Activation-dependent immune dysfunction traits enable identification of prodromal Parkinson's

A kit to diagnose if a subject is at risk of developing Parkinson's disease (PD), comprising:

• i. at least one antibody detecting at least one of cytokines selected from TNF, IL-1β, IL-2, IL-6, IL-8, and IL-10, and antibodies conjugated with electrochemiluminescence or fluorescence labels (secondary antibodies) against cytokine antibody;
• ii. at least one electrochemiluminescence or fluorescence conjugated antibody detecting T cells, selected from Table 2;
• iii. at least one electrochemiluminescence or fluorescence conjugated antibody detecting monocytes, selected from Table 3;
• iv. CD3/CD28 coated magnetic beads and human IFNγ;
• v. fluorescent agent staining the mitochondria and fluorescent agent staining the mitochondria with negative membrane potential;
• vi. fluorescent agent staining the lysosome and fluorescent agent indicating cathepsin activity;
• vii. leucine-rich repeat kinase 2 (LRRK2) antibody with or without electrochemiluminescence or fluorescence label, pT73 Rab10 antibody with or without electrochemiluminescence or fluorescence label, and electrochemiluminescence or fluorescence conjugated antibodies (secondary antibodies) against LRRK2 antibody or pT73 Rab10 antibody;
• and
• viii. PBS, MACS buffer, FACS buffer.

A method of treating a patient at risk of developing Parkinson's disease (PD), the method comprising administering a PD therapy, wherein the patient at risk exhibits increased ex vivo IFNγ stimulation-evoked cytokine secretion of TNF, IL-1γ, and IL-8 from monocytes, and at least one of the following:

• i. increase or decrease of monocyte subtype_or T cell subtype_when monocytes are ex vivo IFNγ stimulated or T cells are ex vivo CD3/CD28 stimulated;
• ii. decrease of ratio of mitochondria with negative membrane potential to total mitochondria in CD8+T cells when monocytes are T cells are ex vivo CD3/CD28 stimulated;
• increase or decrease of lysosome quantity and/or lysosome cathepsin activity in monocytes when monocytes are ex vivo IFNγ stimulated or CD8+ T cells when monocytes are T cells are ex vivo CD3/CD28 stimulated;
• or
• iv. increase of LRRK2 activity in monocytes when monocytes are ex vivo IFNγ stimulated.