Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are immune-mediated diseases, which share clinical features, but differ in the mechanisms, leading to aberrant immune responses. Natural killer (NK) cells tune the innate immune response depending on the integration of signals coming from a complex network of activating and inhibitory surface receptors. Here, we aim to elucidate the potential role of NK and T cells in inflammation and autoimmunity in RA and PsA and we focused on extensive characterization of the NK cell receptor (NKR) (co-) expression patterns on their surface.
Methods
The frequency of T and NK cells expressing Killer like immunoglobulin Receptors (KIR), NKG2 and Natural Cytotoxicity receptors was assessed by 10-color flow cytometry (FCM) in peripheral blood of 23 RA patients (ACR 1987 revised criteria), 12 PsA patients (Taylor et Al, 2006 Classification of Psoriatic Arthritis Study Group criteria for PsA) and 18 healthy controls (HC). Cytotoxicity of NK cells against K562 cells before and after stimulation with IL-12 and IL-18 as broad activating signals was assessed in a FCM-based cytotoxicity assay in 8 additional RA patients and 8 additional HC; during co-culture, NK degranulation was measured by cell surface expression of CD107a and IFNγ intracellular expression was also assessed in parallel.
Results
RA patients, but not PsA patients, had an increased frequency of NK cells expressing the inhibitory receptor NKG2A compared to HC, particularly in patients with rheumatoid factor positivity. The NKG2A+ NK population was predominantly CD56dimand lacked expression of KIRs and activating NKG2C. No differences were observed in the expression of the other NKRs between HC and RA nor PsA patients.
RA patients showed decreased cytotoxicity against K562 cells in the 10:1 Effector:Target ratio, when compared to HC, but the capability of killing in RA NK cells was restored after IL-12/IL-18 stimulation. Degranulation and IFNγ expression were similar in HC and RA patients.
T cells expressing the Fcγ receptor CD16 were more frequent in RA than in HC. Compared to HC, we found higher frequencies of T cells expressing the KIRs CD158ah in both RA and PsA, and CD158e1e2 in RA. CD4+T cells expressing the KIRs CD158ah, CD158b1b2j and CD158e1e2, although present at low frequency, were also significantly elevated compared to HC.
Conclusion
The differences in NKR expression on NK and T cells in RA and PsA could mirror the diverse pathogenic mechanisms implicated in these diseases; in particular, the immature phenotype (NKG2A+/KIR-) of circulating NK cells in RA and the reversible impairment in their cytotoxic ability could reflect the activation status of the NK population described in RA synovial fluid and provide growing evidence for the potential of the exploitation of NKG2A blockade in this disease.
Disclosure:
M. Cossu,
None;
S. T. van Bijnen,
None;
M. Roeven,
None;
T. Jansen,
Abbvie,
2,
UCB,
2,
Abbvie,
5,
AstraZeneca,
5,
UMS,
5,
Janssen Pharmaceutica Product, L.P.,
5,
Menarini,
5,
Novartis Pharmaceutical Corporation,
5,
Pfizer Inc,
5,
Roche Pharmaceuticals,
5,
Abbvie,
8;
F. Preijers,
None;
H. Dolstra,
None;
T. Radstake,
None.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/extensive-natural-killer-cell-receptor-phenotyping-on-nk-and-t-cells-discloses-differences-in-ra-and-psa-potentially-mirroring-diverse-immunoregulatory-functions/