NK Cell Patterns in Idiopathic Inflammatory Myopathies with Pulmonary Affection

Abstract

Background: Pulmonary affection (PA) is associated with a substantial increase in morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). However, the underlying immune mechanisms of PA remain enigmatic and prompt deeper immunological analyses. Importantly, the Janus-faced role of natural killer (NK) cells, capable of pro-inflammatory as well as regulatory effects, might be of interest for the pathophysiologic understanding of PA in IIM. Methods: To extend our understanding of immunological alterations in IIM patients with PA, we compared the signatures of NK cells in peripheral blood using multi-color flow cytometry in IIM patients with (n = 12, of which anti-synthetase syndrome = 8 and dermatomyositis = 4) or without PA (n = 12). Results: We did not observe any significant differences for B cells, CD4, and CD8 T cells, while total NK cell numbers in IIM patients with PA were reduced compared to non-PA patients. NK cell alterations were driven by a particular decrease of CD56dim NK cells, while CD56bright NK cells remained unchanged. Comparisons of the cell surface expression of a large panel of NK receptors revealed an increased mean fluorescence intensity of NKG2D+ on NK cells from patients with PA compared with non-PA patients, especially on the CD56dim subset. NKG2D+ and NKp46+ cell surface levels were associated with reduced vital capacity, serving as a surrogate marker for clinical severity of PA. Conclusion: Our data illustrate that PA in IIM is associated with alterations of the NK cell repertoire, suggesting a relevant contribution of NK cells in certain IIMs, which might pave the way for NK cell-targeted therapeutic approaches.

High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies

“…A subgroup of patients in all three groups did not receive any immunotherapy at time of blood sampling, while the remaining patients received immunosuppressive therapies ( Table 1 ). We selected these cohorts as they reflect clinical and epidemiological characteristics previously described for the IIM spectrum [ 3 , 13 , 14 ].…”

“…The burden of disease is amplified by extra-muscular affection commonly present in IIM [ 3 ]. Consequently, IIM has evolved into a systemic inflammatory disease spectrum involving multiple organs.…”

“…Among these, IBM is unique due to its characteristic clinical presentation, treatment refractory disease course and controversial viewpoints regarding its pathogenesis [ 4 ]. Exemplifying IIM with predominance of extra-muscular features, anti-synthetase syndrome (ASyS) is distinguished by myositis, interstitial lung disease, mechanic’s hand and arthritis [ 3 , 5 ]. While our understanding of immunological hallmarks of certain IIM has evolved over the past decade, the immune signatures driving chronicity of IIM remain largely enigmatic.…”

Five genes as diagnostic biomarkers of dermatomyositis and their correlation with immune cell infiltration

“…But in DM muscle, the resting NK cells significantly decreased and the activated NK cells significantly increased. In previous studies, the levels of periphery NK cells in DM patients were decreased, which may be related to NK cells migration into muscle ( 54 , 55 ). Therefore, we speculated that the up-regulation of activating NK cells infiltration in DM muscle was related to the migration of peripheral cells and the activation of resting NK cells in muscle.…”

Prognostic significance of natural killer cell depletion in predicting progressive fibrosing interstitial lung disease in idiopathic inflammatory myopathies

“…Previous studies have found numerical or functional dysregulation of circulating natural killer (NK) cell plays a pivotal role in IIM-ILD ( 25 , 26 ). One of our recent studies discovered that an amyopathic dermatomyositis-associated ILD group with a cluster of activated CD45RA + HLA-DR + CD8 + T cells and a reduced proportion of CD56 dim NK cells showed a high prevalence of rapidly progressive ILD and increased mortality rates ( 27 ), indicating that peripheral lymphocyte immunological profiles have predictable potential for the development of ILD fibrotic progression.…”