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Clinical and Translational Medicine
Fig. 3 | Clinical and Translational Medicine

Fig. 3

From: The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis: a case report

Fig. 3

IL-6 production by blood leukocytes is altered in the RA-like PsoA patient in response to immune activators. In healthy individuals (top panel), the stimulation of peripheral blood mononuclear cells with immune activators leads to the activation of intracellular multiprotein oligomers (e.g. inflammasomes) and specific receptors that activate signalling pathways, including TRAF proteins, translocation of transcription factors and subsequent cytokine response. In the patient with aggressive RA-like PsoA (bottom panel), the activation of blood cells with anti-CD3 + anti-CD28, pro-inflammatory cytokines IL-1β, TNF and IFN-γ, muramyl dipeptide (MDP), lipopolysaccharide + adenosine triphosphate (LPS + ATP) and poly(deoxyadenylate–thymidylate) [poly(dA:dT)] led to a unique overproduction of IL-6 (red arrows). As the patient is a heterozygous carrier for a single nucleotide polymorphism p.Asp10Asn (p.D10N) in TRAF3IP2, this susceptibility allele causes altered TRAF6 binding (double red lines with an oblique stroke). The inhibition of the TRAF6 pathway could upregulate the TRAF2/5 pathway, leading to an enhanced immune response [21, 22] (dashed red arrow)

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