Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency

Background The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. Methods In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients. Results Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. Conclusions Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.

Association between HLA-DRB1* allele polymorphism and caries susceptibility in Han Chinese children and adolescents in the Xinjiang Uygur Autonomous Region

Objective The rate of caries and the mean number of decayed, missing, or filled teeth were reported to be significantly higher in children in the Xinjiang Uygur Autonomous Region than in children in eastern China. Little is known regarding the genetic basis of caries among residents of the Xinjiang Uygur Autonomous Region. This study investigated the association between HLA-DRB1 alleles and caries susceptibility in Han Chinese children and adolescents in the Xinjiang Uygur Autonomous Region. Methods HLA-DRB1 allele frequency was assessed in DNA samples from buccal swabs of 42 patients with caries and 123 healthy control participants using a polymerase chain reaction method with sequence-specific primers. The chi-squared test or Fisher’s exact test, followed by Bonferroni correction, was used to calculate differences in allele frequencies between groups. Results Compared with the healthy controls, the allele frequency of HLA-DRB1*13 was significantly higher in patients with caries in the Xinjiang Uygur Autonomous Region (35.71% vs. 18.70%). The allele frequency of HLA-DRB1* 09 was significantly lower in patients with caries than in healthy controls (4.76% vs. 25.20%). Conclusions HLA-DRB1* 13 alleles could confer greater caries susceptibility, whereas HLA-DRB1* 09 could be protective against caries pathogenesis, in Han Chinese children in the Xinjiang Uygur Autonomous Region.