Background Smoking has been linked to production of anti-citrullinated protein antibodies (ACPA) in HLA-DRB1 shared epitope positive patients which has also been associated with a worse severity of rheumatoid arthritis (RA) [1, 2]. In addition, a single amino acid change R620W (rs2476601) in the protein tyrosine phosphatase non-receptor 22 (PTPN22) has been found to interact with smoking and ACPA positivity .
Despite this, a recent study  (N=532) found no evidence that smoking increased the risk of being ACPA positive. In addition, they reported a protective effect of smoking on the development of bone erosions in subjects who had ever smoked (OR=0.44, 95%CI 0.3-0.7, P≤0.0001) and a larger protective effect when subjects ever smoked in combination with carrying at least one of the PTPN22 single amino acid changes R620W (rs2476601) (OR=0.25, 95%CI 0.1-0.6, P=0.002) .
Objectives To investigate the inter-relationships between smoking, protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W genotype and anti-citrullinated peptide antibodies (ACPA) status and to investigate the inter-relationships between smoking, PTPN22 R620W genotype and presence of bone erosions in patients with RA.
Methods Six studies totalling 2680 RA patients were included in a Mantel-Haenszel fixed effects meta-analysis investigating ACPA status and eight studies totalling 3172 RA patients were included in a Mantel-Haenszel fixed effects meta-analysis investigating presence of erosive damage.
Results Evidence was found for an increase in the odds of ACPA positivity for ever smoking (OR=1.56, 95%CI 1.28-1.90, p=8.5 ×10-6), carriage of at least one of the PTPN22 risk alleles (OR=1.50, 95%CI 1.13-2.00, P=0.0055) and both ever smoking and carriage of at least one of the PTPN22 risk alleles (OR=2.22, 95%CI 1.69-2.91, P=8.3×10-9). There was no evidence of an association between presence of erosive damage and smoking status or carriage of PTPN22 risk alleles.
Conclusions This meta-analysis indicates that both smoking and having the PTPN22 risk allele affect the risk of ACPA positivity, however, neither PTPN22 nor smoking is associated with erosive damage.
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Disclosure of Interest None Declared