Unmasking RA: no longer a case
of mistaken identity

New test helps pick out rheumatoid arthritis from the list of usual suspects

By Brian Hoyle

A slew of ailments is caused by the misguided attack of the body's immune system against parts of itself and foreign invaders. One of these autoimmune diseases is rheumatoid arthritis (RA). The disease is especially prevalent in middle-aged or older women, and significantly diminishes their quality of life.

Diagnosis of RA can be tricky. Many symptoms of RA are common to other diseases and as of yet there's no test that can reliably differentiate this condition from the rest. Currently, one clinical screen detects antibodies called rheumatoid factor (RF), yet this test is flawed because RF isn't present in all RA sufferers.

But all is not lost. Recently, Japanese researchers reported that the presence of certain antibodies may help distinguish RA from other autoimmune diseases. This latest research, reported in the January issue of the Journal of Rheumatology, focused on calpastatins � antibodies that block the action of calpains (calcium activated proteases). Calpains are involved in a wide variety of activities in the body, ranging from regulating biological systems to triggering apoptosis � the programmed destruction of cells. Too much or too little of these enzymes can spell trouble.

Given that calpains can destroy the cartilage that helps buffer the grinding of joints, one possible consequence of elevated levels may be RA, according to Dr Sachiko Iwaki-Egawa, assistant professor at the Hokkaido College of Pharmacy in Japan, and one of the study's authors.

The researchers reasoned that increased levels of calpains could be due to a decrease in its inhibitor � calpastatins. If so, then in an autoimmune disease like RA, antibodies to calpastatin might be produced.

Calpastatin generated by red blood cells was injected into patients suffering from RA and other autoimmune diseases. Serum from each patient was then screened for both anticalpastatin antibodies (IgG and IgM) using the enzyme-linked immunosorbent assay (ELISA).

The IgG antibody was found in the serum of almost 83% of the 58 participants with RA. When IgM was factored in, the percentage of those with RA soared to almost 90%. In contrast, the IgG antibody was found in only two of 11 patients (8.3%) of those with osteoarthritis, about 6% of those with systemic lupus erythematosus and only 20% of people with Sjögren's syndrome. The antibody wasn't even found in the serum of those with systemic sclerosis or mixed connective tissue disease.

Crunching all these numbers demonstrated that this antibody was almost completely specific to RA (96.1%). Further work is needed to see if the antibody level is consistent throughout the various stages of RA.