Profound invariant natural killer T-cell deficiency in inflammatory arthritis

Tudhope, Susan J.; Delwig, Alexei von; Falconer, Jane; Pratt, Arthur G.; Woolridge, T. D.; Wilson, Gillian; Isaacs, John D.; Ng, Wan‐Fai

doi:10.1136/ard.2009.125849

Cited by 28 publications

(32 citation statements)

References 36 publications

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“…In our study, we measured iNKT cell frequencies in seven patients before and after initiating methotrexate therapy and found that iNKT frequency increased as early as two weeks after the start of treatment. Unlike Parietti et al's results however, we found no obvious link to clinical response (Tudhope et al, 2010). Kojo et al (2001) examined the functional phenotype of Vα24Jα18 + DN iNKT cells in patients with RA and other autoimmune diseases.…”

Section: Inkt Cell Subsetscontrasting

confidence: 51%

“…Our own group analysed the frequency of Vα24 + Vϐ11 + NKT cells among 46 RA and 22 healthy controls, taking care to use a statistically robust minimum number of lymphocytegated events set at 500,000 in order to reliably measure the infrequent iNKT cells. Our results showed that RA patients have a 15-fold lower iNKT cell relative frequency compared to healthy controls (0.001% vs 0.21%, respectively), either before or after commencing immunosuppressive treatment (Tudhope et al, 2010).…”

Section: Peripheral Blood Compartmentmentioning

confidence: 74%

“…Whilst Yanagihara et al (1999) found no correlation between iNKT cell frequency and clinical disease activity, Parietti et al (2010) noted a trend toward lower iNKT cell numbers with higher disease activity (DAS28), ESR and CRP. Our group also found no correlation with disease activity although a moderate but statistically significant inverse relationship with CRP could be demonstrated (Tudhope et al, 2010). Parietti et al (2010) measured iNKT cell frequencies in seven patients before and after treatment with rituximab, an anti-CD20 monoclonal antibody targeting B cells.…”

Section: Inkt Cell Subsetsmentioning

confidence: 99%

“…In keeping with these earlier results, our own experiments showed that peripheral iNKT cells stimulated with α-GalCer for 12 days display impaired expansion in RA patients compared to controls (31 vs 121 fold, respectively). Using the 25 th percentile of foldexpansion in healthy controls, 75% of RA vs 20% of healthy controls are non-responders with no detectable differences between early and late RA (Tudhope et al, 2010). While investigating the mechanism underlying non-response to α-GalCer in RA patients, Kojo et al (2001) found that non-responder APCs could expand responder iNKT cells in the presence of α-GalCer and IL-2, albeit with a lower response than responder APCs.…”

Section: Inkt Cell Subsetsmentioning

confidence: 99%

See 3 more Smart Citations

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

Sowden¹,

Ng²

2012

Rheumatoid Arthritis - Etiology, Consequences and Co-Morbidities

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Section: Inkt Cell Subsetscontrasting

confidence: 51%

Section: Peripheral Blood Compartmentmentioning

confidence: 74%

Section: Inkt Cell Subsetsmentioning

confidence: 99%

Section: Inkt Cell Subsetsmentioning

confidence: 99%

See 2 more Smart Citations

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

Sowden¹,

Ng²

2012

Rheumatoid Arthritis - Etiology, Consequences and Co-Morbidities

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“…Therefore, NKT cells have been implicated in the control of autoimmune diseases, cancer, and infectious diseases (16). Our previous studies and those by other groups have demonstrated numerical and functional deficiencies of NKT cells in autoimmune diseases (17)(18)(19)(20). Although MAIT and NKT cells exclusively share the expression of the transcription factor PZLF (ZBTB16), emphasizing a close lineage relationship between these two distinct subsets, MAIT cell ontogeny is clearly different from NKT cells (5,21,22).…”

mentioning

confidence: 96%

Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Cho

Kee

Kim

et al. 2014

The Journal of Immunology

147

165

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Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide–stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.

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Natural killer T cell deficiency in active adult‐onset Still's disease: Correlation of deficiency of natural killer T cells with dysfunction of natural killer cells

Lee¹,

Cho²,

Kim³

et al. 2012

Arthritis & Rheumatism

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Objective. To examine the levels and functions of natural killer (NK) and natural killer T (NKT) cells, investigate relationships between NK and NKT cells, and determine the clinical relevance of NKT cell levels in patients with adult-onset Still's disease (AOSD).Methods. Patients with active untreated AOSD (n ‫؍‬ 20) and age-and sex-matched healthy controls (n ‫؍‬ 20) were studied. NK and NKT cell levels were measured by flow cytometry. Peripheral blood mononuclear cells were cultured in vitro with ␣-galactosylceramide (␣GalCer). NK cytotoxicity against K562 cells and proliferation indices of NKT cells were estimated by flow cytometry.Results. Percentages and absolute numbers of NKT cells were significantly lower in the peripheral blood of AOSD patients than in that of healthy controls. Proliferative responses of NKT cells to ␣GalCer were also lower in patients, and this was found to be due to proinflammatory cytokines and NKT cell apoptosis. In addition, NK cytotoxicity was found to be significantly lower in patients than in healthy controls, but NK cell levels were comparable in the 2 groups. Notably, this NKT cell deficiency was found to be correlated with NK cell dysfunction and to reflect active disease status. Furthermore, ␣GalCer-mediated NK cytotoxicity, showing the interaction between NK and NKT cells, was significantly lower in AOSD patients than in healthy controls.Conclusion. These findings demonstrate that NK and NKT cell functions are defective in AOSD patients and suggest that these abnormalities contribute to innate immune dysfunction in AOSD.

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Profound invariant natural killer T-cell deficiency in inflammatory arthritis

Abstract: iNKT cell deficiency is present in patients with RA and other inflammatory arthropathy. Normal iNKT cell frequency predicts non-inflammatory causes of joint pain.

Cited by 28 publications

References 36 publications

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

Invariant Natural Killer T Cells in Rheumatoid Arthritis and Other Inflammatory Arthritides

Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Natural killer T cell deficiency in active adult‐onset Still's disease: Correlation of deficiency of natural killer T cells with dysfunction of natural killer cells

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