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Objective.In patients with systemic lupus erythematosus (SLE), evidence suggests that most vaccines (except live-virus vaccines) are safe, although antibody response may be reduced. This substudy from the phase III, randomized, double-blind, placebo-controlled BLISS-76 trial evaluated the effects of belimumab on preexisting antibody levels against pneumococcal, tetanus, and influenza antigens in patients with SLE.Methods.In BLISS-76, patients with autoantibody-positive, active SLE were treated with placebo or belimumab 1 or 10 mg/kg every 2 weeks for 28 days and every 28 days thereafter, plus standard SLE therapy, for 76 weeks. This analysis included a subset of patients who had received pneumococcal or tetanus vaccine within 5 years or influenza vaccine within 1 year of study participation. Antibodies to vaccine antigens were tested at baseline and Week 52, and percentage changes in antibody levels from baseline and proportions of patients maintaining levels at Week 52 were assessed. Antibody titers were also assessed in a small number of patients vaccinated during the study.Results.Consistent with preservation of the memory B cell compartment with belimumab treatment, the proportions of patients maintaining antibody responses to pneumococcal, tetanus, and influenza antigens were not reduced. In a small group receiving influenza vaccine on study, antibody responses were frequently lower with belimumab, although titer levels were > 1:10 in all patients treated with 10 mg/kg and in the majority treated with 1 mg/kg.Conclusion.Treatment with belimumab did not affect the ability of patients with SLE to maintain antibody titers to previous pneumococcal, tetanus, and influenza immunizations. [ClinicalTrials.gov registration number NCT 00410384]

Objective Although blood bank–based studies have shown that rheumatoid arthritis (RA)–related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5‐year PPV of serum IgM rheumatoid factor (IgM‐RF) and anti–cyclic citrullinated peptide (anti‐CCP) for the development of RA among healthy relatives of patients with RA. Methods Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants’ medical history was obtained, and serum levels of IgM‐RF and anti‐CCP antibodies were determined (by nephelometry and second‐generation anti‐CCP enzyme‐linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in‐office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. Results Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti–CCP‐2 and RF, 12 (1.5%) only for anti–CCP‐2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5‐year followup (3,313 person‐years for the seronegative group and 60.8 person‐years for the anti–CCP‐2–positive group). The PPV was 64% when both anti–CCP‐2 and RF were positive and 58% when only anti–CCP‐2 was positive. Offspring of patients with RA had an independent 3‐fold increased risk of developing RA. Conclusion Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.

BackgroundThe role of adipose tissue in RA pathogenesis has been acknowledged since the high frequency of dyslipidemia and insulin resistance in these patients. Leptin, a pleiotropic adipokine, has been associated with inflammation markers and articular damage in RA and the anti-citrullinated protein antibodies. Notwithstanding, these findings have not been constant across different populations. These points towards that single nucleotide polymorphism (SNP) in leptin and its receptor might influence the participation of this adipokine in RA pathogenesis.ObjectivesTo determine the association of the SNPs LEP -2548 G>A and LEPR 668 A>G with adiposity, metabolic and inflammation markers in RA patients.MethodsWe enrolled 116 patients with RA (ACR 1987) matched with 133 control subjects by age, gender, and body mass index (BMI). Subjects were evaluated for fat mass and skinfold thickness. Also, serum glucose, insulin, lipid profile, serum leptin (sLep), soluble leptin receptor, TNFa. In patients with RA we evaluated disease activity and anti-CCP. Genotypes of LEP -2548 G>A and LEPR 668 A>G were determined by PCR-RFPL using HhaI and MspI restriction enzymes.ResultsThere was no difference in genotypes distribution of LEP -2548 G>A and LEPR 668 A>G between RA and control. LEPR 668 G allele was associated with higher anti-CCP titers and disease activity score compared to LEPR 668A/A homozygotes, 4.2±1.7 vs. 3.46±1.2 P=0.012. LEP -2548A allele was associated with younger age of RA diagnosis vs. G/G homozygotes, 35.9±11.5 vs. 41.8±13.9 years old (P =0.045). OR for diagnosis before 40 years old was 2.7 (CI95% 1.04 – 7.45).Conclusions LEP -2548 G>A is related with a younger age at diagnosis of RA and LEPR 668 G/G was associated with increased anti-CCP titers and disease activity. This suggests that there is an additive effect between chronic inflammation of RA and obesity were leptin may favor humoral immune response against citrullinated proteins and influence the severity of RA.In preobese and obese patients with RA anti-CCP (+) there is an increased sLep production. LEP -2548 G>A is related with a younger age at diagnosis of RA and LEPR 668 G/G was associated with increased anti-CCP titers and disease activity. These suggests that there is an additive effect between chronic inflammation of RA and obesity were leptin may favors humoral immune response against citrullinated proteins and influence the severity of RA.Disclosure of InterestNone declared