JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications. OBJECTIVE: We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls. RESULTS: Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047). CONCLUSION: Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.

Retrospective study on effect of antinuclear antibody, extractable nuclear antigen and antineutrophil cytoplasmic antibody on clinical manifestation and cerebrospinal fluid characteristics of neuromyelitis optica / 中华神经科杂志

Objective To explore the effect of antinuclear antibody ( ANA+dsDNA),extractable nuclear antigen (ENA) and antineutrophil cytoplasmic antibody (ANCA) on the clinical manifestation and cerebrospinal fluid characteristics of neuromyelitis optica (NMO).Methods All 41 patients with NMO in PUMC hospital from 1985 to 2009 were retrospectively reviewed.All patients underwent examination of serum ANA+dsDNA,ENA and ANCA.Fourteen positive-autoantibody patients were compared with 27negative-autoantibody patients in gender,onset age,duration,relapse ratio,first demyelination event,the extent of optic neuritis and myelitis,EDSS,CSF protein,WBC,Oligoclonal band, 24 hours IgG index and myelin basic protein.Results The 14 NMO patients (34.1%) had positive non-organ-specific antibodies.NMO patients who had negative autoantibodies were compared with NMO patients with positive autoantibodies with significantly higher EDSS (the EDSS score were 4.5 and 2.5 respectively,U=92.5,P=0.008),more complete damage of spinal cord (3/14 vs 0/27, x2=6.736, P=0.0095) and tended to have higher visual Function Scale in remitting phase.There was no significant difference on the gender,onset age,duration,relapse ratio,first demyelination event.The positive-autoantibody patients had higher CSF WBC (2.0 vs 0,U=68.0,P=0.007) and tended to have lower 24 hours IgG index (-8.663 vs 0.163,U=30.0,P=0.053).There was no significant difference in CSF protein,MBP and OB.Conclusion NMO patients with positive autoantibodies have more severe intrathecal autoimmune inflammatory and disability,so they might need more intensive treatment.