Study of the Week: Targeting of Laminin-521 in Anti-GBM Disease Linked to Lung Damage

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Laminin-521 is a novel target of autoantibodies associated with lung hemorrhage in anti-GBM disease

We previously published about this research in a story titled “What is Laminin-521’s Role in Anti-Glomerular Basement Membrane Disease?” which can be found here. The study was originally published in the Journal of the American Society of Nephrology. You can view the abstract of the study here.

What Happened?

Anti-glomerular basement membrane disease (anti-GBM disease) is an illness with a known autoimmune mechanism. Autoantibodies attack an area called the basement membrane in the lungs and kidneys. These autoantibodies are able to recognize epitopes of the α345(IV) collagen, which is a major component of the basement membranes in these organs. Another well known component of the glomerular basement membrane (GBM) is laminin-521.

Laminin-521 is a known antibody target in animal models of glomerulonephritis, a key symptom in anti-GBM disease. The goal of this study was to determine if the autoantibodies in this illness targeted laminin-521 as well. This was a retrospective study that evaluated the circulating autoantibodies in 101 patients whose data was compared alongside a control group of 85 volunteers. A solid-phase immunoassay was utilized in order to evaluate IgG binding to laminin-521.

The evaluation found autoantibodies that bound to laminin-521 in around a third of the anti-GBM patients in the study. None of these antibodies were identified in the healthy controls. Patients whose symptoms included lung involvement, such as lung hemorrhage, were much more likely to have these autoantibodies (51.5 percent of cases vs 23.5 percent in those without) . These autoantibodies were of the IgG1 and IgG4 subclasses and were linked to smoking and hemoptysis, along with the aforementioned lung hemorrhage. 

About Anti-glomerular Basement Membrane Disease (Anti GBM Disease)

Anti-GBM disease is a rare autoimmune illness characterized by bleeding in the lungs and rapidly progressing glomerulonephritis, which often leads to kidney failure. The disease is also called Goodpasture syndrome. Like with many other autoimmune diseases, a precise cause is unknown, but there is a genetic predisposition linked to HLA-DR15. Some degree of disturbance or damage to the lungs appears to trigger symptom onset; examples include smoking, cocaine inhalation, sepsis, and lung infections. Aside from glomerulonephritis, other symptoms can include hematuria, proteinuria, swelling, uremia, high blood pressure, shortness of breath, coughing up blood, chest pain, joint pain, fever, weight loss, fatigue, and chills. Primary treatments include plasmapheresis and immunosuppressants, such as rituximab, cyclophosphamide, and prednisone. If treated effectively, five year survival rate is better than 80 percent, but some patients may require dialysis. The disease is fatal without treatment. To learn more about anti-GBM disease, click here.

Why Does it Matter?

The findings confirm that autoantibodies in anti-GBM disease can and do target laminin-521, as animal models of glomerulonephritis had suggested. In addition, the researchers discovered that this targeting plays a critical role in the lung symptoms that are seen in many patients living with the disease. The researchers believe that this occurs because it increases the number of autoantibodies that bind to the alveolar basement membranes.

These revelations give the medical community a more thorough understanding of the mechanism involved in anti-GBM disease that could allow for more effective treatment of patients in the future. In patients that are not treated in time, lung hemorrhages can be the ultimate cause of death. Therefore, patients that present with lung involvement are at greater risk then those that only have kidney-related symptoms.

This understanding of the disease mechanism could lead to the development of more precisely targeted medicines that can treat the illness with a reduced risk of adverse effects that are associated with many widely used immune-suppressing therapies.

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