Signalling profiles of circulating leucocytes in patients recovered from reactive arthritis.
OBJECTIVE
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.


METHODS
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.
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
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T
Alanärä
S
S
Aittomäki
K
K
Kuuliala
A
A
Kuuliala
S
S
Siitonen
M
M
Leirisalo-Repo
H
H
Repo
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016918:Arthritis, Reactive / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015796:HLA-B27 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D000091402:Prohibitins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology* / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015796:HLA-B27 Antigen; D016328:NF-kappa B; C000717331:PHB2 protein, human; D000091402:Prohibitins; D000069285:Infliximab; D048051:p38 Mitogen-Activated Protein Kinases