研究证实:链球菌DNA成分可能导致银屑病发病，其研究论文《链球菌抗原中的细菌DNA成分增强寻常型银屑病患者外周血单核细胞（PBMC）的增殖和活化》于2009年7月16日在线发表在《皮肤病学研究杂志》（J Investigat Dermatol）上。

   通过研究链球菌DNA对于银屑病患者免疫细胞增殖、活化以及各种细胞因子分泌水平变化的影响后发现，与健康人群相比，银屑病患者PBMC经过链球菌抗原（SA）刺激后，具有更强的增殖反应能力。研究者使用DNA酶-I去除链球菌抗原中的核酸成分后获得去除核酸成分的链球菌抗原（non-NASA）。用non-NASA刺激患者PBMC后的增殖效应显著低于SA刺激组。

   此外，non-NASA与SA刺激相比，T细胞（包括表达皮肤归巢淋巴细胞相关抗原的T细胞）表达CD69水平和PBMC分泌α干扰素（IFN-α）水平显著降低。而对于non-NASA刺激引起的患者T细胞活化水平和IFN-α分泌量下降，如果在其刺激中同时加入人工合成的CpG-A，则可以恢复到单独SA刺激水平，CpG-A的作用正是模拟了链球菌的DNA成分。

   二组刺激相比，B细胞表面活化标志CD86表达水平和γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）分泌量并没有明显改变；但在刺激同时加入人工合成的CpG-B后CD86的表达水平显著升高。

   该研究通过揭示链球菌抗原（尤其是链球菌DNA）的生物学功能，发现non-NASA相比SA可显著降低银屑病患者PBMC增殖和T细胞活化，提示链球菌DNA可辅助活化致病性T细胞，诱导银屑病的发生与发展。

Journal of Investigative 16 July 2009; doi: 10.1038/jid.2009.153

Enhanced Proliferation and Activation of Peripheral Blood Mononuclear Cells in Patients with Psoriasis Vulgaris Mediated by Streptococcal Antigen with Bacterial DNA

Yi-Hua Cai1, Zhi-Yong Lu1, Ruo-Fei Shi1, Feng Xue1, Xiao-Ying Chen1, Meng Pan1, Wei-Ru Yuan1, Han Xu1, Wei-Ping Li1 and Jie Zheng1

1Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Streptococcal infection is believed to have an intimate relationship with psoriasis, although the pathogenic role of streptococcal DNA is not fully understood. To gain a clearer understanding of these dynamics, we investigated the effect of streptococcal DNA on lymphocyte proliferation and activation as well as cytokine secretion in psoriasis. Peripheral blood mononuclear cells (PBMCs) from psoriatic patients had higher proliferative responses upon stimulation by streptococcal antigen (SA) when compared with those from healthy individuals. Strikingly, this enhanced proliferation of PBMCs was attenuated after administration of SA treated with DNase-I. In addition, CD69 expression levels on T cells, including skin-homing lymphocyte cutaneous lymphocyte-associated antigen positive T cells, and IFN-α secretion by PBMCs were also attenuated in patients after stimulation with SA without nucleic acid (non–nucleic acid SA, non-NASA) compared with stimulation with untreated SA. However, activation marker CD86 expression levels on B cells as well as the secretion of IFN-α and tumor necrosis factor (TNF)-α following stimulation with SA or non-NASA were not significantly altered. Interestingly, the attenuated T-cell activation and IFN-α secretion in psoriatic patients could be reconstituted when stimulated by non-NASA combined with synthetic CpG-A, but not when combined with synthetic CpG-B. This study demonstrates the integral function of SA, particularly streptococcal DNA, in the pathogenesis of psoriasis.