Background It is well known that levels of IL-6 and its soluble receptor (IL-6Rs) correlate with the disease activity in patients with rheumatoid arthritis (RA). The C allele of the single nucleotide polymorphism (SNP) rs2228145 in the IL-6R gene drives, through an alternative splicing mRNA, to higher levels of soluble IL-6R. This soluble form of the receptor can amplifying the inflammatory response mediated by IL-6.
Objectives To analyse whether the genotype of rs2228145 can impact the outcome of patients with early arthritis (EA).
Methods We analysed data from 261 patients included in our EA registry with a two-year prospective follow-up. According to a scheduled protocol, sociodemographic variables (gender, age, smoking, education, etc.) along with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA) were collected at baseline; clinical and laboratory variables (global patient’s and physician’s disease assessment, tender and swollen joint counts, HAQ disability questionnaire, erythrocyte sedimentation rate, C reactive protein [CRP], dosage and type medications prescribed) were recorded at each visit. IL-6 levels were determined by an ultrasensitive ELISA kit (R & D Systems). The genotyping of rs2228145 in IL-6R gene was performed using specific Taqman probes (Applied Biosystems). To assess the effect of independent variables on the level of disease activity (remission to high activity) at the end of follow-up we developed an ordered logistic regression with the command ologit of Stata 10.1 for Windows (StataCorp LP, College Station, TX, USA).
Results Of the 261 patients analysed, 75% were women, with a median [p25-p75] age at disease onset of 53.63 [42.79 to 66.43] years and an evolution time at the inclusion in the registry of 5.63 [3.6 -8.5] months. 46.3% of the patients were positive for RF and 43.02% for ACPA. The variables significantly associated with an increased level of disease activity were female gender (p=0.02), having age between 45-65 years compared to patients younger than 45 years (p<0.001) and high activity at the baseline visit (p=0.001). Moreover, EA patients that were homozygous for allele C (CC) in the SNP rs2228145 in IL-6R alpha chain, showed a higher DAS28 at 2 years (p=0.039) compared with patients homozygous for the ancestral allele (AA). Heterozygous patients (AC) displayed a trend, although not statistically significant, to maintain a high DAS28 (p=0.063) compared to patients homozygous for the ancestral allele (AA).
Conclusions Conclusion: The presence of the C allele of rs2228145 in the IL-6R gene might be a biomarker of poor prognosis in patients with EA. However, our findings should be validated in other EA populations.
This work was partially funded by the program RETICS, RD080075 (Riera), FIS 080754 of the Health Institute Carlos III (ISCIII) and research support from Roche Pharmaceuticals (Unrestricted grant)
Disclosure of Interest None Declared