Fig. 5: Toll-like receptor stimulation analysis in Paediatric acute neuropsychiatric syndrome patients compared to controls.

A The Toll-like receptor (TLR) pathway is a crucial component of the innate immune system responsible for detecting and responding to various pathogens. TLR proteins expressed on immune cells recognize pathogen-associated molecular patterns like lipopolysaccharide (LPS), triggering a signaling cascade that produces pro-inflammatory cytokines, such as interleukin (IL)6 and tumour necrosis factor (TNF). TLR4= Toll-like receptor 4, TIRAP= Toll/interleukin-1 receptor (TIR) domain-containing adaptor protein, TRIF = TIR-domain-containing adaptor-inducing interferon-beta, TRAM = TRIF-related adaptor molecule, MyD88= myeloid differentiation primary response protein 88, IRAK= interleukin-1 receptor associated kinase, NF-κB (nuclear factor kappa light chain enhancer of activated B cells). B Gene expression and cytokine production of LPS stimulated peripheral blood mononuclear cells (PBMCs) of PANS patients compared to controls. PBMCs of PANS and controls were stimulated with 500 ng/mL LPS for 30 min, 3 h, and 24 h. Gene expression of IL6, and TNF were measured using quantitative reverse transcription polymerase chain reaction. Target gene expression was normalized to household gene, Beta-2-Microglobulin. In addition, release of IL6 and TNF into the cell culture media was measured using ELISA. C In PBMCs stimulated with LPS, IL6 gene (RNA) expression was lower at both 30 min (p < 0.05) and 3 h (p < 0.05) in PANS compared to controls, and IL6 and TNF protein production (ELISA) was significantly reduced at 3 h (p < 0.01) in PANS compared to controls (Fig. 5C). Bars and whiskers represent median with interquartile range; n = 7. Mann-Whitney test, *P < 0·05, **P < 0·01.