Timing of Serum Soluble HLA-G Levels in Acute and Subacute Phases After Spontaneous Intracerebral Hemorrhage

Abstract

Serum levels of sHLA-G (sHLA-G1/HLA-G5) antigens and their soluble isoforms, sHLA-G1 and HLA-G5, were measured by ELISA in 22 patients with spontaneous intracerebral hemorrhage (SICH) at 24 h, 48 h and 7 days after bleeding. The perihematomal edema volume was calculated on non-enhanced computed tomography scans using the formula AxBxC/2 at the same time points. The mean serum concentrations of sHLA-G1/HLA-G5 and sHLA-G1 as well as the perihematomal edema volume changed significantly over time (p < 0.0001, p < 0.001 and p < 0.0001, respectively), whereas no statistical differences were found in serum HLA-G5 concentrations over the course of the experiment. In comparison to the values found at 24 h, sHLA-G1/HLA-G5 and sHLA-G1 increased at 48 h and then decreased at 7 days, whereas the perihematomal edema volume was more elevated at 48 h and, to a lesser extent, at 7 days. A positive correlation was detected between mean serum sHLA-G1/HLA-G5 and sHLA-G1 levels and perihematomal edema volume at 24 h (p < 0.02) and at 48 h (p < 0.01). Our results may indicate a role for sHLA-G in inflammatory mechanisms related to SICH, where these proteins probably act as anti-inflammatory molecules and are predominantly produced as the sHLA-G1 isoform.

HLA-G: a look back, a look forward

“…The involvement of HLA-G in inflammatory diseases was noted in 2001 in the contexts of psoriasis [14] and atopic dermatitis [15]. Since then, HLA-G has been repeatedly associated with inflammatory pathologies, including multiple sclerosis in 2003 [16], Crohn's disease in 2004 [17], asthma in 2005 [18], rheumatoid arthritis and celiac disease in 2006 [19,20]…through to spontaneous intracerebral hemorrhage in 2010 [21]. Yet, the possible role of HLA-G in inflammation as an immune process is seldom remembered.…”

Serum biomarkers of spontaneous intracerebral hemorrhage induced secondary brain injury

“…Serum levels of both in conjunction and HLA-G1 alone have been shown to correlate with hematoma and edema volumes at 24 and 48 h from onset of SICH [118,119]. HLA-G levels at 7 days post-ictus were significantly reduced compared to values at 24 h [118,119]. These findings hint at possible time-dependent roles of HLA-G, particularly the HLA-G1 isoform, in hematoma and edema growth dynamics.…”

“…HLA-G1 and HLA-G5 are regarded as the most functionally important isoforms of HLA-G [118,119]. Serum levels of both in conjunction and HLA-G1 alone have been shown to correlate with hematoma and edema volumes at 24 and 48 h from onset of SICH [118,119].…”

“…Human Leukocyte Antigen-G (HLA-G) molecules are regulatory factors that may attenuate inflammatory processes in the CNS [118,119]. HLA-G1 and HLA-G5 are regarded as the most functionally important isoforms of HLA-G [118,119].…”

Emerging topics and new perspectives on HLA-G

“…In this setting, it is commonly presumed that a strong inflammatory response could contribute to secondary injury promoted by edema reaction that develops in the region peripheral to hematoma [47]. A recent study [48] reported, for the first time, that serum sHLA-G and sHLA-G1 levels showed a characteristic time course after hematoma appearance, since they increased at 48 h and then decreased at 7 days when compared to corresponding baseline values observed at 24 h after bleeding. Conversely, no significant changes in serum concentrations of HLA-G5 were found over time after SICH.…”