Interstitial Lung Disease in Patients With Systemic Sclerosis: Toward Personalized-Medicine-Based Prediction and Drug Screening Models of Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD)

Abstract

Systemic sclerosis (SSc) is an autoimmune connective tissue disease, characterized by immune dysregulation and progressive fibrosis. Interstitial lung disease (ILD) is the most common cause of death among SSc patients and there are currently very limited approved disease-modifying treatment options for systemic sclerosis-related interstitial lung disease (SSc-ILD). The mechanisms underlying pulmonary fibrosis in SSc-ILD are not completely unraveled, and knowledge on fibrotic processes has been acquired mostly from studies in idiopathic pulmonary fibrosis (IPF). The incomplete knowledge of SSc-ILD pathogenesis partly explains the limited options for diseasemodifying therapy for SSc-ILD. Fibrosis in IPF appears to be related to aberrant repair following injury, but whether this also holds for SSc-ILD is less evident. Furthermore, immune dysregulation appears to contribute to pro-fibrotic responses in SSc-ILD, perhaps more than in IPF. In addition, SSc-ILD patient heterogeneity complicates the understanding of the underlying mechanisms of disease development, and more importantly, limits correct clinical diagnosis and treatment effectivity. Therefore, there is an unmet need for patient-relevant (in vitro) models to examine patient-specific disease pathogenesis, predict disease progression, screen appropriate treatment regimens and identify new targets for treatment. Technological advances in in vitro patient-relevant disease modeling, including (human induced pluripotent stem cell (hiPSC)-derived) lung epithelial cells, organoids and organ-on-chip technology offer a platform that has the potential to contribute to unravel the underlying mechanisms of SSc-ILD development. Combining these models with state-of-the-art analysis platforms, including (single cell) RNA sequencing and (imaging) mass cytometry, may help to delineate pathogenic mechanisms and define new treatment targets of SSc-ILD.

Flu and Pneumococcal Vaccine Coverage in Scleroderma Patients Still Need to Be Prompted: A Systematic Review

“…The mean age at the time of evaluation was 63.9, among patients vaccinated and 55. 4 among not vaccinated (p < 0.0001).…”

“…Systemic sclerosis (SSc), or scleroderma, is a rare autoimmune disease with a prevalence ranging worldwide from 10 to 40 cases per 100,000 individuals [3] characterized by excessive collagen production and deposition, often presenting symptoms overlapping with other rheumatological conditions. SSc pathogenesis is not yet completely unraveled [4]. However, most SSc-related deaths are determined by interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) caused mainly by a constant state of lung inflammation and cellular damage followed by fibroblast activation and subsequent fibrosis [5,6].…”

Interstitial lung disease in Indonesian adult with systemic sclerotic: A rare case

“…Should the patient is not tolerant to MMF, it is recommended to use 720 mg dose 3 ×/day [ 10 , 11 ]. In addition to MMF, cyclophosphamide (CYC) can be administered, in which the efficacy of administering CYC vs MMF in SSc-ILD is 42% vs 35% [ 11 , 12 ]. Previous studies showed that administration of CYC combined with prednisone can increase forced vital capacity (FVC) at 6 and 12 months of therapy [ 13 ].…”

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

“…A 3D organoid co-culture of synovial fibroblasts and endothelial cells has yielded results ( 58 ) of the NOTCH3 signaling cascade, that could be an important novel therapeutic target in RA. Another possibility is to use patient-derived cells ex vivo (i.e., in organoids) to predict individual patient drug responses ( 118 ). This was demonstrated by Kuo et al ( 59 ) who used dissociated synovial tissue-derived cells from RA patients, for testing currently used anti-inflammatory therapies.…”