Send to

Choose Destination
Arthritis Rheumatol. 2019 Aug 12. doi: 10.1002/art.41075. [Epub ahead of print]

Pro-inflammatory histidyl-tRNA synthetase-specific CD4+ T cells in the blood and lung of patients with idiopathic inflammatory myopathies.

Author information

Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, 17176, Stockholm, Sweden.
Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Solna, SE-17176, Stockholm, Sweden.
Department of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.



Autoantibodies targeting histidyl-tRNA synthetase (HisRS, or anti-Jo1) are common in idiopathic inflammatory myopathies (IIM) and anti-synthetase syndrome (ASS). We aimed to investigate immunity against HisRS in blood and lungs of patients with IIM/ASS.


Bronchoalveolar lavage fluid (BALF), BALF cells and peripheral blood mononuclear cells (PBMCs) from IIM/ASS (n=24) patients were stimulated with full-length HisRS-protein or a HisRS-derived peptide (HisRS11-23 ). BALF and PBMCs from sarcoidosis patients (n=7) and healthy controls (HCs, n=12) were included as controls. CD4+ T-cell response was assessed by CD40L upregulation and cytokine expression using flow cytometry. Anti-Jo1 autoantibody response in serum and BALF was assessed by ELISA. Lung biopsies (n=14) were investigated by immunohistochemistry.


In BALF, CD4+ T cells from 3/4 IIM/ASS responded to HisRS-protein stimulation (median CD40L fold-change: 3.6; 2.7-14.7) and 2/3 IIM/ASS had the highest responses to HisRS11-23 (median CD40L fold-change: 88; 27-149). In PBMCs, CD4+ T cells from 14/18 IIM/ASS responded to HisRS-protein (median fold-change: 7.38; IQR, 2.69-31.86, p<0.001) whereas HisRS11-23 response was present in 11/14 IIM/ASS (median fold-change: 3.4, IQR 1.87-10.9, p<0.001). In the control group, there was a HisRS11-23 response in 3/7 sarcoidosis (median CD40L fold-change: 2.09; IQR, 1.45-3.29), and in 5/12 HCs (median fold-change: 2; IQR, 1.89-2.42). CD4+ T cells from IIM/ASS displayed a pronounced Th1 phenotype in BALF when compared to PBMCs (p<0.001), producing high amounts of IFNγ and IL-2 following stimulation. Anti-Jo1 autoantibodies were detected in BALF as well as germinal center (GC)-like structures in lung biopsies of IIM/ASS.


We report the pronounced presence of HisRS-reactive CD4+ T cells in PBMCs and BALF cells of IIM/ASS patients compared to sarcoidosis patients and HCs. This combined with the presence of anti-Jo1 autoantibodies in BALF, and GC-like structures in the lungs suggest that immune activation against HisRS might take place within the lungs of IIM/ASS patients. This article is protected by copyright. All rights reserved.


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center