ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1263

Evidence for the Involvement of NK Cells in Antisynthetase Syndrome

Baptiste Hervier1, Yves Allenbach2, Mikael Perez3, Hervé Devilliers4, Fleur Cohen-Aubart5, Zahir Amoura6, Werner Stenzel7, Isabelle Cremer8, Olivier Benveniste2 and Vincent Vieillard1, 1INSERM UMR-S 1135, UPMC, Paris, France, 2UMR 974, Sorbonne Universités, University Pierre et Marie-Curie-Paris 6, INSERM, Paris, France, 3UMR-S 1138, INSERM & UPMC, Paris, France, 4CHU de Dijon, Dijon, France, 5Internal Medicine Dpt 2, Pitié-Salpêtrière Hospital, APHP, Paris, France, 6Internal medicine 2, French National Reference Center for Systemic Lupus and Antiphospholipid Syndrome, Pitié-Salpêtrière Hospital (AP-HP), Paris, France, 7Department of Neuropathology, Charite Hospital, Berlin, Germany, 8INSERM UMR-S 1138, INSERM & UPMC, Paris, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Muscle Biology, Myositis and Myopathies: Myositis Autoantibodies and Disease Phenotype

Session Type: Abstract Submissions (ACR)

Background/Purpose Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti-tRNA-synthetase autoantibodies. Its pathogenesis remains unknown, especially regarding the involvement of innate immune cells, including natural killer (NK) cells. Here, we describe the first phenotypic and functional characterization of NK cells in this context.

Methods A total of 20 patients with inactive and active aSS were included (women/men =9, median age =50 years), and compared to 20 healthy controls. Freshly isolated NK cell phenotype was performed by Flow cytometry. Polyfunctionality assays were performed to measure degranulation and intracellular production of TNFa and IFNg, spontaneously or after stimulation by interleukin(IL)-12 and IL18, in the presence of K562 target cells. The presence and the localization of NK cells in primary human specimens of lung (n=3) and muscle (n=3) target tissue were studied by immunohistochemistry, using anti-NKp46 monoclonal antibody.

Results NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by a increased level of CD57 (p=0.09) and ILT2 (p=0.016) associated with decreased CD161 (p=0.052) and NKp30 (p=0.009), compared to healthy donors. This is consistent with the inability of circulating NK cells of active aSS patients to produce IFNγ (p=0.0017) after IL12 plus IL18 stimulation, compared to healthy controls. More importantly, our in-depth analysis reveals that NKp30 down-modulation strongly correlated with the loss of NK cell functions (Spearman coefficient r=0.57, p=0.009), and could be a surrogate marker of aSS activity. Histological studies reveal for the first time the presence of small numbers of  NK cells in the muscles, as well as a massive infiltration of NK cells inside the lungs of aSS patients.

Conclusion Taken as a whole, NK cell phenotypic and polyfunctional changes as well as infiltration of target tissue argue for an involvement of NK cells in aSS pathogenesis.

Disclosure:

B. Hervier,
None;

Y. Allenbach,
None;

M. Perez,
None;

H. Devilliers,
None;

F. Cohen-Aubart,
None;

Z. Amoura,
None;

W. Stenzel,
None;

I. Cremer,
None;

O. Benveniste,
None;

V. Vieillard,
None.

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