Seronegative Rheumatoid Arthritis

Seronegative rheumatoid arthritis (also called sero negative rheumatoid arthritis) refers to a patient with RA who has a level of Rheumatoid factor below the laboratory’s test criteria.

As background, rheumatoid factor is an antibody that binds to other antibodies in the same patient. Traditionally, rheumatoid factor was an immunoglobulin M (IgM) that bound to the patient’s own IgG antibodies in the constant region of the gamma chain (Fc portion). Now, clinicians also test the patient’s sera to see if rheumatoid factor is an IgA or IgG type antibody.

The presence of rheumatoid factor is one of 7 criteria used in the diagnosis of rheumatoid arthritis. Other names for rheumatoid factor include rheumatoid arthritis factor or RF.

Scientists or clinicians often measure RF by the ELISA method or the laser nephelometry assay (1). Values less than 45 IU/ml are often considered negative, although each laboratory may have its own cutoff value. Scientists measuring RF by Latex fixation method often interpret a titer below 1:80 as negative (1).

In other words, the seronegative rheumatoid arthritis patient has very low or undetectable levels of rheumatoid factor.

Potential initiating cause in some seronegative RA patients

Seronegative RA patients were more likely to have a bone fracture or other physical trauma within 6 months of RA diagnosis than seropositive patients (2).

Physical trauma such as a bone fracture occurred within 6 months of diagnosis of rheumatoid arthritis in approximately 21% of rheumatoid patients in a clinical survey (2).

Does a seronegative rheumatoid arthritis patient always remain negative?

Approximately half of RA patients are seronegative during the first six months of illness (1).

However, after 2 years of illness, only 15% of RA patients remain seronegative for RF factor (1).

Do seronegative patients have antibodies that react with other proteins in the damaged joints?

Yes, some seronegative rheumatoid arthritis patients do. For example, in a study of 23 seronegative patients, 11 had anti-CCP antibodies and 6 had anti-keratin antibodies (3)

The patients with anti-CCP antibodies had a higher risk for erosions and deformities (3) and poorer functional status (4).

Can other arthritis diseases be diagnosed as seronegative rheumatoid arthritis?

Diagnosis of rheumatoid arthritis is based on 7 criteria, only one of them being a titer of RF. About 1 of every 7 Rheumatoid arthritis patients do not contain detectable RF and are thus named seronegative.

The 100 types of arthritis have overlapping symptoms. Common types of arthritis that are also seronegative for rheumatoid factor include:

Ankylosing spondylitis, bacteria endocarditis, calcium pyrophosphate deposition disease, gout, polymyalgia rheumatic, osteoarthritis, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, septic arthritis, systemic lupus erythematosus, undifferentiated spondyloarthropathy, and viral arthritis.

Other types of seronegative arthritis that are less commonly diagnosed include Dermatomyositis, enteropathic arthritis, juvenile onset or adult onset idiopathic arthritis, Polymyositis, Sjogren’s syndrome, Scleroderma, sarcoidosis, Systemic Vasculitis, Whipple’s Disease, and various types of arthritis caused by bacteria (Lyme arthritis, Gonococcal arthritis, Rheumatic fever, tuberculous arthritis).


In summary, seronegative rheumatoid arthritis means that this RA patient does not have significant levels of rheumatoid factor. Because the patient does not contain RF factor, the seronegative RA patient may have a less aggressive disease course. However, many of the RA patients who were initially seronegative for RF may later develop significant titers (levels) of RF factor.


Some seronegative rheumatoid arthritis patients have a bone fracture within 6 months of beginning the RA symptoms.

It may be beneficial if these RA patients eat a diet rich in all the nutrients needed for bone and joint repair so they heal the bone fracture and joint as rapidly as possible.

Could healing the bone fracture as rapidly as possible help resolve the symptoms?

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