In rheumatoid arthritis, a genetic abnormality is associated with a progressively shortening lung disease, idiopathic pulmonary fibrosis. It allows for the first time to hope for an early diagnosis, as well as a specific treatment.
Lung involvement, whether or not it causes shortness of breath, is a common extra-articular involvement of rheumatoid arthritis (RA). The high-resolution scanner reveals, in fact, pulmonary abnormalities in more than half of patients suffering from RA. Disabling interstitial lung disease will develop in approximately 10% of patients.
Unfortunately, it is currently difficult to identify in which patients the attack of the lungs will be complicated and therefore it is still impossible to intervene early in the evolutionary course of the lung disease.
A genetic study could well change this because it shows that an anomaly of the gene coding for an important mucus protein is more frequent in these patients at risk of lung disease. This study had the honors of various congresses and of a publication in the New England Journal of Medicine.
chronic lung disease
Idiopathic pulmonary fibrosis is the most common non-infectious lung disease affecting the interstitial tissue: “idiopathic diffuse interstitial lung disease”. In the general population, it can occur around the age of 65 with shortness of breath on exertion, which gradually sets in.
The mechanism of onset of idiopathic pulmonary fibrosis involves several issues, including abnormal secretion of surfactant (the fluid that keeps the air cells open), a predisposition to cell aging (shortening of telomeres), and disruption of cell cleaning. bronchi by mucus and cilia on the surface of the bronchial cells, the latter moving the mucus up the throat like a treadmill (ciliary clearance).
Mucins are proteins that are an important component of the mucus that lines the bronchial tubes in the lung. This mucus is a defensive barrier, as well as a mechanism for eliminating inhaled particles and pathogens. As shown in one study, the MUC5B protein is very common in the cells lining the bronchi within lesions typical of pulmonary fibrosis in an autoimmune disease such as rheumatoid arthritis and it is likely that its overexpression is genetically controlled. and that these abnormalities can disrupt this famous process of cleaning the lungs or ciliary clearance.
An anomaly very often associated
Clinical heterogeneity characterizes many autoimmune diseases. Studies in search of genetic abnormalities involved in these autoimmune and inflammatory diseases have yielded hundreds of genetic associations. However, most of these associations have only an extremely modest effect and their practical implications have been slow to emerge. In RA, the effect of HLA abnormalities outweighs the other 100 identified genetic abnormalities, but their effect on lung disease is modest.
The study by Pierre-Antoine Juge, first author of this publication, constitutes an interesting exception to this rule of weak genetic influence on diseases. The abnormality of the gene coding for the MUC5B protein (rs35705950) represents approximately 30 to 35% of the genetic risk of development of idiopathic pulmonary fibrosis in the general population. Surprisingly, in rheumatoid arthritis, those who carried this anomaly have a risk multiplied by 3 of diffuse interstitial lung disease (Odds ratio of 3.1 with a confidence interval at 95%, 1.8 to 5.4), even when the researchers take into account smoking which is a major risk factor, age and gender.
A new therapeutic avenue
In patients with rheumatoid arthritis, this strong association of the abnormality of the gene encoding the MUC5B protein with idiopathic pulmonary fibrosis raises the question of whether all patients with RA should not be tested for abnormality status. of MUC5B. This is ideal if early detection allows preventive treatments.
Additionally, once lung disease is authenticated, MUC5B genotyping may provide information about prognosis and, as understanding of pathogenesis improves, could guide treatment. This study supports the concept that genetics can now really contribute to a better understanding of autoimmune diseases and new insights into the future.
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