Fainardi E, Rizzo R, Melchiorri L, Castellazzi M, Paolino E, Tola M R, Granieri E, Baricordi O R
Section of Neurology, Multiple Sclerosis Center, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, Ferrara 1-44100, Italy.
Mult Scler. 2006 Feb;12(1):2-12. doi: 10.1191/1352458506ms1241oa.
The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation 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-I 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 non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I 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-I 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-I 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-I 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-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.
本研究的目的是进一步深入了解经典可溶性HLA - A、B和C类Ia（sHLA - I）以及非经典可溶性HLA - G类Ib（sHLA - G）分子在多发性硬化症（MS）免疫调节异常中所起的有效作用。我们采用酶联免疫吸附测定（ELISA）技术，对69例复发缓解型（RR）、21例继发进展型（SP）和13例原发进展型（PP）MS患者的鞘内合成以及脑脊液（CSF）和血清中的sHLA - I和sHLA - G水平进行了评估，这些患者根据疾病活动的临床和磁共振成像（MRI）证据进行了分层。我们还测试了91例患有其他炎性神经系统疾病（OIND）的患者和92例患有非炎性神经系统疾病（NIND）的患者作为神经学对照。82名健康志愿者作为sHLA - I和sHLA - G测定的进一步对照。通过特定指标检测到的MS患者鞘内sHLA - I和sHLA - G产生明显比对照组更频繁（P<0.01）。鞘内sHLA - I的合成在临床（P<0.02）和MRI活动期（P<0.001）的MS中普遍存在，而sHLA - G在脑脊液中的受限释放则在临床（P<0.01）和MRI稳定期（P<0.001）的MS中占主导。临床活动期MS患者血清中sHLA - I水平较低（P<0.001），而MRI活动期MS患者脑脊液中sHLA - I水平较高（P<0.01）。相反，临床稳定期MS患者血清中sHLA - G浓度降低（P<0.01），而MRI非活动期MS患者脑脊液中sHLA - G浓度升高（P<0.001）。在没有临床和MRI活动证据的患者中，脑脊液和血清浓度与鞘内sHLA - I和sHLA - G合成之间观察到负相关趋势，这证实了MS患者中sHLA - I和sHLA - G的鞘内产生以及脑脊液和血清浓度的波动是相互关联的。我们的结果表明，在MS中，经典sHLA - I和非经典sHLA - G产物之间可能存在一种平衡，它们以相反的方向调节MRI和临床疾病活动。
