Polymorphism and antibodies associated with highly increased risk of rheumatoid arthritis

December 21, 2005

People who have a specific genetic variant of the PTPN22 gene and test positive for antibodies against cyclic citrullinated peptide are much more at risk of developing rheumatoid arthritis than people who only have one of these markers. A study published today in the journal Arthritis Research & Therapy reveals that a group of people who have a specific genetic variant, or polymorphism, of PTPN22, a gene that encodes a tyrosine phosphatase protein, and tested positive for anti-cyclic citrullinated peptide (CCP) antibodies, all developed rheumatoid arthritis (RA) in the following two and a half years. Both the polymorphism and anti-CCP antibodies have previously been shown to be associated with RA, but in combination they give a much higher risk of developing the disease than separately. This combination gives a much higher relative risk than the combination of anti-CCP antibodies and the previously well-known genetic factor, namely HLA DR4 antigens.

Martin Johansson and colleagues from the University Hospital in Umea, Sweden studied a population of 92 patients diagnosed with RA for whom a blood sample was available, which had been taken on average about two and a half years before the onset of the disease. They were matched with controls - blood donors from the same group who didn't develop arthritis - for age, sex, and rural or urban residence.

The presence of the PTPN22 1858T polymorphism was determined by genotyping and anti-CCP antibodies were detected by immunoassay of the blood samples taken two and a half years before onset of the disease.

Johansson et al.'s results confirm previous findings that RA patients are more likely to have the PTPN22 1858T polymorphism than controls. Individuals with the PTPN22 1858T polymorphism were more likely to be positive for anti-CCP antibodies, but none of the controls with the polymorphism were positive for anti-CCP antibodies. All of the blood donors who had anti-CCP antibodies and have the PTPN22 1858T polymorphism had developed RA an average of two and a half years after the blood sample was taken.
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Article:
PTPN22 polymorphism and anti-CCP antibodies in combination strongly predicts future onset of rheumatoid arthritis and has a specificity of 100% for the disease.
Martin Johansson, MSc, Lisbeth Ärlestig, MSc, Göran Hallmans MD, PhD and Solbritt Rantapää-Dahlqvist, MD, PhD
Arthritis Research & Therapy 2006, 8:R19 (22 December 2005)

BioMed Central

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