Disease Information

General Information of the Disease (ID: DIS00393)

• Name: Autoimmune disease
• ICD: ICD-11: 4A4Z

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Abatacept

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Aldehyde dehydrogenase 1A1 (ALDH1A1) [1]

• Resistant Disease: Autoimmune disease [ICD-11: 4A4Z.0]
• Resistant Drug: Abatacept
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Th17-mediated EAD model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Abatacept-resistant memory Th17 cells exhibit genes for aldehyde dehydrogenases. Memory-phenotype pTh17 cells exhibit a unique metabolic pathway that may involve ALDH for both survival and function.

Melatonin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Monocyte chemotactic and activating factor (CCL2) [2]

• Resistant Disease: Autoimmune disease [ICD-11: 4A4Z.0]
• Resistant Drug: Melatonin
• Molecule Alteration: Down-regulation; Expression
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Knockdown assay
• Mechanism Description: The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

References

• Ref 1: Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition. iScience. 2023 Dec 9;27(1):108646.
• Ref 2: Melatonin and inflammation-Story of a double-edged bladeJ Pineal Res. 2018 Nov;65(4):e12525. doi: 10.1111/jpi.12525. Epub 2018 Oct 12.