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Arthritis

Rheumatoid Arthritis   |   Juvenile Arthritis   |   Publications

Rheumatoid Arthritis

Investigator: Ji Qiu, Ph.D.

Collaborators: Jerry Nepom, Ph.D. (Benaroya Research Institute), and Jane Buckner (Benaroya Research Institute)

Disease Background

Who gets it? What are the symptoms? Arthritis is a joint disorder that involves inflammation of one or more joints About 50 million adults in the USA have some form of arthritis Rheumatoid arthritis is most common in older women and family history increases risk of disease Some symptoms include serious pain, tightness and bumps on joints Arthritis is the most common cause of disability in the USA Joint damage makes it difficult to be physically active contributing to increased risk of obesity and depression

How do we detect it now? How is it currently treated? Arthritis is commonly detected by a doctor's exam, blood tests and X-rays Rheumatoid arthritis is difficult to diagnose because symptoms are similar to other diseases Treatment options include anti-inflammatory drugs, steroids, immunosuppressants and other drugs, therapy and surgery Most medications have serious side effects Joint erosions are irreversible and THERE IS NO CURE

What are the current challenges? The current molecular diagnostic tests available have a low sensitivity making it difficult to diagnose it early Delays in diagnosis result in delayed treatment and early treatment is essential in preventing irreversible joint damage

Our Approach

Anti-citrulline antibodies are specific and predictive of rheumatoid arthritis (RA). Seropositivity against citrulline is clinically assayed using cyclic citrullinated peptide (CCP) ELISA. Despite being an excellent proxy assay for diagnosis, anti-CCP positivity does not reveal any information about the actual underlying antigens that elicited the immune response. Recent studies demonstrated the value of identifying autoantibodies to particular antigens in the elucidation of RA etiology. Furthermore, the use of specific citrullinated antigens could improve diagnostic performance. Unfortunately, only a few citrullinated antigens have been discovered in the past several decades. Traditional protein immuno-chemistry methods to identify citrullinated antigens suffer drawbacks such as low throughput, poor reproducibility, inadequate quantification and low resolution. Commercial protein arrays are expensive, lack equal representation of candidate antigens and are not compatible with post-translational modifications such as citrullination, which requires harsh conditions. Our overarching goal is to discover additional antigens, when citrullinated, can be recognized by antibodies in RA patients at the proteome level. Identification of these citrullinated antigens will not only help understand the disease pathogenesis but also improve diagnosis and patient stratification.

 

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Juvenile Idiopathic Arthritis

Investigator: Ji Qiu, Ph.D.

Collaborators: David Gibson (Queens University)

Disease Background

Who gets it? What are the symptoms? Juvenile Arthritis describes autoimmune and inflammatory conditions that develop in children under the age of 16 Symptoms consist of swelling, pain, and stiffness Four major joints are affected: Shoulder, Elbow, Hip and Knee Some children will outgrow the symptoms, while others will need to continue with treatment on into adulthood Children who develop the disease after the age of 8, have a larger risk of developing an adult form of arthritis

How do we detect it now? How is it currently treated? Physical examination is conducted by a pediatric doctor   Medical history is recorded Lab work, x-rays, and other imaging tests No single blood test can confirm juvenile arthritis There is no cure for juvenile arthritis Treatment objective: Relieve inflammation and pain, while improving the child’s quality of life Treatment plans include: Medication, physical activity, and healthy eating Progress is carefully monitored Personalization - each child’s case is unique

What are the current challenges? Juvenile arthritis is a diverse disease, so the direct cause is not understood For instance, the source of pain can stem from other ailments Since this disease is autoimmune in nature, there are numerous auto-antibodies (antibodies that attack oneself) that have been observed Different forms of the disease exist and it is important to identify the correct form in each patient

Our Approach

Similar to Rheumatoid Arthritis, we expect to identify autoantibodies using NAPPA that provide diagnostic biomarkers for this disease.

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Publications

Gibson DS, Qiu J, Mendoza EA, Barker K, Rooney ME, LaBaer J. Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays. Arthritis Res Ther. Apr 17;14(2):R77. [Epub ahead of print] Abstract