Profound invariant natural killer T-cell deficiency in inflammatory arthritis.
OBJECTIVE
Data from rodent models indicate that invariant natural killer T (iNKT) cells are key regulators of many immune responses including autoimmune arthritis, but their role in human diseases is unclear. The aims of this study are to determine whether iNKT cell frequency and function are altered in patients with rheumatoid arthritis (RA), and the clinical significance of such iNKT cell abnormalities.


METHODS
Peripheral blood iNKT cell frequency and proliferative response to an iNKT cell-specific agonist, α-galactosylceramide were measured in 46 RA patients (including 23 untreated, newly diagnosed patients), 22 healthy controls and 27 patients presenting with recent-onset joint pain. The relationship between iNKT cell frequency and clinical characteristics and the effects of immunosuppressive treatment was examined.


RESULTS
Compared with healthy controls, RA patients had a decreased frequency of peripheral blood iNKT cells (median 0.001% vs 0.021%, p<0.001) and the proliferative response of this subset to α-galactosylceramide was also diminished in the patient group (median fold-expansion 31 vs 121, p=0.037). These abnormalities preceded the initiation of disease-modifying or immunosuppressive therapy, whose effect was to increase the circulating iNKT cell frequency (p=0.037). Furthermore, iNKT cell frequency correlated inversely with the systemic inflammatory marker, C-reactive protein (p=0.008). Finally, in patients presenting with recent-onset joint symptoms, normal peripheral blood iNKT cell frequency predicted a non-inflammatory cause of joint pain.


CONCLUSIONS
iNKT cell deficiency is present in patients with RA and other inflammatory arthropathy. Normal iNKT cell frequency predicts non-inflammatory causes of joint pain.
Tudhope
Susan J
SJ
Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK.
von Delwig
Alexei
A
Falconer
Jane
J
Pratt
Arthur
A
Woolridge
Tom
T
Wilson
Gillian
G
Isaacs
John D
JD
Ng
Wan-Fai
WF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D018771:Arthralgia / Q000175:diagnosis; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D002097:C-Reactive Protein / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D010003:Osteoarthritis / Q000175:diagnosis; D055815:Young Adult
D018501:Antirheumatic Agents; D005699:Galactosylceramides; D007166:Immunosuppressive Agents; C493154:alpha-galactosylceramide; D002097:C-Reactive Protein; D008727:Methotrexate