Pathogenetic associations of anti-ribosomal P protein antibody titres and its subclasses in patients with systemic lupus erythematosus.

ABSTRACT

OBJECTIVES: We evaluated the association between anti-ribosomal P antibody (anti-RibP) titres and disease activity in Japanese systemic lupus erythematosus (SLE) patients. METHODS: Eighty patients admitted and treated in Niigata University Hospital for new-onset or flare-up of SLE were included in this retrospective cross-sectional study. Clinical data were obtained from medical records at admission. Anti-RibP index, and cytokine and tryptophan metabolite levels were determined by ELISA. RESULTS: Of the 80 SLE patients, 30 had anti-RibP. Anti-RibP presence was associated with a greater prevalence of skin rash and more severe inflammatory responses, demonstrated by higher inflammatory cytokine levels, hypocomplementemia, and accelerated tryptophan metabolism, in younger patients. The serum anti-RibP index correlated with age at diagnosis, clinical indicators, initial prednisolone dose, and cytokines and tryptophan metabolite levels in univariate analysis. Multivariate analysis showed the anti-RibP index was independently associated with initial prednisolone dose and prevalence of skin rash. Anti-RibP IgG were mainly IgG2 and IgG3 subclasses, and anti-RibP IgG3 was associated with hypocomplementemia, higher disease activity score, accelerated kynurenine pathway activity, and higher proinflammatory cytokine production. The coexistence of anti-dsDNA IgG and anti-RibP IgG2 or IgG3 accompanied higher IL-10 and IFN-α2 levels; furthermore, anti-RibP IgG3 coexistence with anti-dsDNA antibody contributed to the requirement for higher initial prednisolone doses and accelerated kynurenine pathway activity. CONCLUSION: Anti-RibP was associated with clinical manifestations and parameters in SLE, and its index might be a useful indicator of disease severity. Anti-RibP IgG3 was the IgG subclass most strongly associated with the pathogenesis of SLE.