Interstitial Lung Disease Associated with Anti-Ku Antibodies: A Case Series of 19 Patients

Abstract

Background: Antibodies against Ku have been described in patients with various connective tissue diseases. The objective of this study was to describe the clinical, functional, and imaging characteristics of interstitial lung disease in patients with anti-Ku antibodies. Methods: This single-center, retrospective observational study was conducted at a tertiary referral institution. Patients with positive anti-Ku antibodies and interstitial lung disease identified between 2007 and 2022 were included. Clinical, immunological, functional, and imaging data were systematically reviewed. Results: Nineteen patients (ten females) with a mean age of 59 ± 12.6 years were included. The most frequent associated diagnosis was systemic sclerosis (42%), followed by rheumatoid arthritis (26%), Sjögren syndrome, undifferentiated connective tissue disease, and overlap between systemic sclerosis and idiopathic inflammatory myopathy (scleromyositis). Imaging revealed frequent septal and intralobular reticulations and ground-glass opacities, with nonspecific interstitial pneumonia as the predominant pattern (53%). The mean forced vital capacity was 82% ± 26 of the predicted value, and the mean diffusing capacity for carbon monoxide was 55% ± 21. Over the first year of follow-up, the mean annual forced vital capacity decline was 140 mL/year (range: 0-1610 mL/year). The overall survival rate was 82% at 5 years and 67% at 10 years. Conclusions: Most patients with interstitial lung disease and anti-Ku antibodies presented with dyspnea, a mild-to-moderate restrictive ventilatory pattern, and reduced diffusing capacity for carbon monoxide. The CT pattern was heterogeneous but was consistent with nonspecific interstitial pneumonia in half of the patients.

Keywords: autoimmunity; connective tissue disease; pulmonary fibrosis.

Figure 1

Flowchart of the study. CT: computed tomographyl; ILD: interstitial lung disease.

Figure 2

Characteristic speckled nuclear fluorescence pattern of anti-Ku antibodies observed on HEp-2 cells by indirect immunofluorescence. The white arrow highlights the nucleus of a cell in metaphase with fluorescence around the chromatin and negative mitoses.

Figure 3

Computed tomography of a male patient with anti-Ku antibodies, demonstrating a pattern of fibrotic nonspecific interstitial pneumonia. (A) Axial view of lower part of the lungs, demonstrating diffuse distribution of ground-glass opacities, reticulation, bronchiectasis, and bronchiolectasis. (B) Sagittal view showing apicobasal distribution. (C) Coronal view, with minimal intensity projection of 13 mm. (D) Sagittal view, with minimal intensity projection of 13 mm.

Figure 4

Computed tomography of a male patient with anti-Ku antibodies, demonstrating a pattern of fibrotic nonspecific interstitial pneumonia, apicobasal distribution of ground-glass opacities and reticulation with subpleural sparing, bronchiectasis, and bronchiolectasis, associated with paraseptal emphysema. (A) Upper part of the lungs, axial view. (B) Middle part of the lungs, axial view. (C) Lower part of the lungs, axial view. (D) Sagittal view, with a minimal intensity projection of 5 mm.

Figure 5

Kaplan–Meier estimates of overall survival. The solid line represents the estimate of overall survival. The dotted lines represent the 95% confidence interval.