Scientists zero in on 2 proteins as potential treatment targets in ITP
DNAJC21, RNF5 may guide precise therapies for autoimmune disorder
Scientists in China have discovered that the proteins RNF5 and DNAJC21 — the latter encoded by the DNAJC21 gene — may be useful targets for developing new treatments for immune thrombocytopenia (ITP).
That’s according to a new analysis of genetic and protein data in ITP, for which the research team noted “the need for novel therapeutic targets.”
“This is the first study to demonstrate the involvement of both DNAJC21 and RNF5 in ITP at both gene and protein levels,” the researchers wrote. “Collectively, these findings not only deepen our understanding of ITP [disease development] but also provide a valuable resource for future biomarker discovery and therapeutic development.”
Their study, “Protein and gene levels of DNAJC21 and RNF5 as drug targets for immune thrombocytopenia: optimized post-GWAS insights,” was published in the journal Hematology.
ITP is a rare autoimmune disorder in which the immune system attacks and destroys platelets, which are cell fragments that help blood to clot. The resulting low platelet levels can give rise to symptoms like easy and prolonged bleeding or bruising.
Lack of reliable biomarkers as targets for ITP treatment
Biomarkers are proteins or other biological molecules that can be measured to give objective information about disease processes. Often, proteins identified as biomarkers for a given disease are found to be useful targets for treatment. But finding reliable biomarkers or treatment targets in ITP has been a challenge.
“Current international guidelines [for ITP care] emphasize the lack of diagnostic and prognostic biomarkers, limited evidence to guide treatment decisions, and highly variable therapeutic responses among patients. These limitations highlight the urgent need to identify novel molecular targets to improve disease understanding and therapeutic precision,” the researchers wrote.
To search for ITP biomarkers, the team conducted an optimized post-genome-wide association, or GWAS. This type of analysis basically looks at genetic variations: If a particular variation is significantly more common in people with a disease relative to those without, then there’s a good chance that genetic variation is associated with the disease.
The researchers’ analysis also used data on protein levels and function to assess how the proteins encoded by different genes may play roles in biological processes relevant to ITP.
“Our optimized post-GWAS framework improves the reliability and precision of identifying drug targets with ITP-associated … profiles,” the team wrote.
Current international guidelines [for ITP care] emphasize the lack of diagnostic and prognostic biomarkers, limited evidence to guide treatment decisions, and highly variable therapeutic responses among patients. These limitations highlight the urgent need to identify novel molecular targets to improve disease understanding and therapeutic precision.
These analyses zeroed in on two proteins, DNAJC21 and RNF5. Data indicated that high levels of DNAJC21 were associated with increased ITP risk, whereas higher levels of RNF5 were linked to a lower ITP risk. Similar associations with ITP risk were also seen with levels of each gene’s activity.
“Our study demonstrates that both DNAJC21 gene and protein are associated with ITP, potentially due to a single-point mutation or environmental factors that elevate protein [activity],” the scientists wrote. As for RNF5, the team noted that, “given the established link between viral infections and ITP, RNF5 downregulation [lower levels] could [contribute] to increased ITP susceptibility in virus-infected individuals. However, further investigation is needed to clarify the underlying mechanisms.”
Functional analyses indicated that both of these proteins help to control platelet levels in the body, lending credence to the idea that they may play a role in ITP.
The researchers concluded that DNAJC21 and RNF5 both may be viable treatment targets in ITP, though they highlighted a need for additional studies to validate these findings. As a particular limitation, the team noted that the datasets used in these analyses only contained data from people of European ancestry. Thus, their conclusions may not be applicable to non-European populations.
Still, “these findings provide novel mechanistic insights and identify DNAJC21 and RNF5 as promising therapeutic targets for ITP,” the team concluded.
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