THU0361 Characterisation of novel autoantibodies to ahnak1 specifically presented in patients with systemic lupus erythematosus
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Abstract:
Background
Aberrant activation of T cells has been considered to play important roles for pathogenesis of SLE. In T cells activation, calcium signalling is essential for the process. Interestingly, T cells of SLE patients have been reported to show several abnormalities of calcium signalling. In the present study, we postulated that patients with SLE may target calcium signaling-related molecules as autoantigen as autoantibodies to these molecules are potentially capable of interfering with calcium signalling through binding to these molecules localised at the plasma membrane eventually resulting in abnormal T cells activation in SLE. Regarding to the calcium signaling-related molecules, recent studies have shown that AHNAK1 is predominantly expressed in CD4 +T cells of cell membrane and cytoplasm. Moreover, AHNAK1 is known to play significant roles for regulating of calcium signalling at T cells activation through its ability to localise calcium channels properly at the plasma membrane as scaffold protein. Therefore, we verify whether autoimmune response to AHNAK1 is elicited in SLE.Objectives
The present study was conducted to clarify whether autoantibodies to AHNAK-1 are produced in SLE compared with other connective tissue diseases and normal healthy controls (NHCs).Methods
The Patients sera consisting of SLE (n=59), other connective tissue diseases (PM/DM; n=40, SSc; n=40, SS; n=30, MCTD; n=30, and RA; n=30) and NHCs (n=115) were used in the present study. Immunoreactivitiy against AHNAK1 recombinant antigens was evaluated by ELISA. AHNAK1 mRNA expression in peripheral blood mononuclear cells (PBMCs) was evaluated by quantitative RT-PCR. Indirect immunofluorescence (IIF) staining using monoclonal anti-AHNAK1 antibodies in combination with the patient's sera containing anti-AHNAK1 antibodies was evaluated using HEp-2 substrate. The experimental data were statistically analysed using the Mann–Whitney U-test or Chi-square test, and differences with P-values<0.05 were considered to be significant.Results
Immunoreactivity against AHNAK1 was significantly elevated in SLE patients compared to both NHCs and other connective tissue diseases. Significant elevation of AHNAK1 mRNA expression was observed in PBMC of SLE patients compared to NHCs. Among 17 SLE patients with anti AHNAK1 antibodies positive sera, 4 patients revealed reduction of anti- AHNAK1 antibodies level after the treatment like glucocorticoid or immune suppressive reagents, however, the remaining 13 patients did not show the reduction of serum level pf anti-AHNAK1 antibodies. In clinical profile, lymphopenia was frequently observed in these SLE patients.IIF analysis showed that AHNAK-1 is localised at cell membrane and cytoplasm rather than nucleus.Conclusions
In the present study, we found that autoantibodies to AHNAK1 were significantly observed in sera with SLE compared to both NHCs and other connective tissue diseases. Furthermore, AHNAK1 were enriched in PBMC of SLE patients suggesting antigen driven system may play an important role for this autoantibodies production. Anti-AHNAK1 antibodies may be pathological and play an important role for pathogenesis of SLE because it may possibly alter physiological calcium signalling of T cells through binding to AHNAK1 on cell membrane eventually resulting in aberrant T cells activation in SLE.Disclosure of Interest
None declaredKeywords:
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