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Plasma biomarker for detection of onset of chronic Rheumatoid Arthritis

Background:
Rheumatoid Arthritis is characterized by inflammation of joints resulting in joint damage and disability. Research demonstrated that the presence of Rheumatoid Arthritis specific auto-antibodies directed against citrullinated proteins (ACPA) in the serum of patients increased the risk of developing the disease in patients with pain in their joints. ACPA can already be detected in patients years before onset of disease.

Technology Overview:
Researchers at the LUMC have recently discovered that ACPA isolated from Rheumatoid Arthritis patients is decorated with unique sugar structures. These sugar structures are not, or to a lesser extent, present on ACPA of people not yet diagnosed with Rheumatoid Arthritis. This unique sugar structure attached to ACPA could represent a biomarker of the transition phase from healthy to disease. Currently, researchers at the LUMC are investigating the possibility of a diagnostic test to analyse the sugar structures attached to ACPA on a large scale. Based on this test, the sugar structures of ACPA can predict the development of Rheumatoid Arthritis in patients with joint pain. This knowledge is important for clinicians to select an appropriate treatment in time to prevent progression towards chronic Rheumatoid Arthritis.

[Figure 1: ACPA with unique sugar structures are specifically present in patients with Rheumatoid Arthritis and might be crucial to predict progression from auto-antibody positive healthy subjects to patients with full-blown, chronic and persistent arthritis.]

Benefits:
ACPA appear in the blood of Rheumatoid Arthritis patients up to ten years before onset of disease. Currently it is impossible to predict the exact time point of disease manifestation. Therefore, treatment starts at diagnosis of the disease. At this stage, the disease is already chronic, and the patient is devoted to lifelong treatment. This invention allows clinicians to intersect the healthy auto-reactive positive pre-disease phase from the pathogenic phase in which Rheumatoid Arthritis development commenced. If in this stage therapy is applied, development towards Rheumatoid Arthritis might be stopped before chronification occurs.

Further Details:
More background information can be found in the publication: “Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis.”, Rombouts et al., Ann Rheum Dis. 2016 Mar.

Potential Applications:
Identify ACPA+ individuals with high risk to develop Rheumatoid ArthritisTargeted treatment - distinguish individuals with high risk to develop Rheumatoid Arthritis in the “at risk” group and start treatmentEarlier start of treatment to prevent/delay/decrease severity and chronification of Rheumatoid Arthritis

Opportunity:
The researchers are looking for partner(s) to license and further (co-)develop and market this assay for clinical application. Specifically companies that are developing diagnostic tools for inflammatory diseases.

IP Status:
Priority patent filed

 

Luris reference number

INV-0407.0314

Further information

Vincent van der Mark Knowledge Broker (LUMC Div. 2/3) +31-71-527 2652 +31-6-1474 7912 v.a.van.der.mark@luris.nl