We investigate whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. A HSP70-2 PstI polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified genomic DNA in 90 SLE patients and 117 controls. The PstI site containing allele (B) was significantly increased in SLE patients compared to healthy controls. This was due to a significant increase in the BB homozygous genotype in patients, particularly in those with diffuse proliferative nephritis. Neither allelic nor genotypic differences were detected when compared by the presence or absence of DR3. The HSP70-2 B allele seems tightly linked to the human leucocyte antigen (HLA) haplotypes carrying susceptibility to SLE in our population. An independent role for this gene cannot be confirmed due to its linkage with HLA DR3.

BackgroundABP 501 has been approved by the US FDA as the first biosimilar to the fully human recombinant monoclonal antibody, adalimumab. Totality of evidence to date suggests that ABP 501 is highly similar to adalimumab. Subjects receiving either ABP 501 or adalimumab in the active-controlled, comparative, pivotal phase 3 study in rheumatoid arthritis (parent study) continued on to this open-label extension (OLE) study if they had completed the final week 26 visit of that study.ObjectivesTo describe the safety, immunogenicity, and efficacy outcomes of ABP 501 in the OLE study.MethodsSubjects who completed the parent study were screened and were included if they met the eligibility requirements. All subjects included in the OLE were treated with ABP 501 40 mg subcutaneously every other week for 68 weeks followed by disease assessments at week 70 and the follow-up safety assessment at week 72 (or early termination). Data were summarized descriptively and no inferential analyses were performed.ResultsOf the 467 subjects enrolled in the OLE study, 466 were treated with ABP 501. Of these, 237 transitioned from the adalimumab arm of the parent study; 412/467 completed the study. Demographics and disease characteristics were balanced between subjects who transitioned from adalimumab and those who continued on ABP 501 from the parent study. Overall, the incidence of treatment-emergent adverse events (TEAEs) was 63.7% (297/466) and that of grade ≥3 TEAEs was 9.0% (42/466); incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). TEAEs with incidence ≥5% were nasopharyngitis (9.2%), upper respiratory tract infection (8.6%), bronchitis (6.4%), rheumatoid arthritis (6.2%), hypertension (4.7%), and pharyngitis (4.1%). The incidence of serious adverse events was 9.9% (46/466). Most common TEAEs of interest were infections (40.8%), liver enzyme elevations (5.4%), and hypersensitivity (4.3%).Overall, 18.2% (85/466) of subjects developed binding antidrug antibodies (ADAs) and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The rates of ADA formation were similar between subjects who transitioned from adalimumab and those who continued on ABP 501.The ACR20 response rate (using the parent study baseline) was 73.3% (340/464) at the OLE study baseline, 77.6% (361/465) at week 4, 74.2% (336/453) at week 24, 77.6% (337/434) at week 48, and 78.8% (327/415) at week 70. The overall mean DAS28-CRP change from parent study baseline was −2.25 (n=440) at the OLE study baseline, −2.36 (n=463) at week 4, −2.41 (n=450) at week 24, −2.55 at week 48 (n=433), and –2.60 at week 70 (n=412).ConclusionsIn this OLE study of ABP 501, efficacy documented in the parent study was maintained with no new safety findings. Long-term safety, immunogenicity, and efficacy results were similar between subjects who transitioned from adalimumab and those who continued on ABP 501 from the parent study.Disclosure of InterestS. Cohen Consultant for: Amgen Inc, J. L. Pablos Consultant for: Amgen Inc, H. Wang Shareholder of: ...

We confirm a preferential accumulation of CCR5-expressing lymphocytes into RA-SF. However, the chemotactic responses of lymphocytes to RA-SF were not dependent on a functional CCR5 receptor, suggesting that CCR5 is a marker of a lymphocyte subset rather than a specific mediator of chemotactic responses to chemokines in RA-SF.

Background and objectives The functional relevance of synovial ectopic lymphoid neogenesis (ELN) in rheumatoid arthritis (RA) remains unknown. As ELN correlates with the degree of tissue inflammation we investigated whether ELN was associated with specific cytokine profiles. Materials and methods Paired synovial tissue (ST) (n = 63) and fluid (SF) (n = 44) was obtained from the inflamed knee joints of RA patients. Synovial inflammation and ELN was determined by immunohistology. CD21L was used as molecular marker of ELN. Cytokine expression was determined by ELISA and quantitative PCR in SF and ST, respectively. Results 48% of ST displayed ELN by histology. ELN+ samples had increased T and B lymphocyte infiltration (p < 0.001) and CD21L expression (p = 0.014). SF analysis showed higher expression of IL-23 (p = 0.018) and IL-17F (p = 0.028) in ELN+ versus ELN- samples, with a similar trend for IL-22 (p = 0.070). Other cytokines, including IL-17A, IL-6, TNF-a, Th1 cytokines and Th2 cytokines, were not different. In ST, IL-23 (p = 0.030) mRNA levels were increased in ELN+ samples. Moreover, CD21L expression as molecular marker of ELN correlated significantly with mRNA expression of IL-23 (r = 0.70), IL-17F (r = 0.42), IL-21 (r = 0.30) and IL-22 (r = 0.33), but not IL-17A. The strong correlation between CD21L and IL-23, IL-17F, IL-21 end IL-22 was confirmed in an independent RA ST sample set (n = 36). IFNg and IL-2, but not IL-6 and TNF-α, also showed some correlation with CD21L expression. Conclusion Synovial ELN in RA is strongly associated with increased expression of IL-23/IL-17-related cytokines. Whether patients depicting synovial ELN respond differently to therapeutic targeting of this pathway remains to be determined.

The objective of this study was to investigate whether an octamer transcription factor gene (OTF3) located within the MHC region of chromosome 6 is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. An OTF3 HindIII polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction amplified genomic DNA in 69 patients with SLE and 60 controls. No differences in the OTF3 allelic or genotypic distribution between healthy controls and patients with SLE were found. In the group of patients with diffuse proliferative glomerulonephritis, where we have previously detected the strongest MHC association, we did not observe OTF3 linkage either. In conclusion, the OTF3 gene does not appear to be associated with SLE in the Spanish population. This might be due to the distance of the gene from the HLA class II-III region where more relevant autoimmune-related genes are located.