The Clinical Significance Of Soluble CD22,a B-cell Activation Marker, And The Study About Its Mechanism

Part1. The levels and clinical significances of sCD22in the serum from kidney transplant recipientsObjective: Soluble CD22(sCD22), a fragment that corresponds to the extracellular domain of CD22, has been poorly concerned in immune diseases. We hypothesize that the unmasked CD22has an increased susceptibility to the cleavage, and sCD22serves as a potential marker of B-cell activation. To determine the correlation between sCD22and graft rejection, a disease associated with B-cell activation, we attempted the detection of sCD22in the serum of kidney transplant recipients.Methods: Thirty-two serum samples from kidney transplant recipients and15healthy volunteers were collected. The study population was divided into three groups:rejection group, stable function group and control group. By enzyme-linked immunosorbent assay (ELISA), we detected the serum concentrations of sCD22.Results: We found that the levels of sCD22were elevated in recipients who were undergoing rejection comparing with recipients with stable renal functions and normal controls. A cutoff value for sCD22concentrations>2.5ng/ml showed a sensitivity of54.17%and a specificity of73.91%for identifying graft rejection from stable kidney transplant recipients.Conclusions: We showed the first detection and quantification of sCD22in kidney transplant recipients. Our study showed that sCD22serves as a potential indicator of rejection. This biomarker might be useful in early diagnosis, providing new direction for the research about rejection. Part2. The levels and clinical significances of sCD22in the serum from patients with sepsisObjective:We hypothesized that the serum concentration of sCD22correlates with the level of B-cell activation, and sCD22levels in patients with sepsis might be elevated. To assess the correlation of sCD22with sepsis, sCD22was assayed in the sera of surgical patients with sepsis.Methods:A total of104serum samples were collected, which consisted of14patients with severe sepsis,24patients with sepsis,25patients with local infection,26non-infective SIRS patients, and15healthy controls. The levels of sCD22were assayed by enzyme-linked immunosorbent assay (ELISA), and were compared with those of procalcitonin (PCT) and interleukin-6(IL-6).Results:Concentrations of sCD22levels were significantly elevated in patients with sepsis and severe sepsis, and were slightly elevated in those with non-infected SIRS or localized infection. The diagnostic effectiveness of sCD22for sepsis was as efficient as that of PCT and IL-6. In addition, the correlation of sCD22with APACHE II scores was stronger comparing to that of PCT or IL-6.Conclusions:Serum sCD22serves as a novel inflammatory mediator released during infection. This soluble biomarker displays its potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic effectiveness as efficient as that of PCT and IL-6. In addition, sCD22may predict outcomes in patients with sepsis, more efficiently than PCT and IL-6. Our present study suggested that sCD22might be potentially useful in supplementing current criteria for sepsis Part3. The experimental study about the correlation between sCD22and B-cell activationObjective: To investigate the correlation of sCD22with B-cell activation and CD22unmasking, and to determine the mechanism of sCD22production and the changes of sCD22during B-cell activation.Methods:â‘ B cells were activated by LPS or pretreated with sialidase in vitro, making the cell-surface CD22become unmasked. The level of sCD22and the expression of CD22were subsequently measured by ELISA and flow cytometry respectively.â‘¡Septic mouse models were developed by CLP or LPS peritoneal injection, and the level of sCD22and the expression of CD22were subsequently measured by ELISA and flow cytometry respectively.Results: In vitro, the sCD22levels were slightly and transiently elevated within12hours after the sialidase treatment rather than continuously increased, while LPS stimulation continuously up-regulated the levels of sCD22after24hours and approximately reached the maximum degree at72hours. For in vivo experiments, sCD22levels were continuously elevated in septic mice, with the elevation within12hours in CLP models and after12hours in LPS peritoneal injection models. Moreover, the up-regulation of CD22expression could be observed during B-cell activation, both in vitro and in vivo.Conclusions: sCD22serves as a biomarker of B-cell activation. B-cell activation leads to an up-regulated expression and the unmasking of cell-surface CD22, which results in an increased susceptibility of CD22to the cleavage and an increased production of sCD22.