Background CD3 zeta chain (CD3 zeta) is a member of T cell antigen receptor CD3 complex and has crucial role in proximal signal transduction after peptide antigen recognition. CD3 deficiency and loss of immunoreceptor tyrosine-based activation motif (ITAM) domain in CD3 zeta can lead to autoimmune diseases in mice. Furthermore, previous reports including us have clearly shown that CD3 zeta expression was decreased in peripheral blood T cells from lupus patients. On the other hand, a few reports on CD3 zeta in rheumatoid arthritis (RA) were controversial and its role remains still unclear.
Objectives Aim of this study is to investigate the role of CD3 zeta in RA. Especially, we focused on the effect on the expression of CD3 zeta by biologic DMARDs and methotrexate (MTX).
Methods In this study, 33 patients who had visited to our division were diagnosed as the 2010 ACR-EULAR classification criteria for RA and 8 healthy subjects were enrolled. The patients’ background, clinical and laboratory features were also evaluated. Peripheral blood T cells were obtained from the patients with RA at the point of start and 24 weeks after treatment. Protein expression of CD3 zeta was measured by immunoblot analysis by anti-CD3 specific monoclonal antibody.
Results Mean age was 60.2 years old and 72.7% of patients were female. All of the patients had active diseases at the start of treatment. Disease activity score (DAS28-ESR) were 5.16±1.37 and simplified disease activity index (SDAI) was also high, 26.1±14.2 (Mean ± SD). Twenty-six patients were treated with biologic DMARDs (infliximab (IFX): 11 cases, tocilizumab (TCZ): 9, abatacept (ABT): 3, adalimumab (ADA): 2, and etanercept (ETN): 1). Residual 7 patients were treated with MTX alone for 24 weeks. The protein expression level of CD3 zeta was significantly decreased in 29/33 (87.9%) of RA patients as compared with that in healthy subjects (cutoff value were set as mean – 2SD in healthy subject). In average, 68% reduction of CD3 zeta were observed in RA patients (p<0.05). Next, comparing to clinical indicators, DAS28-ESR, SDAI, and dose of concomitant steroid administration were not significantly correlating to CD3 zeta at the start. However, CD3 zeta expression after treatment is restored to nearly same level as healthy subjects in half of them. The recovery level of CD3 zeta did not correlated to DAS28-ESR directly. The recovery was observed in all treatment groups. Compared with agents, interestingly IFX treatment made 3.3 times as high recovery as MTX treatment.
Conclusions Decreased peripheral CD3 zeta protein expression was observed in active RA patients. These effects can be restored by various biologic DMARDs and MTX. Such new insights on CD3 zeta may give a clue for discovery of fundamental pathogenesis on RA.
Disclosure of Interest None Declared