Clinical features and immune-related protein patterns of anti-MDA5 positive clinically amyopathic dermatomyositis Dutch patients

Abstract

Objectives The presence of melanoma differentiation-associated protein 5 (MDA5) antibodies in patients with dermatomyositis (DM) is associated with the development of a rapidly progressive interstitial lung disease (RPILD), unresponsive to conventional treatment. We characterize patients and provide more insight into potential biomarkers to identify patients with RPILD. Methods Patients diagnosed with anti-MDA5 positive DM between December 2015 and November 2017 were included in this study. Clinical data were retrospectively retrieved from medical records. 180 immune-related markers were measured in sera of 16 patients and 15 healthy controls using proximity extension assay based technology. Results Twenty patients were included, with a median time from symptoms till diagnosis of 4 months. All patients had clinically amyopathic DM. Interstitial lung disease (ILD) was present at diagnosis in 94% of the patients, 45% presented with RPILD. The mortality rate was 35% within 4 months after diagnosis and respiratory failure was the main cause of death in these patients. Furthermore, unsupervised analysis revealed that patients with RPILD show clearly different inflammatory serum profiles than healthy controls. In addition, in comparison to healthy controls, the interferon, Interleukin (IL)1, IL10 and IL18 signalling pathways are different regulated in anti-MDA5 positive patients. Conclusion In this Dutch anti-MDA5 positive CADM cohort, one third of the patients died due to RPILD soon after diagnosis, which underlines the severity of this disease. In addition, we have found several possible pathways that are differentially regulated in RPILD vs no RPILD DM and healthy controls. These markers await further validation before clinical use.

Rare complications of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: Time to nip them in the bud

“…Several studies found that a majority of MDA5 + DM or CADM patients presented elevated levels of serum cytokines, including IFN-a, IFN-b, IFN-g, IL-1b, IL-6, IL-10, IL-18 and IL-12 (62-64). Hensgens et al (65) found that signaling pathways of IFN, IL-1, IL-10 and IL-18 families upregulated in MDA5 + DM in comparison to healthy individuals. Increased C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 could be also observed in CADM patients (64).…”

“…Hensgens et al. ( 65 ) found that signaling pathways of IFN, IL-1, IL-10 and IL-18 families upregulated in MDA5 + DM in comparison to healthy individuals. Increased C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 could be also observed in CADM patients ( 64 ).…”

Anti-MDA5 dermatomyositis: an update from bench to bedside

“…In a recent single-centre retrospective Chinese cohort [35], three clusters emerged of which two were comparable to the French study: one mainly showing arthritis and mechanic's hands with low rates of RP-ILD and a good prognosis; one enriched in RP-ILD which was also exhibiting fever, hyperferritinemia and a far worse prognosis. In contrast, a different third cluster identified patients with high rates of typical cutaneous signs and enriched in clinically relevant myositis, with very low rates of RP-ILD (Table 1) [65].…”

Multivariate logistic regression analysis of poor prognosis of dermatomyositis and clinical value of ferritin/Kl‐6 in predicting prognosis

“…One of the most common lung lesions in DM/PM patients is interstitial lung disease (ILD). Patients with this complication have high morbidity and mortality rates, ranging from 20% to 78% 12 . Salivary sugar chain antigen‐6 (KL‐6), as an indicator that can reflect lung injury, has been paid more and more attention by researchers 13 .…”

“…Patients with this complication have high morbidity and mortality rates, ranging from 20% to 78%. 12 Salivary sugar chain antigen‐6 (KL‐6), as an indicator that can reflect lung injury, has been paid more and more attention by researchers. 13 Importantly, DM patients with anti‐MDA5 antibodies face a significant risk of ILD and exhibit a quickly worsening disease trajectory, making early detection of this condition critical.…”