Anti-VCAM1 monoclonal antibody, clone 693DU36.7.5

The genes associated with Sjogren syndrome (SS) can be assigned to the NF-kappa B pathway, the IFN signaling pathway, lymphocyte signaling, and antigen presentation. The frequencies of risk variants show they are common with modest genetic effects. The strongest genetic association outside the human leukocyte antigen region is in IRF5, a gene relevant in the IFN signaling pathway and for B cell differentiation. Although no association has been found with the NF-kappa B gene itself, associations in TNFAIP3 and TNIP1 (both genome-wide significant), VCAM1 and IRAK1 BP (both suggestive), point to genetic explanations for dysregulation of the NF-kappa B pathway in SS.

Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI). However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (n = 21), patients with recent lacunar infarcts (LI, n = 28) and healthy controls (n = 31), consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1), growth factors (SCF, SCGFb, HGF, IL3), immunoglobulin-type adhesion molecules (ICAM1, VCAM1), proinflammatory cytokines (IL18, INFa2, MIF, IL12p40), cell surface receptors on T-cells (IL2Ra), and inductors of apoptosis (TRAIL) was assessed in plasma samples by Luminex xMAP (TM) technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC) analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI >= LI > Ctrl). A different trend was observed for IL16 (SBI < LI > Ctrl), SCF (LI < SBI > Ctrl) and SCGFb (SBI > LI < Ctrl). SBI subjects had significantly increased levels of MIG when compared to controls (LI <= SBI > Ctrl) and IL18 when compared to LI patients (Ctrl <= SBI > LI). All the other immunological markers did not significantly differ among groups. According to ROC analysis, the best predictor for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity 77%), while SCF had the best performance in distinguishing LI patients (AUC = 0.84, sensitivity 86%, specificity 68%). These results confirm the involvement of inflammatory processes in cerebrovascular disorders, particularly in SBI, a very common age-related condition. The differences in plasma profile of inflammatory molecules may underlie different pathological mechanisms in SBI and LI patients.