Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease

Abstract

Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of selftolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.

Proteomics analysis of lung tissue reveals protein makers for the lung injury of adjuvant arthritis rats

“…It can detect and clear pathogens, and also participates in certain other processes, such as the elimination of immune complexes ( 40 ), promoting angiogenesis ( 41 ), tissue regeneration ( 42 ), fibrosis and lipid metabolism ( 43 ). Abnormal activation of the complement system leads to homeostasis imbalance, contributing to a variety of autoimmune and inflammation-related diseases ( 44 ). Currently, the role of complement activation in the pathogenesis of lung injury secondary to RA is still unknown, but it may be useful for the development of effective therapies for RA secondary lung injury.…”

Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study

“…7 The activation of the complement system in RA appears to not only facilitate direct tissue damage but also contribute to the initiation of RA pathogenesis by interacting with citrullination protein. 8 C3 is the central molecule activated by the three complement pathways (classic, lectin, and alternative), which supports all important functions performed by it. 9 Hypocomplementemia (HC) is not uncommon in patients with autoimmune diseases.…”

“… 7 The activation of the complement system in RA appears to not only facilitate direct tissue damage but also contribute to the initiation of RA pathogenesis by interacting with citrullination protein. 8 …”

Do Ultrasound Lung Abnormalities Correlate to Biomarkers and Male Gender in Rheumatoid Arthritis Patients? A Monocentric Cross-Sectional Study

“…In the past decades, several RA features (sex, age, clinical and serological variables, and drug pathways) have been proposed as potential risk factors for ILD [ 34 ], and various circulating biomarkers have been linked to ILD survival [ 35 ]. However, an international consensus has not yet been reached, and their utility in early diagnosis of RA-ILD is still unclear.…”