Background/Purpose: Rheumatoid factor (RF) is produced as a result of polyclonal B cell activation, but the reasons for its production are still unknown. RF positivity can be seen in several diseases other than rheumatoid arthritis (RA), such as other rheumatic diseases and viral infection as well as in normal individuals. It was reported that RF was present in hepatitis B virus (HBV) infection. However, the types of antigens or antibodies of HBV and the hepatitis B viral load that play an important role in the development of RF remain obscure. In this study, we investigated the RF positive rates and titers of RF according to various HBV infection status and vaccination, and the relationship between the titers of RF and serum HBV DNA levels in HBV endemic areas.

Methods: The subjects were 13,670 individuals who visited the Severance Hospital Health Promotion Center in Seoul, Korea, for routine health check-up from January 2004 to December 2004. The samples were tested for RF (IgM type) and HBV infection by screening for the presence of HBsAg, anti-HBs (IgG type), and anti-HBc (IgG type). The HBeAg, anti-HBe (IgG type), and HBV DNA were analyzed in subjects positive for HBsAg. The RF positive rates and the titers of RF were evaluated based on the presence of each HBV viral marker, and correlation between the titers of RF and the serum HBV DNA levels was assessed.

Results: RF was positive in 3.5% of all subjects, and HBsAg was positive in 4.3%. HBsAg was positive in 21.7% of RF positive subjects. The HBsAg positive group had higher RF positive rate than negative group (17.5% vs 2.9%, p < 0.001). The RF positive rate was lower in those who had anti-HBs after HBV vaccination than in HBsAg positive subjects (2.7% vs 17.5%, p < 0.001). Among HBsAg positive subjects, the RF positive rate in the anti-HBs positive group was higher than that in the anti-HBs negative group (30.3% vs 16.8%, p = 0.047). However, there was no significant difference in the RF positive rate between the anti-HBc positive and negative groups, and HBeAg positive and negative groups. In multiple logistic regression analysis, the RF positive rate was increased in positive HBsAg (PR = 7.82, 95% CI 5.74 to 10.67, p < 0.001), female sex (PR = 1.21, 95% CI 1.01 to 1.46, p = 0.042) and older age (PR = 1.01, 95% CI 1.001 to 1.019, p = 0.027). Among the RF positive patients, the titer of RF in HBsAg positive patients were higher than those in HBsAg negative patients (159.7 ± 217.1 IU/mL vs 83.0 ± 179.2 IU/mL, p = 0.001). However, there were no significant differences in the titer of RF between anti-HBc positive and negative groups, and between HBeAg positive and negative groups. The load of HBV DNA may be closely correlated with the titer of RF in patients with chronic hepatitis B (r = 0.508, p = 0.005).

Conclusion: HBV infection is an important cause of the false positive RF in HBV endemic area. Especially hepatitis B viral load may be associated with the titer of RF. Therefore, HBV vaccination may decrease the risk of RF formation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-implication-of-rheumatoid-factor-formation-according-to-various-hepatitis-b-virus-infection-status-and-vaccination/