Signalling profiles of circulating leucocytes in patients recovered from reactive arthritis

• Published in: Scandinavian journal of rheumatology 2012-08, Vol.41 (4), p.267-274
• Main Authors: Alanärä, T, Aittomäki, S, Kuuliala, K, Kuuliala, A, Siitonen, S, Leirisalo-Repo, M, Repo, H
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Reactive - drug therapy; Arthritis, Reactive - immunology; Arthritis, Reactive - metabolism; Biological and medical sciences; Diseases of the osteoarticular system; Diseases of the spine; Female; HLA-B27 Antigen - immunology; HLA-B27 Antigen - metabolism; Humans; Inflammatory joint diseases; Infliximab; Leukocytes - drug effects; Leukocytes - immunology; Leukocytes - metabolism; Male; Medical sciences; Middle Aged; NF-kappa B - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Phosphorylation - immunology; Signal Transduction - drug effects; Signal Transduction - immunology; Yersinia enterocolitica - immunology; Yersinia Infections - immunology; Yersinia Infections - metabolism
• ISSN: 0300-9742; 1502-7732
• DOI: 10.3109/03009742.2012.664649

Objectives: Reactive arthritis (ReA) is a sterile joint inflammation triggered by a remote infection and associated with human leucocyte antigen (HLA)-B27. Its pathogenesis is unknown, but abnormal response to microbial structures or endogenous inflammatory mediators may be involved. We studied responses in leucocyte signalling profiles in patients with previous ReA after a full recovery. Method: The study comprised 10 HLA-B27-positive healthy subjects with a history of Yersinia enterocolitica-triggered ReA (B27+ReA+) and 20 healthy reference subjects, of whom 10 carried HLA-B27 (B27+ReA-) and 10 did not (B27-ReA-). Phosphospecific fluorescent monoclonal antibodies and flow cytometry were used to determine activation of nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STATs) 1, 3, 5, and 6, and two mitogen-activated protein (MAP) kinases, p38 and extracellular signal-regulated kinase (ERK)1/2, in monocytes, lymphocytes, lymphocyte subsets, and neutrophils. B27+ReA+ and B27-ReA- whole-blood samples were incubated with Yersinia with or without infliximab to study the role of tumour necrosis factor (TNF) in lymphocyte subset activation. Samples of the three subject groups were studied using soluble bacterial or endogenous stimuli. Fluorescence levels were determined as relative fluorescence units (RFU) and the proportion of positively fluorescing cells. Results: The intracellular activation of circulating leucocytes in response to soluble stimuli was consistently comparable in B27+ReA+, B27+ReA-, and B27-ReA- subjects. Infliximab inhibited Yersinia-induced lymphocyte NF-κB phosphorylation similarly in B27+ReA+ and B27-ReA- groups. Conclusions: ReA susceptibility is not reflected in leucocyte signalling profiles elicited by phlogistic stimuli. However, the possibility remains that aberrations occur in response to combinations of stimuli, such as those associated with leucocyte adhesion.