The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-alpha activity and low tumor necrosis factor alpha levels in patients with lupus.
The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-alpha activity and low tumor necrosis factor alpha levels in patients with lupus.
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DOI：
10.1002/art.23728
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发表时间：
2008-09
影响因子：
--
通讯作者：
Niewold, Timothy B.
中科院分区：
文献类型：
--
作者：
Kariuki, Silvia N.;Crow, Mary K.;Niewold, Timothy B.
PTPN22 中的 C1858T 多态性与系统性红斑狼疮 (SLE) 以及多种其他自身免疫性疾病的风险相关。我们之前已经证明，高血清干扰素α (IFN-α) 活性是 SLE 的遗传性危险因素，我们假设 PTPN22 风险变异可能会将血清细胞因子谱转变为更高的 IFN-α 活性，从而导致疾病风险。使用功能报告细胞测定法测量 143 名 SLE 患者的 IFN-α，并使用 ELISA 测量 TNF-α。 PTPN22 (C1858T) 中的 rs2476601 SNP 在同一患者中进行了基因分型。使用聚类算法将患者分为四个细胞因子组（IFN-α为主、IFN-α和TNF-α相关、TNF-α为主、IFN-α和TNF-α均较低）。携带 PTPN22 风险等位基因的 SLE 患者比缺乏风险等位基因的患者具有更高的血清 IFN-α 活性 (p=0.027)。风险等位基因携带者的 TNF-α 水平较低 (p=0.030)，与 TNF-α 占主导地位或两种细胞因子均较低的患者相比，风险等位基因在 IFN-α 占主导地位或 IFN-α 和 TNF-α 相关细胞因子谱的患者中更常见 (p=0.002)。 25% 的男性患者携带风险等位基因，而女性患者的这一比例为 10% (p=0.02)，但两性的细胞因子偏差相似。 PTPN22 的自身免疫性疾病风险等位基因与 SLE 患者体内血清细胞因子谱偏向较高的 IFN-α 活性和较低的 TNF-α 相关。这种血清细胞因子模式可能与 PTPN22 风险等位基因相关的其他自身免疫性疾病有关。
The C1858T polymorphism in PTPN22 has been associated with risk of systemic lupus erythematosus (SLE), as well as multiple other autoimmune diseases. We have previously shown that high serum interferon alpha (IFN-α) activity is a heritable risk factor for SLE, and we hypothesized that the PTPN22 risk variant may shift serum cytokine profiles to higher IFN-α activity resulting in risk of disease. IFN-α was measured in 143 SLE patients using a functional reporter cell assay, and TNF-α was measured with ELISA. The rs2476601 SNP in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped using a clustering algorithm into four cytokine groups (IFN-α predominant, IFN-α and TNF-α correlated, TNF-α predominant, and IFN-α and TNF-α both low). SLE patients carrying the risk allele of PTPN22 had higher serum IFN-α activity than patients lacking the risk allele (p=0.027). TNF-α levels were lower in risk allele carriers (p=0.030), and the risk allele was more common in patients with an IFN-α predominant or IFN-α and TNF-α correlated cytokine profile as compared to patients with TNF-α predominance or both cytokines low (p=0.002). 25% of male patients carried the risk allele, compared to 10% of female patients (p=0.02), however cytokine skewing was similar in both sexes. The autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFN-α activity and lower TNF-α in SLE patients in vivo. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele.
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影响因子：
4.9
作者：
Pierer, Matthias;Kaltenhauser, Sylke;Arnold, Sybille;Wahle, Matthias;Baerwald, Christoph;Hantzschel, Holm;Wagner, Ulf
通讯作者：
Wagner, Ulf
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
158.5
作者：
HOOKS, JJ;MOUTSOPOULOS, HM;NOTKINS, AL
通讯作者：
NOTKINS, AL
影响因子：
5.5
作者：
Lee, Y. H.;Rho, Y. H.;Harley, J. B.
通讯作者：
Harley, J. B.
DOI：
10.1073/pnas.0408506102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Palucka, AK;Blanck, JP;Banchereau, J
通讯作者：
Banchereau, J