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RA therefore can be divided into two subsets of disease entities (ACPA-positive RA and ACPA-negative RA), which are likely to be genetically distinct: HLA-DRB1 SE alleles and PTPN22 are restricted to ACPA-positive RA, while genes such as interferon regulatory factor 5 (IRF-5) and C-type lectin seem to confer risk for ACPA-negative RA [26]

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