van der Linden M W, Westendorp R G, Sturk A, Bergman W, Huizinga T W
Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
J Investig Med. 2000 Sep;48(5):327-34.
Preclinical research suggests that interleukin-10 (IL-10) is associated with susceptibility to and severity of systemic lupus erythematosus. Chronic cutaneous lupus erythematosus is thought to be immunogenetically different from systemic lupus erythematosus. We hypothesized that high innate production of IL-10 underlies systemic but not chronic cutaneous lupus erythematosus.
IL-10 production was determined after endotoxin stimulation of whole-blood samples. In whole-blood samples, disease activity and medication influence the IL-10 production in patients. Therefore, healthy first-degree relatives of patients were evaluated. One hundred sixty-six first-degree relatives of patients with systemic lupus, 50 first-degree relatives of patients with chronic cutaneous lupus, and 133 control persons were studied. Innate IL-10 production of the patient was estimated as the mean IL-10 production of the unaffected relatives. Polymorphisms located -1082, -819, and -592 base pairs relative to the IL-10 gene were typed by allele-specific oligohybridization of polymerase chain reaction-amplified DNA fragments.
IL-10 production was higher in the families of patients with systemic lupus than in the control families (1517 +/- 94 vs 1180 +/- 59 pg/mL; P = 0.003). IL-10 production in the families of patients with chronic cutaneous lupus was similar to that in control families (1216 +/- 82 vs 1180 +/- 59 pg/ml; P = 0.74). IL-10 production was also similar in families of patients with severe compared with nonsevere systemic lupus (P = 1.0). The frequency of -1082/-819/-592 haplotypes GCC, ACC, and ATA was similar among patients and compared with the control persons (P = 0.29).
High innate IL-10 production underlies susceptibility for systemic lupus erythematosus but not the severity of the disease. It is not related to chronic cutaneous lupus erythematosus.
临床前研究表明,白细胞介素-10(IL-10)与系统性红斑狼疮的易感性和严重程度相关。慢性皮肤型红斑狼疮被认为在免疫遗传学上与系统性红斑狼疮不同。我们假设,IL-10的高固有产生是系统性而非慢性皮肤型红斑狼疮的基础。
在内毒素刺激全血样本后测定IL-10的产生。在全血样本中,疾病活动和药物治疗会影响患者体内IL-10的产生。因此,对患者的健康一级亲属进行了评估。研究了166名系统性红斑狼疮患者的一级亲属、50名慢性皮肤型红斑狼疮患者的一级亲属和133名对照者。将患者的固有IL-10产生估计为未受影响亲属的IL-10产生平均值。通过聚合酶链反应扩增DNA片段的等位基因特异性寡杂交对相对于IL-10基因的-1082、-819和-592碱基对处的多态性进行分型。
系统性红斑狼疮患者家庭中的IL-10产生高于对照家庭(1517±94 vs 1180±59 pg/mL;P = 0.003)。慢性皮肤型红斑狼疮患者家庭中的IL-10产生与对照家庭相似(1216±82 vs 1180±59 pg/ml;P = 0.74)。与非重度系统性红斑狼疮患者家庭相比,重度系统性红斑狼疮患者家庭中的IL-10产生也相似(P = 1.0)。患者与对照者之间,-1082/-819/-592单倍型GCC、ACC和ATA的频率相似(P = 0.29)。
高固有IL-10产生是系统性红斑狼疮易感性的基础,但与疾病严重程度无关。它与慢性皮肤型红斑狼疮无关。