The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis

Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of...

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Published in:	BMC musculoskeletal disorders Vol. 24; no. 1; p. 396
Main Authors:	Tan, Dino B A, Tedja, Chantalia, Kuster, Lukas, Raymond, Warren D, Harsanyi, Andreea, Chowalloor, Priya V, Misso, Neil L, Argawal, Shashi, Bhoola, Kanti D, Keen, Helen I
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 18-05-2023 BioMed Central BMC
Subjects:	Analysis Arthritis Arthritis, Rheumatoid - diagnosis Biomarkers Biomarkers - metabolism Blood Bradykinin Bradykinin receptors Development and progression Enzyme-linked immunosorbent assay Gout Gout - diagnostic imaging Health aspects Humans Hypertrophy Immunocytochemistry Inflammation Interleukin 12 Interleukin 6 Interleukin 8 Interleukin-6 - metabolism Kallikrein Kallikrein-kinin Kallikreins Kallikreins - analysis Kallikreins - metabolism Kininogens Kinins Kinins - analysis Kinins - metabolism Knee Laboratories Leukocytes Leukocytes (neutrophilic) Molecular weight Neutrophil Neutrophils Osteoarthritis Osteoarthritis - metabolism Pain Pain - metabolism Patient assessment Patients Phenotype Phenotypes Plasma Plasma levels Proteins Quality of Life Questionnaires Rheumatism Rheumatoid arthritis Rheumatology Synovial Fluid - metabolism Therapeutic targets Ultrasonic imaging Australia United States > US Biomarkers Arthritis Inflammation Neutrophil Bradykinin Kallikrein-kinin
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Summary:	Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1β, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2474 1471-2474
DOI:	10.1186/s12891-023-06388-9