The impact of multifactorial factors on the Quality of Life of Behçet's patients over 10 years.

Objective: This study analyses the 2020 survey and reviews the 2009, 2014 surveys to ascertain which Behçet's symptoms, personal and family status, patients' lifestyle, and work-related outcomes impacted on Health-Related Quality of Life (HRQoL).

Methods: Four hundred and fifty-nine Behçet's patients submitted an online survey/questionnaire. Patients provided information on socio-demographic characteristics, disease duration, historical and current symptoms, systemic and topical medication, health related lifestyle, work-related outcomes regarding employment status and claiming benefits and Quality of Life (QoL) measured by EQ-5D index.

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet's Disease.

Behçet's disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration.

Why are Behçet's disease patients always exhausted?

Objectives: Patients with Behçet's disease (BD) constantly complain of fatigue and many have problems with poor sleep. This ultimately has a major impact on all aspects of normal living. To attempt to understand this, Artificial Intelligence (AI) was used to identify potential biomarkers.

Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion.

E-cadherin mediated cell-cell adhesion plays a critical role in epithelial cell polarization and morphogenesis. Our recent studies suggest that the desmosomal cadherin, desmoglein 3 (Dsg3) cross talks with E-cadherin and regulates its adhesive function in differentiating keratinocytes. However, the underlying mechanism remains not fully elucidated.

Gamma Delta (γδ) T Cells and Their Involvement in Behçet's Disease.

Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role.

Genital ulcer severity score and genital health quality of life in Behçet's disease.

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity.

The seroprevalence and salivary shedding of herpesviruses in Behçet's syndrome and recurrent aphthous stomatitis.

Background: Behçet's syndrome (BS) is one of the multisystemic diseases that presents with oral ulceration and several other systemic manifestations including genital ulceration, folliculitis, erythema nodosum-like lesions, uveitis, and arthropathy. Ocular manifestation, central nervous system involvement, and gastrointestinal manifestation account for most of the complications of this disease, whereas orogenital ulceration and dermatological involvement affects the quality of life. The cause of the disease is not fully elucidated; however, herpesviruses have long been thought to play a pivotal role in the disease pathogenesis.

The oral mucosal and salivary microbial community of Behçet's syndrome and recurrent aphthous stomatitis.

Background: Behçet's syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS.

The role of TLR2 and 4 in Behçet's disease pathogenesis.

TLRs are PRRs that play a pivotal role in sensing exogenous pathogens and endogenous danger signals. Their role in the pathogenesis of inflammatory and immune-related diseases is gradually being unravelled. TLR2 and TLR4 are capable of sensing the oral microbial community, which is considered a potential trigger for Behçet's disease (BD).

The role of innate APOBEC3G and adaptive AID immune responses in HLA-HIV/SIV immunized SHIV infected macaques.

The AID/APOBEC family (activation induced deaminase/apolipoprotein B mRNA editing cytokine deaminase) in B cells play important roles in adaptive and innate immunity. Whereas APOBEC3G has been studied in CD4+ T cells and myeloid cells its functional potential in B cells has received little attention. AID combines two critical functions of antibodies, class switching and affinity maturation and may serve as a functional surrogate of protection.

Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian-human immunodeficiency virus infection in macaques.

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian-human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques.

Immunization with recombinant HLA classes I and II, HIV-1 gp140, and SIV p27 elicits protection against heterologous SHIV infection in rhesus macaques.

Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all linked to dextran, to investigate whether they can elicit protective immunity against heterologous simian/human immunodeficiency virus (SHIV) challenge in rhesus macaques.

A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses.

The objective of this study was to produce and evaluate the immunogenic potential of a recombinant HLA-class I antigen linked to dextran. The HLA-A*0201 heavy chain and beta2 microglobulin were cloned by PCR amplification of overlapping oligonucleotides and produced in E. coli.

Cytoskeletal proteins bound to heat-shock protein 70 may elicit resistance to simian immunodeficiency virus infection of CD4(+) T cells.

This study is based on the evidence that immunization of macaques with human CD4(+) T cells elicits prevention of simian immunodeficiency virus (SIV) infection. We hypothesized that heat-shock protein 70 (HSP70) isolated from CD4(+) T cells may act as a chaperone and carry the protective host proteins. Two moieties of HSP70 were affinity-purified from human CD4(+) T cells; an ADP preparation with HSP70-bound proteins (ADP-HSP) and an ATP control preparation.

Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.

Plasma from patients with sepsis up-regulates the expression of CD49d and CD64 on blood neutrophils.

An excessive interaction of blood neutrophils with microvascular walls may underlie the organ failure of sepsis. In this study, flow cytometric analysis was used to investigate whether plasma from 22 patients with sepsis altered the expression of the adhesion molecules (CD11a, CD11b, CD49d, and CD62L) on normal blood neutrophils and enhanced their binding to cultured endothelium. Most of the plasma samples from patients with sepsis increased the percentage of neutrophils bearing CD49d (86% samples versus 22% normal plasma samples; P < 0.

Combining human antisera to human leukocyte antigens, HIVgp120 and 70 kDa heat shock protein results in broadly neutralizing activity to HIV-1.

Objective: To elicit broadly neutralizing antibody activity by combining polyclonal human serum IgG antibodies with HIVgp120, human leukocyte antigen (HLA) class I or class II and 70 kDa heat shock protein.

Design: : In addition to HIV antigens, HIV-1 virions express HLA class I, HLA class II and 70 kDa heat shock protein molecules, which have quantitative and functional significance. The complementary effect of combining human polyclonal IgG antibodies with these antigens may result in effective broad spectrum neutralizing activity.

Stimulation of cell surface CCR5 and CD40 molecules by their ligands or by HSP70 up-regulates APOBEC3G expression in CD4(+) T cells and dendritic cells.

Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like-3G (A3G) is an intracellular innate antiviral factor that deaminates retroviral cytidine to uridine. In an attempt to harness the anti-HIV effect of A3G, we searched for an agent that would up-regulate A3G and identify the receptors involved. Stimulation of cell surface CCR5 with CCL3 and CD40 with CD40L or both molecules with microbial 70-kDa heat shock protein (HSP)70 up-regulated A3G mRNA and protein expression in human CD4(+) T cells and monocyte-derived dendritic cells (DC), demonstrated by real-time PCR and Western blots, respectively.

Interaction between the CCR5 chemokine receptors and microbial HSP70.

Evidence is presented that the microbial 70-kD heat shock protein (HSP70) binds to CCR5 chemokine receptors in CCR5-transfected cell lines and in primary human cells. Significant CCR5-mediated calcium mobilization was stimulated by HSP70 and inhibited with TAK 779, which is a specific CCR5 antagonist. HSP70-mediated activation of the p38 MAPK phosphorylation signaling pathway was also demonstrated in CCR5-transfected HEK 293 cells.

Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity.

The hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. Rectal or vaginal mucosal administration of 10(4)-10(7) unmatched mononuclear cells induced significant dose-dependent T-cell proliferation stimulated by the allogeneic cells in rhesus macaques. This was associated with a significant upregulation of CD8(+) T-cell-derived suppressor factor, as well as the CC chemokines CCL3, CCL4 and CCL5.

Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells.

The 70-kDa microbial heat shock protein (mHSP70) has a profound effect on the immune system, interacting with the CD40 receptor on DC and monocytes to produce cytokines and chemokines. The mHSP70 also induces maturation of dendritic cells (DC) and thus acts as an alternative ligand to CD40L on T cells. In this investigation, we have identified a cytokine-stimulating epitope (peptide 407-426), by activating DC with overlapping synthetic peptides (20-mers) derived from the sequence of mHSP70.

A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection.

Objective: To develop a novel SIV-CCR5 receptor vaccine strategy that will protect macaques from SHIV infection by the vaginal mucosal route.

Design: The rationale for this strategy is that humans who express the homozygous delta32 CCR5 mutation and the associated upregulation of CC chemokines, the down-modulation of cell-surface expression of CCR5 and antibodies to CCR5 are protected against HIV infection.

Methods: A vaccine was prepared consisting of three extracellular peptides of CCR5, an N-terminal HIV gp120 fragment generated in transgenic plants and recombinant SIV p27.

Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic cells, and adjuvant function by the peptide binding fragment of heat shock protein 70.

The peptide binding C-terminal portion of heat shock protein (HSP)70 (aa 359-610) stimulates human monocytes to produce IL-12, TNF-alpha, NO, and C-C chemokines. The N-terminal, ATPase portion (HSP70(1-358)) failed to stimulate any of these cytokines or chemokines. Both native and the truncated HSP70(359-610) stimulation of chemokine production is mediated by the CD40 costimulatory molecule.