule-1 and neutrophil gelatinase associated lipocalin. Finally, RNA sequencing revealed upregulation of pathways for cell cycle arrest and autophagy post-sepsis, but no significant differences were observed between genotypes, including in key genes associated with ferroptosis, an iron-mediated form of cell death. The loss of FtL did not impact sepsis-mediated activation of NFkB or HIF-1a signaling, key inflammatory pathways associated with dysregulated host response. Taken together, while FtL overexpression was shown to be protective against sepsis, loss of FtL did not influence sepsis pathogenesis.

Dataset Information

Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune?related pancytopenia.

Publications

Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune‑related pancytopenia.

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