Low Urine Secretion of Semaphorin3A in Lupus Patients with Proteinuria.

Immune semaphorins are important in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to correlate with SLE disease activity. The aim was to assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Urine levels of sema3A were analyzed in 38 SLE patients, 13 with renal involvement, and were compared to 10 healthy volunteers and 8 RA patients (disease control group). The excretion of urine sema3A was found to be significantly lower in SLE patients compared to healthy volunteers and RA patients (4.9 ± 3.9 ng/ml, 8.5 ± 2.7 ng/ml, 9.85 ± 1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was significantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0 ± 3.4 ng/ml vs. 6.5 ± 3.8 ng/ml, p = 0.03). Urine sema3A inversely correlated with proteinuria and SLE disease activity. Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.

The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A.

Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target.

The role of vascular endothelial growth factor in Langerhans cell histiocytosis.

In angiogenesis, new blood vessels are generated from pre-existing ones. It plays a major role in tumor growth and metastasis. The main pro-angiogenic factor is the vascular endothelial growth factor (VEGF). VEGF displays high specificity for vascular endothelial cells and also elicits a pronounced angiogenic response in a variety of in vivo models. VEGF withdrawal has been shown to result in regression of vasculature in tumors. The pathogenic and the angiogenic processes of Langerhans cell histiocytosis (LCH) are not yet clear. The purpose of this study was to investigate the extent of the angiogenic response in LCH tumors. The authors examined tissue sections from LCH patients with single lesion (5 patients) or multisystem disease (5 patients). The preparations were examined by using monoclonal anti-VEGF antibody, CD34, and factor VIII-like antigen. VEGF was expressed in 70% of the cases examined. All the multisystem lesions were positive, as were two of the five single-lesion tumors. LCH cells expressed VEGF. The blood vessel density was significantly higher within the lesion than in normal margins. The findings that VEGF was expressed in LCH cells and that all multisystem lesions were VEGF producers raise the possibility of using anti-angiogenic drugs to treat these patients. Further studies to explore the role of angiogenesis in LCH are warranted.