Protein S Deficiency and Antibodies to Protein S in Patients With Behcet's Disease

Guermazi, Sami; Hamza, M; Dellagi, Koussay

doi:10.1016/s0049-3848(97)00063-7

Cited by 40 publications

(21 citation statements)

References 19 publications

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“…7 24 Although the prevalence of deep venous thrombosis is not higher in ocular than in non-ocular patients, venous occlusions are more common than arterial thrombus and protein S deficiency has been suggested as the pathogenesis for thrombogenesis. 25 Although many hypotheses have been suggested as the cause of obliterative retinal vasculitis and thrombosis, the exact aetiology is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet's disease

2002

British Journal of Ophthalmology

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Background/aims: Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BD has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BD and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity. Methods: 43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BD. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hyperhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including α 1 antitrypsin, α 2 macroglobulin, erythrocyte sedimentation rate, and neutrophil count. Results: The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15.83 (4.44) v 7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) µmol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) µmol/l, p <0.001). Serum tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BD, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls. Conclusions: Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease.

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Section: Discussionmentioning

confidence: 99%

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet's disease

2002

British Journal of Ophthalmology

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“…Aberrant expression of TAM members also has been reported in autoimmune disorders. For instance, reduced expression of TAM receptors in circulating immune cells as well as low plasma concentrations of TAM ligands are evident in lupus, Behcet’s disease, rheumatoid arthritis, inflammatory bowel disease, and psoriasis patients [58,99,100,101,102,103]. Interestingly, elevated concentrations of circulating soluble TAM receptors have also been detected in patients with lupus, Sjogren’s syndrome, rheumatoid arthritis, and Behcet’s disease [95,104,105,106,107], which suggest that TAM receptor shedding could have an important role in the pathogenesis of autoimmunity.…”

Section: Tam Signaling In Autoimmunitymentioning

confidence: 99%

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

Paolino

Penninger

2016

Cancers

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The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

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“…Changes in the plasma concentration of Axl/Gas6 have been reported in rheumatic diseases such as SLE48, BD4647 and RA49. Significantly increased Axl levels were also observed in patients with BD47.…”

Section: Discussionmentioning

confidence: 85%

Analysis of receptor tyrosine kinase genetics identifies two novel risk loci in GAS6 and PROS1 in Behçet’s disease

Qin

Lin

Zhang

et al. 2016

Sci Rep

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The TAM kinase (Tyro3, Axl, Mer) and its two ligands (Gas6 and protein S) have been shown to play an important regulatory role in the innate immune response. The present study aimed to investigate whether the tag single-nucleotide polymorphisms (tag SNPs) of these 5 protein-coding genes are associated with Behçet’s disease (BD). A two-stage association study was performed in a total of 907 BD patients and 1780 healthy controls. Altogether 32 polymorphisms were tested, using a Sequenom MassARRAY genotyping method in the first stage and a PCR-restriction fragment length polymorphism (PCR-RFLP) assay in the replication phase. Real-time PCR was performed to test the relative mRNA expression level of GAS6 and PROS1 from different SNP genotyped healthy individuals. The frequency of the C allele and CC genotype of rs9577873 in GAS6 (Pc = 4.92 × 10−5, Pc = 1.91 × 10−5, respectively) and A allele and AA genotype of rs4857037 in PROS1 (Pc = 1.85 × 10−6, Pc = 4.52 × 10−7, respectively) were significantly increased in BD. GAS6 expression in CC carriers of rs9577873 was significantly lower than that in CT/TT individuals (P = 0.001). Decreased expression of GAS6 and increased pro-inflammatory cytokines (IL-6 and IFN-γ: P = 4.23 × 10−4, P = 0.011, respectively) in individuals carrying the CC genotype suggest that the TAM-GAS6/PROS1 signal pathway may be involved in the pathogenesis of BD.

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Protein S Deficiency and Antibodies to Protein S in Patients With Behcet's Disease

Cited by 40 publications

References 19 publications

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet's disease

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet's disease

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

Analysis of receptor tyrosine kinase genetics identifies two novel risk loci in GAS6 and PROS1 in Behçet’s disease

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