The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs).

Immune semaphorins are a large family of proteins involved in the pathogenesis of inflammatory diseases through the regulation of immune homeostasis and tissue inflammation. We aim to assess the possible involvement of semaphorin3A (sema3A) and 4A (sema4A) in peripheral immune responses and bowel tissue inflammation of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC).Twenty-seven CD patients and 10 UC patients were studied and compared to 10 patients followed for acute diverticulitis (disease control) and 12 healthy individuals. All were evaluated for sema3A expression on T regulatory cells (Tregs), serum levels of sema3A and sema4A, and tissue expression of sema3A and sema4A in bowel biopsies.The percentage (%) of T regulatory cells (Tregs) expressing sema3A in patients with active CD (64.5% ± 14.49%) and active UC (49.8% ± 16.45%) was significantly lower when compared to that of healthy controls (88.7% ± 3.6%, p< 0.001 and p< 0.0001, respectively). This expression was seen to be in negative correlation with CD activity. Serum levels of Sema4A were significantly lower in patients with CD and UC when compared to that of controls (5.69 ± 1 .48 ng\ml for CD, 5.26 ± 1.23 ng/ml for UC patients vs 9.74 ± 2.73 ng/ml for normal controls, P<0.001). Sema4A was highly expressed in lymphocytes of the lamina propria of CD and UC patients but absent in patients with diverticulitis or in normal individuals.Altered % of Tregs expressing sema3A in patients with inflammatory bowel diseases (IBD) is partially responsible for their failure in preventing CD4+ effector T cell induced inflammation in IBD in peripheral blood. The increased expression of sema4A in bowel biopsies from CD and UC patients is suggestive of its central role in regulating local tissue inflammation in the bowel

Clinical characteristics of Crohn’s disease patients.

<p>Clinical characteristics of Crohn’s disease patients.</p

The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs) - Fig 1

<p>A: The percentage of Treg cells expressing sema3A. The percentage of Treg cells expressing sema3A in peripheral blood in patients suffering from Crohn’s disease [both active (n = 15) or in remission (n = 12)], ulcerative colitis (active, n = 10), and from patients suffering from acute diverticulitis (n = 10) compared to that from healthy controls (n = 12). Note the significantly altered percentage of Treg cells expressing sema3A in all IBD patients when compared to that of normal individuals. B: A representative figure of Treg cell expressing sema3A. A representative FACS analysis of Treg cell expressing sema3A in a CD patient compared to that of normal individual.</p

Clinical correlation.

<p>The percentage of Treg cells expressing sema3A in peripheral blood of CD patients is found to be in negative correlation with the CDAI score (r = -0.46, p = 0.016).</p

Sema3A staining in IBD.

<p>A representative biopsy from an active CD patient in which sema3A is intensely stained (+3) in the macrophages of the lamina propria (similarly in all studied groups). Black arrows denote positively stained macrophages.</p

Immunohistochemistry staining of sema4A.

<p>Sema4A is clearly detected in lymphocytes of the lamina propria in a biopsy taken from a CD patient (<b>A</b>), but was not detected in a biopsy taken from a diverticulitis patient (<b>B</b>) or from a normal individual. Black arrows denote positively stained lymphocytes.</p

Serum levels of sema4A.

<p>Serum levels of sema4A are significantly lower in CD (in active disease, n = 15) and UC patients (n = 10), when compared to the level of sema4A in normal individuals (n = 30).</p

Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis

B cell receptor (BCR) -mediated signals are enhanced when CD72 expression is deficient on B cells in autoimmune diseases. The significance of soluble CD72 (sCD72) has not been elucidated. METHODS: Soluble CD72 was analyzed in the serum of 159 SLE patients, 40 rheumatoid arthritis (RA) patients, and 100 healthy individuals. Correlations between sCD72 and SLE disease activity (SLEDAI) were assessed. RESULTS: Soluble CD72 was found increased in SLE patients, when compared to both RA patients and healthy individuals (20.2 ± 1.2 ng/ml; 10.6 ± 4.6 ng/ml and 7.2 ± 3.3 ng/ml; p < 0.001). Soluble CD72 level was significantly higher in SLE patients with renal involvement than in patients without (31.8 ± 2.3 ng/ml vs 13.9 ± 0.9 ng/ml; p < 0.001) and also with the presence of auto-antibodies. CONCLUSION: Soluble CD72 is significantly increased in SLE patients mainly in those with renal involvement. Increased sCD72 may become a potential biomarker for renal involvement in SLE