Semaphorin 3A, a potential immune regulator in familial Mediterranean fever.

OBJECTIVES: Semaphorin 3A (sema3A) plays a regulatory role in immune responses with effects on both T and B regulatory cells. Familial Mediterranean fever (FMF) is an autoinflammatory disease, yet a possible role for regulatory T and B cells has been described. METHODS: 17 FMF patients during attack and then in remission, 8 FMF patients with smoldering disease and 12 healthy controls were enrolled. Sema3A in serum and its expression on regulatory T and B cells was evaluated. Clinical parameters of FMF patients were assessed. RESULTS: Semaphorin 3A serum level was lower in FMF patients during attack, smoldering disease or remission than healthy controls, (242.3±9.8 ng/ ml vs. 258.9±11.5 ng/ml vs. 232.5±22.7 ng/ml vs. 323.3±160.2 ng/ml, respectively p<0.05). This decrease was specifically noted on regulatory B and T cells in FMF patients during attack and in smoldering disease and normalized in remission. CONCLUSIONS: Sema3A expression on T and B regulatory lymphocytes is low in FMF patients during attack and in smoldering disease compared to the expression in remission and healthy controls. These results are in line with previous descriptions suggesting a possible role of regulatory T cells in termination of FMF attacks. Further studies are needed to verify these preliminary findings.

Semaphorin 3A: an immunoregulator in systemic sclerosis.

ABSTARCT: Semaphorin 3A (sema3A) plays a regulatory role in immune responses, mainly affecting the activation of regulatory T cells. It has been found to correlate with disease activity in rheumatoid arthritis and systemic lupus erythematosus (SLE). To investigate the expression of sema3A in patients with systemic sclerosis (SSc) compared to healthy controls and SLE disease controls and to correlate it with clinical characteristics, 27 SSc patients, 42 SLE patients and 28 healthy controls were enrolled. Serum level of sema3A was measured by ELISA, and expression of sema3A on regulatory T cells was evaluated by FACS analysis. SSc patients were evaluated for demographics, clinical manifestations, routine laboratory results, nailfold videocapillaroscopy, pulmonary function tests, echocardiograms, modified Rodnan skin score, and disease activity and severity scores. Serum levels of semaphorin 3A were lower in SSc compared to healthy controls 14.38 ± 5.7 versus 27.14 ± 8.4 ng/ml, p < 0.0001 and similar to SLE 15.7 ± 4.3 ng/ml. The expression of semaphorin 3A on regulatory T cells was also lower in SSc compared to healthy controls 61.7 ± 15.7 versus 88.7 ± 3. 7 % (p < 0.0001). Semaphorin 3A serum level inversely correlated with the duration of disease: r = -0.4, p = 0.036 and with low C4 level r = 0.66, p = 0.026. SCL-70 antibody positivity was associated with a lower semaphorin 3A level (difference in mean of 3.44, p = 0.06). Sema3A expression is low in SSc serum and more specifically on regulatory T cells. This may help explain the reduced activation of regulatory T cells in SSc.

Brief report: lysyl oxidase is a potential biomarker of fibrosis in systemic sclerosis.

OBJECTIVE: Fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc). Levels of lysyl oxidase (LOX), an extracellular enzyme that stabilizes collagen fibrils, have been found to be elevated in the skin of SSc patients, but have not been evaluated in the serum or correlated with the clinical parameters. We undertook this study to evaluate serum LOX levels in SSc patients and to correlate these levels with clinical parameters of SSc. METHODS: SSc patients were evaluated for demographic features, clinical manifestations, routine laboratory tests, serum autoantibodies, serum LOX concentrations, and nailfold capillaroscopy patterns. They underwent pulmonary function testing, echocardiography, and high-resolution computed tomography scans of the lung, assessment of skin fibrosis by the modified Rodnan skin thickness score (MRSS), and assessment of disease severity and activity by the Medsger severity scale and the Valentini activity index. RESULTS: Twenty-six SSc patients were evaluated and compared with 25 healthy controls and with 9 disease control patients with primary myelofibrosis. Almost 62% of the SSc patients (16 of 26) had limited cutaneous SSc (lcSSc), while 38% had diffuse cutaneous SSc (dcSSc) (10 of 26); 31% of the patients (8 of 26) had lung involvement. The LOX concentration in SSc patients was higher than that in healthy controls and similar to that in disease controls (P < 0.0001), and it was significantly higher in patients with dcSSc than in those with lcSSc (P = 0.006). The LOX concentration correlated with the MRSS in patients without lung fibrosis. CONCLUSION: This study is the first to demonstrate high serum LOX levels in SSc patients that correlate specifically with skin fibrosis. These correlations suggest that LOX levels may serve as a novel biomarker of fibrosis. Future studies are warranted to determine whether LOX is a potential therapeutic target in SSc.

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant.

INTRODUCTION: To investigate whether immunologic factors in breast milk change in response to nursing infants' infection. RESULTS: Total CD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. Such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. Secretory immunoglobulin A levels did not change significantly in the study or control group. DISCUSSION: During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants. METHODS: Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.