Putative loss of CD83 immunosuppressive activity in long-standing complication-free juvenile diabetic patients during disease progression

Abstract

The CD83 molecule is a known marker of dendritic cell differentiation process, and its soluble form (sCD83) exerts immunosuppressive functions. In our research, we examined whether the sCD83 plasma concentration is impaired in DM1 children and if the expected changes are in line with the disturbed process of monocyte's transformation into mCD83 + monocyte-derived cells. 28 newly diagnosed (ND-DM1) and 30 long-standing (LS-DM1) patients were enrolled into our study. We revealed that the examined cells show a high mCD83 expression level in ND-DM1, which was significantly downregulated by the TNF-α stimulation. The results were in line with those from healthy controls. We also observed that monocyte differentiation process into CD83 + cells was much defective in LS-DM1 children and the mCD83 expression level seems not to be controlled by TNF-α. Moreover, the sCD83 level was significantly decreased in plasma from LS-DM1 children and it was negatively related to HbA1c levels, while no correlations were observed between TNF-α plasma concentration or disease duration. Summarizing, our results suggest that reduced sCD83 levels may correspond with a poor metabolic control in LS-DM1 patients and therapeutic administration of this molecule may indicate a new therapy approach in the chronic phase of diabetes.

The CD83 Molecule – An Important Immune Checkpoint

“…Recently, Juhas et al showed that decreased sCD83 plasma concentrations significantly correlated with disease progression in long-standing complication-free juvenile diabetic patients (110). Loss of sCD83 levels in the plasma of these patients coincided with increased HbA1c levels, a factor associated with disease progression.…”

“…Understanding the effects of specific immune modulating interventions can elucidate definitive molecular or cellular checkpoints of the complex inflammatory networks which modulate autoimmune diseases. Given the important role of CD83 for immune responses to non-self, it is not surprising that there are several reports of CD83 being involved in autoimmune processes (38,39,55,(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110). A recent report summarized immune-modulating functions of sCD83 therapy in models of multiple sclerosis, autoimmune uveitis and systemic lupus erythematosus (3).…”

Evaluation of Soluble CD90: Potential for Diagnostic Significance in Endometriosis Patients

“…The soluble form of CD83 (sCD83) has an inhibitory effect on T-cell activation and maturation of dendritic cells [ 34 , 35 ]. At background level, sCD83 [ 36 ] is found in serum and plasma from healthy people and in modified concentrations in patients with hematological malignancies [ 37 ], rheumatoid arthritis [ 38 ], and juvenile diabetes [ 39 ]. Various tumor cell types induce immune suppression via sCD83 release and evade immune surveillance [ 40 , 41 ].…”