Willeke P, Schotte H, Schlüter B, Erren M, Becker H, Dyong A, Mickholz E, Domschke W, Gaubitz M
Department of Medicine B, Westphalian Wilhelms-University, Muenster, Germany.
Ann Rheum Dis. 2003 Apr;62(4):359-62. doi: 10.1136/ard.62.4.359.
To study systemic alterations of cytokine secreting peripheral blood mononuclear cells (PBMC) in primary Sjögren's syndrome (pSS) and their relation to common clinical and immunological manifestations of this disease.
PBMC spontaneously secreting tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and interleukin 6 (IL6) were assessed by enzyme linked immunospot (ELISPOT) analysis in a cohort of 31 patients with pSS fulfilling the modified European classification criteria. Nineteen healthy volunteers served as controls. ELISPOT results were correlated with glandular and extraglandular manifestations and autoantibody titres-that is, rheumatoid factor (RF) isotypes, anti-Ro/SS-A, anti-La/SS-B as determined by an enzyme linked immunosorbent assay (ELISA) technique.
The number of TNFalpha and IL1beta secreting cells was significantly higher in patients with pSS than in controls. No differences were detected in the number of IL6 secreting PBMC. Patients with recurrent parotid swelling (RPS) had a significantly increased number of IL1beta secreting PBMC. Moreover, the number of IL1beta secreting PBMC correlated with the disease duration (r(s)=0.479; p<0.01) and with the concentration of IgM RF (r(s)=0.63; p<0.01) and IgG RF (r(s)=0.42; p<0.05). Other autoantibodies did not correlate with cytokine secreting PBMC.
The increased systemic secretion of IL1beta and TNFalpha in patients with pSS points to a pathogenic impact of these cytokines in this autoimmune disease. In particular the correlation of IL1beta secreting PBMC with RPS and RF production indicates that IL1beta is a crucial regulator in the development of local and systemic disease manifestations.
研究原发性干燥综合征(pSS)中分泌细胞因子的外周血单个核细胞(PBMC)的全身改变及其与该疾病常见临床和免疫学表现的关系。
采用酶联免疫斑点(ELISPOT)分析法,对31例符合改良欧洲分类标准的pSS患者队列中自发分泌肿瘤坏死因子α(TNFα)、白细胞介素1β(IL1β)和白细胞介素6(IL6)的PBMC进行评估。19名健康志愿者作为对照。ELISPOT结果与腺体和腺体外表现以及自身抗体滴度相关,即通过酶联免疫吸附测定(ELISA)技术测定的类风湿因子(RF)同种型、抗Ro/SS-A、抗La/SS-B。
pSS患者中分泌TNFα和IL1β的细胞数量显著高于对照组。分泌IL6的PBMC数量未检测到差异。复发性腮腺肿胀(RPS)患者分泌IL1β的PBMC数量显著增加。此外,分泌IL1β的PBMC数量与疾病持续时间(r(s)=0.479;p<0.01)以及IgM RF浓度(r(s)=0.63;p<0.01)和IgG RF浓度(r(s)=0.42;p<0.05)相关。其他自身抗体与分泌细胞因子的PBMC无关。
pSS患者中IL1β和TNFα的全身分泌增加表明这些细胞因子在这种自身免疫性疾病中具有致病作用。特别是分泌IL1β的PBMC与RPS和RF产生之间的相关性表明,IL1β是局部和全身疾病表现发展中的关键调节因子。