Genetic studies confirm two distinct sub-types of rheumatoid arthritis

A new study published in the American College of Rheumatology journal by researchers in Manchester has found that anti-CCP (anti-cyclic citrullinated peptide antibody) negative and positive rheumatoid arthritis are two genetically different disease subclasses that only partially share vulnerability factors.

Anti-CCP is a blood test which helps doctors confirm a diagnosis of rheumatoid arthritis. Genetic polymorphisms within the human leukocyte antigen (HLA) region explain only a modest proportion of anti-CCP negative rheumatoid arthritis heritability. However, few non-HLA markers have been identified so far.

Dr Sebastien Viatte from the Arthritis Research UK Centre for Genetics and Genomics at The University of Manchester undertook research, to replicate non-HLA markers from a previous study.

Using data from the Rheumatoid Arthritis Consortium International (RACI) researchers worked to determine differences in the genetic make-up of 186 autoimmune-related regions in 3,297 anti-CCP negative rheumatoid arthritis patients and more than 15,000 controls across six different populations using the Illumina ImmunoChip array.

The study found that non-HLA genetic markers of anti-CCP negative do exist and their effect size is smaller than susceptibility markers for anti-CCP positive rheumatoid arthritis (meaning that larger sample sizes are required for detection). It was also found that they might not be preferentially located in autoimmune-related genetic regions previously associated with other complex autoimmune diseases and that anti-CCP negative rheumatoid arthritis is likely to comprise several genetically distinct disease entities.

Professor Jane Worthington from the NIHR Manchester Musculoskeletal Biomedical Research Unit (BRU) said:

Further studies are needed to confirm the associations reported in our research; our results support the evidence that that anti-CCP negative and positive rheumatoid arthritis represent two genetically distinct disease subsets.

“These two diseases will need to be independently investigated in further studies by increasing sample size and developing new approaches until innovative methods of genetic and environmental diagnostics can enter clinical practice.”