Wang Yan, Virji Adi S, Howard Paul, Sayani Yaseen, Zhang Jianghong, Achu Paul, McArthur Carole
Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
Arch Oral Biol. 2006 Jul;51(7):558-66. doi: 10.1016/j.archoralbio.2005.11.008. Epub 2006 Jan 6.
Sjögren's syndrome (SS) is a systemic autoimmune disease which targets the exocrine glands and is associated with autoantibodies. The mechanism of salivary gland destruction or autoantibody production is poorly understood but it is increasingly accepted that apoptosis plays a role.
The objective of this study is to demonstrate the presence of cleaved alpha-fodrin autoantigen and apoptosis in the salivary glands of patients with primary Sjögren's syndrome.
18 patients with primary Sjögren's syndrome provided tissues from a labial salivary gland biopsy. Using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assays to detect DNA fragmentation followed by sequential immunoperoxidase assays in the same patient biopsy to detect cleaved alpha-fodrin, Poly(ADP-ribose) polymerase (PARP), and caspase-3, we show a co-localisation between apoptotic markers and disease.
Co-localisation of cleaved alpha-fodrin, PARP and caspase-3 expression was demonstrated primarily in the ducts along with DNA fragmentation in 16/18 salivary gland biopsies from Sjögren's syndrome patients. None of these apoptotic markers was strongly expressed in healthy tissues.
Apoptotic signals may provide useful therapeutic targets and cleaved alpha-fodrin may prove to be a marker of disease in primary Sjögren's syndrome. Further studies are required to ascertain the specific association of cleaved alpha-fodrin with primary and secondary Sjögren's syndrome.
干燥综合征(SS)是一种全身性自身免疫性疾病,主要累及外分泌腺,并与自身抗体有关。唾液腺破坏或自身抗体产生的机制尚不清楚,但越来越多的人认为细胞凋亡在其中起作用。
本研究旨在证实原发性干燥综合征患者唾液腺中存在裂解的α- fodrin自身抗原和细胞凋亡现象。
18例原发性干燥综合征患者提供了唇腺活检组织。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测DNA片段化,随后在同一患者活检组织中进行连续免疫过氧化物酶检测,以检测裂解的α- fodrin、聚(ADP - 核糖)聚合酶(PARP)和半胱天冬酶 - 3,结果显示凋亡标志物与疾病之间存在共定位。
在干燥综合征患者的16/18份唾液腺活检组织中,裂解的α- fodrin、PARP和半胱天冬酶 - 3的表达共定位主要出现在导管中,同时伴有DNA片段化。在健康组织中,这些凋亡标志物均未强烈表达。
凋亡信号可能提供有用的治疗靶点,裂解的α- fodrin可能被证明是原发性干燥综合征的疾病标志物。需要进一步研究以确定裂解的α- fodrin与原发性和继发性干燥综合征的具体关联。