Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis
Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis
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DOI：
10.1191/1352458506ms1241oa
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发表时间：
2006-02-01
影响因子：
5.8
通讯作者：
Baricordi, OR
中科院分区：
文献类型：
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作者：
Fainardi, E;Rizzo, R;Baricordi, OR
本研究的目的是进一步了解经典可溶性HLA-A、B和C1 a类（sHLA-1）和非经典可溶性HLA-G1 b类（sHLA-G）分子在多发性硬化（MS）免疫调节中的作用。我们通过酶联免疫吸附试验（ELISA）技术评估了69例复发缓解型（RR）、21例继发性进展型（SP）和13例原发性进展型（PP）MS患者的鞘内合成、脑脊液（CSF）和血清sHLA-1和sHLA-G水平，根据疾病活动的临床和磁共振成像（MRI）证据进行分层。我们还测试了91例其他炎性神经系统疾病（OIND）和92例非炎性神经系统疾病（NIND）患者作为神经系统对照。82名健康志愿者作为sHLA-1和sHLA-G测定的进一步对照。MS患者鞘内sHLA-1和sHLA-G特异性指标的表达明显高于对照组（P < 0.01）。鞘内合成sHLA-1在临床上是普遍存在的。（P < 0.02）和MRI活动（P < 0.001）MS，而CSF限制性释放的sHLA-G在临床上占主导地位，（P < 0.01）和MRI稳定临床活动期MS患者血清sHLA-1水平较低（P < 0.001），MRI活动期脑脊液中阳性率高（P < 0.001）（P < 0.01）MS。相反，临床稳定期MS患者血清中sHLA-G浓度明显降低（P < 0.01），MRI非活动期MS患者脑脊液中sHLA-G浓度明显升高（P < 0.001）。在没有临床和MRI活动证据的患者中，CSF和血清浓度与鞘内sHLA-1和sHLA-G合成之间观察到的负相关趋势证实了CSF和血清浓度中sHLA-1和sHLA-G的鞘内产生和波动在MS中是相互的。我们的结果表明，在MS中，在经典sHLA-1和非经典sHLA-G产物之间可能存在以相反方向调节MRI和临床疾病活性的平衡。
The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class 1a (sHLA-1) and non-classical soluble HLA-G class 1b (sHLA-G) molecules in immune clysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-1 and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with noninflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-1 and sHLA-G determinations. An intrathecal production of sHLA-1 and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (P < 0.01). An intrathecal synthesis of sHLA-1 was prevalent in clinically (P < 0.02) and MRI active (P < 0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (P < 0.01) and MRI stable (P < 0.001) MS. sHLA-1 levels were low in the serum of clinically active (P < 0.001) and high in the CSF of MRI active (P < 0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (P < 0.01) and increased in the CSF of MRI inactive MS (P < 0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-1 and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-1 and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-1 and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.