Soft Tissue Substitutes in Periodontal and Peri-Implant Soft Tissue Augmentation: A Systematic Review.

BACKGROUND: Different extracellular matrix (ECM)-based technologies in periodontal and peri-implant soft tissue augmentation have been proposed in the market. The present review compared the efficacy of soft tissue substitutes (STSs) and autogenous free gingival grafts (FGGs) or connective tissue grafts (CTGs) in mucogingival procedures to increase keratinized tissue (KT) width around teeth and implants. METHODS: Two independent examiners performed an electronic search on MEDLINE and the Cochrane Library based on the following PICOS format: (P) adult patients; (I) soft tissue substitutes and FGGs/CTGs; (C) STSs vs. CTGs; STSs vs. FGGs; STSs vs control; (O) KT width gain; (S) systematic reviews, randomized controlled trials. Studies published before November 2023 were included. RESULTS: Around teeth, all biomaterials showed superior performance compared to a coronally advanced flap (CAF) alone for treating gingival recessions. However, when compared to CTGs, acellular dermal matrices (ADMs) yield the most similar outcomes to the gold standard (CTGs), even though in multiple recessions, CTGs continue to be considered the most favorable approach. The use of STSs (acellular matrix or tissue-engineered) in combination with apically positioned flaps (APF) resulted in significantly less gain in KT width compared to that achieved with FGGs and APFs. Around dental implants, free gingival grafts were deemed more effective than soft tissue substitutes in enhancing keratinized mucosa width. CONCLUSIONS: Based on the available evidence, questions remain about the alternative use of soft tissue substitutes for conventional grafting procedures using free gingival grafts or connective tissue grafts around teeth and implants.

Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet's Syndrome and Psoriatic Arthritis.

Behçet's syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α-a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases-to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.

Skin IL-17A and IFN-γ Production Correlate with Disease Severity in Patients with Psoriasis and Streptococcal Infection.

Psoriasis is a multisystemic inflammatory disorder mainly involving the skin and joints, whose etiopathogenesis is still not completely understood. An association with streptococcal throat infection has been suggested. We aim to investigate a correlation between IL-17A and IFN-γ production by T cells infiltrating skin lesions and PASI in 313 patients with psoriasis, compared with that in 252 healthy controls. The phenotype of ß-hemolytic Streptococci-specific infiltrating T cells in skin lesions was evaluated and characterized for IFN-γ, IL-4, and IL-17A production. In addition, PBMCs were tested by ELISpot for IFN-γ and IL-17A after streptococcal antigen exposure. A total of 64 of 313 (20.4%) patients with psoriasis had throat streptococcal infection. Of the 3,868 skin-derived T-cell clones from psoriasis with streptococcal infection, 66% proliferated in response to ß-hemolytic Streptococci antigens. Most ß-hemolytic Streptococci-specific T cells displayed T helper 17 and T helper 1 phenotypes. The levels of IFN-γ and IL-17A secreted by skin-infiltrating T cells of patients with psoriasis significantly correlated with PASI score. In ß-hemolytic Streptococci-positive patients, IFN-γ and IL-17A production by peripheral blood T cells after stimulation with streptococcal antigens was quantified by ELISpot. The results obtained may suggest ELISpot as a useful diagnostic tool to identify patients with psoriasis that may deserve antibiotic treatment.

The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma.

BACKGROUND: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. METHODS: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori-infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. RESULTS: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. CONCLUSION: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

Decline in Total Serum IgE and Soluble CD30 in the Context of Soil-Transmitted Helminth Decline in Bolivia.

In the Bolivian Chaco, recent surveys documented a dramatic decrease in the prevalence of soil-transmitted helminth (STH) infections as compared with the 1980s after thirty years of preventive chemotherapy (PC). Concomitant immunological rearrangements are expected. Because nematode infections are associated with increased levels of circulating IgE and glycoprotein CD30 soluble form (sCD30), this study aims to evaluate changes in serological markers of T helper (Th)2-cells activity between 1987 (high STH prevalence) and 2013 (low STH prevalence) in rural communities in the Bolivian Chaco area. We collected 151 sera during two different surveys in 1987 (n = 65) and 2013 (n = 86) and measured the concentration of total IgE and sCD30 by immunoassays. We found a statistically significant age-independent decrease in the total IgE (P < 0.0001) and sCD30 (P < 0.0001) from 1987 to 2013. The significant decrease in serological Th2 markers (IgE and sCD30) between 1987 and 2013 is consistent with the drop in STH prevalence in this geographical area during the same period of time. Further studies might elucidate the clinical and epidemiological impact of these serological rearrangements.

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.

STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.

LIOFeron®TB/LTBI: A novel and reliable test for LTBI and tuberculosis.

OBJECTIVES: High accuracy diagnostic screening tests for tuberculosis (TB) are required to improve the diagnosis of both active TB and latent Mycobacterium tuberculosis (MTB) infection (LTBI). The novel IGRA LIOFeron®TB/LTBI assay was tested and its accuracy was compared to the QuantiFERON®-TB Gold Plus assay. METHODS: A total of 389 subjects were enrolled in two cohorts and classified as healthy, active TB or LTBI persons. The blood of all the patients was tested with LIOFeron®TB/LTBI assay, containing MTB alanine dehydrogenase, able to differentiate active TB from LTBI diagnosis. The results obtained with both IGRAs, performed on the same 250 samples, were finally compared. RESULTS: The two assays demonstrated an excellent concordance of their results with patients' diagnosis of MTB infection. ROC analysis for QuantiFERON®-TB Gold Plus showed sensitivity and specificity respectively of 98% and 97% in diagnosing active TB patients and 85% and 94% in diagnosing LTBI subjects. LIOFeron®TB/LTBI assay showed sensitivity and specificity respectively of 90% and 98% in diagnosing active TB patients and 94% and 97% in diagnosing LTBI subjects. CONCLUSIONS: The two IGRAs displayed the same high accuracy in diagnosing MTB infection/TB disease, and LIOFeron®TB/LTBI assay demonstrated higher sensitivity than QuantiFERON®-TB Gold Plus test in LTBI detection.

Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia.

The intrinsic factor is the major humoral autoantigen in pernicious anemia/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-α, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Interleukin-17/Interleukin-21 and Interferon-γ producing T cells specific for ß2 Glycoprotein I in atherosclerosis inflammation of systemic lupus erythematosus patients with antiphospholipid syndrome.

Systemic lupus erythematosus is frequently associated with antiphospholipid syndrome. Patients with lupus-antiphospholipid syndrome are characterized by recurrent arterial/venous thrombosis, miscarriages, and persistent presence of autoantibodies against phospholipid-binding proteins, such as ß2-Glycoprotein I. We investigated the cytokine production induced by ß2-Glycoprotein I in activated T cells that infiltrate in vivo atherosclerotic lesions of lupus-antiphospholipid syndrome patients. We examined the helper function of ß2-Glycoprotein I-specific T cells for tissue factor production, as well as their cytolytic potential and their helper function for antibody production. Lupus-antiphospholipid syndrome patients harbor in vivo activated CD4+ T cells that recognize ß2-Glycoprotein I in atherosclerotic lesions. ß2-Glycoprotein I induces T-cell proliferation and expression of both Interleukin-17/Interleukin-21 and Interferon-γ in plaque-derived T-cell clones. ß2-Glycoprotein I-specific T cells display strong help for monocyte tissue factor production, and promote antibody production in autologous B cells. Moreover, plaque-derived ß2-Glycoprotein I-specific CD4+ T lymphocytes express both perforin-mediated and Fas/FasLigand-mediated-cytotoxicity. Altogether, our results indicate that ß2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

Role of Mycobacterium avium lysate INF-γ, IL-17, and IL-2 ELISPOT assays in diagnosing nontuberculous mycobacteria lymphadenitis in children.

Nontuberculous mycobacteria are the most frequent cause of chronic cervical lymphadenitis in childhood. The aim of the study was to evaluate the performance of IL-2, IL-17, and INF-γ in-house enzyme-linked immunospot assays using a Mycobacterium avium lysate, in order to identify a noninvasive diagnostic method of nontuberculous mycobacteria infection. Children with subacute and chronic lymphadenopathies or with a previous diagnosis of nontuberculous mycobacteria lymphadenitis were prospectively enrolled in the study. Sixty children with lymphadenitis were included in our study: 16 with confirmed infection (group 1), 30 probable infected (group 2) and 14 uninfected (group 3). Significantly higher median cytokine values were found in group 1 vs group 2, in group 1 vs group 3, and in group 2 vs group 3 considering IL-2-based enzyme-linked immunospot assay (p = 0.015, p < 0.001, p = 0.004, respectively). INF-γ-based enzyme-linked immunospot assay results were significantly higher in group 2 vs group 3 (p = 0.010). Differences between infected and uninfected children were not significant considering IL-17 assays (p = 0.431). Mycobacterium avium lysate IL-2 and INF-γ-based enzyme-linked immunospot assays seem to be promising noninvasive diagnostic techniques for discriminating children with nontuberculous mycobacteria lymphadenitis and noninfected subjects.

CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface.

CD25 deficiency is a very rare autosomal recessive disorder that shows a clinical phenotype highly overlapping IPEX syndrome with an increased susceptibility to viral, bacterial, and fungal infections. It is due to mutations in the IL2Rα gene that codes for the α subunit of the IL2 receptor complex. Here we report the characterization of a novel IL2Rα gene mutation leading to a severe protein conformational alteration that abrogates its cell surface expression in a child presenting with early-onset IPEX-like disorder. Cytofluorimetric analysis revealed the total absence of CD25 cell surface expression and addressed IL2Rα molecular investigation. The early clinical and molecular diagnosis of CD25 deficiency in this patient promptly led to hematopoietic stem cell transplantation (HSCT), allowing complete resolution of the symptoms and definitive cure of the disease.

The lipoprotein HP1454 of Helicobacter pylori regulates T-cell response by shaping T-cell receptor signalling.

Helicobacter pylori (HP) is a Gram-negative bacterium that chronically infects the stomach of more than 50% of human population and represents a major cause of gastric cancer, gastric lymphoma, gastric autoimmunity, and peptic ulcer. It still remains to be elucidated, which HP virulence factors are important in the development of gastric disorders. Here, we analysed the role of the HP protein HP1454 in the host-pathogen interaction. We found that a significant proportion of T cells isolated from HP patients with chronic gastritis and gastric adenocarcinoma proliferated in response to HP1454. Moreover, we demonstrated in vivo that HP1454 protein drives Th1/Th17 inflammatory responses. We further analysed the in vitro response of human T cells exposed either to an HP wild-type strain or to a strain with a deletion of the hp1454 gene, and we revealed that HP1454 triggers the T-cell antigen receptor-dependent signalling and lymphocyte proliferation, as well as the CXCL12-dependent cell adhesion and migration. Our study findings prove that HP1454 is a crucial bacterial factor that exerts its proinflammatory activity by directly modulating the T-cell response. The relevance of these results can be appreciated by considering that compelling evidence suggest that chronic gastric inflammation, a condition that paves the way to HP-associated diseases, is dependent on T cells.

Novel M. tuberculosis specific IL-2 ELISpot assay discriminates adult patients with active or latent tuberculosis.

BACKGROUND: Tuberculosis (TB) still is a major worldwide health problem, with 10.4 million new cases in 2016. Only 5-15% of people infected with M. tuberculosis develop TB disease while others remain latently infected (LTBI) during their lifetime. Thus, the absence of tests able to distinguish between latent infection and active tuberculosis is one of the major limits of currently available diagnostic tools. METHODS: A total of 215 patients were included in the study as active TB cases (n = 73), LTBI subjects (n = 88) and healthy persons (n = 54). Peripheral blood mononuclear cells (PBMCs) were isolated from each patient and the LIOSpot® TB anti-human IL-2 ELISpot assay was performed to test their proliferative response to M. tuberculosis antigens ESAT-6, CFP-10 and Ala-DH. Statistical analysis was performed to define the sensitivity and the specificity of the LIOSpot® TB kit for each antigen used and to set the best cut off value that enables discrimination between subjects with active TB or latent TB infection. RESULTS: Comparing the LIOSpot® TB results for each tested antigen between uninfected and infected subjects and between people with latent infection and active TB disease, the differences were significant for each antigen (p< 0.0001) but the ROC analysis demonstrated a high accuracy for the Ala-DH test only, with a cut off value of 12.5 SFC per million PBMCs and the Ala-DH ROC curve conferred a 96% sensitivity and 100% specificity to the test. For the ESAT-6 antigen, with a best cut off value of 71.25 SFC per million PBMCs, a sensitivity of 86% and specificity of 36% was obtained. Finally, the best cut off value for CFP-10 was 231.25 SFC per million PBMCs, with a sensitivity of 80% and a specificity of 54%. Thus, as for IGRA assays such as Quantiferon and T-Spot TB tests, ESAT-6 and CFP-10 are unable to distinguish LTBI from active TB when IL-2 is measured. On the contrary, the IL-2 production induced by Ala-DH, measured by LIOSpot® TB kit, shows high sensitivity and specificity for active TB disease. CONCLUSIONS: This study demonstrates that the LIOSpot® TB test is a highly useful diagnostic tool to discriminate between latent TB infection and active tuberculosis in adults patients.

ß2 Glycoprotein I Recognition Drives Th1 Inflammation in Atherosclerotic Plaques of Patients with Primary Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent arterial/venous thrombosis and miscarriages in the persistent presence of autoantibodies against phospholipid-binding proteins (aPLs), such as ß2 glycoprotein I (ß2GPI). In addition to the aPL thrombophilic effect, arterial thrombosis was related to accelerated atherosclerosis in animal models; however, contrasting findings were reported in primary APS patients with regard to the increased number of plaques or abnormal arterial wall thickness. We investigated the cytokine production induced by ß2GPI in activated T cells that infiltrate in vivo atherosclerotic lesions of primary APS patients with atherothrombosis. We also examined the helper function of ß2GPI-specific T cells for monocyte matrix metalloproteinase-9 and tissue factor production, as well as their cytolytic potential and their helper function for Ab production. APS patients with atherothrombosis harbor in vivo-activated CD4+ T cells that recognize ß2GPI in atherothrombotic lesions. ß2GPI induces T cell proliferation and IFN-γ expression in plaque-derived T cell clones. ß2GPI-specific T cells display helper function for monocyte matrix metalloproteinase-9 and tissue factor production and promote Ig production in autologous B cells. Moreover, plaque-derived ß2GPI-specific CD4+ T lymphocytes express perforin-mediated and Fas/Fas ligand-mediated cytotoxicity. ß2GPI, and especially the DI domain, drive a local Th1 inflammatory response, with subsequent plaque instability that eventually favors atherothrombosis. This finding may explain the association between aPLs and arterial thrombosis, despite the lack of evidence of surrogate markers for atherosclerosis in primary APS.

Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease.

BACKGROUND: Gastrointestinal involvement is one of the most serious in Behçet disease, potentially leading to severe complications. Aim of this study was to investigate at mucosal level the T-cell responses in Behçet patients with early intestinal involvement. METHODS: We isolated T cells from intestinal mucosa of 8 patients with intestinal symptoms started within 6 months. T lymphocytes were cloned and analyzed for surface phenotype and cytokines production. RESULTS: We obtained 382 T-cell clones: 324 were CD4+ and 58 were CD8+. Within the 324 CD4+ clones, 195 were able to secrete IFN-γ and TNF-α, but not IL-4, nor IL-17 thus showing a polarized Th1 profile, whereas CD4 clones producing both IFN-γ and IL-17 (Th1/Th17 profile) were 79. Likewise, the number of CD8 clones producing type 1 cytokines was higher than those of CD8 clones producing both type 1 and 2 cytokines.Almost all intestinal-derived T-cell clones expressed perforin-mediated cytotoxicity and Fas-Fas Ligand-mediated pro-apoptotic activity. CONCLUSIONS: Our results indicate that in the early stages of the disease, both Th1 and Th17 cells drive inflammation leading to mucosal damage via abnormal and long-lasting cytokines production as well as via both perforin- and Fas-Fas ligand-mediated cytotoxicity. Finally, all the T cells at mucosal level were able to produce large amount of TNF-α, suggesting that its production is a property of intestinal T cells of patients with early active intestinal disease. These results support the therapy with anti-TNF-α agents and suggest the use of anti-IL-17 monoclonal antibodies in Behçet patients with early intestinal involvement.

Autoantibodies against ß1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the ß1-adrenergic (ß1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. MATERIALS AND METHODS: We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. ß1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. RESULTS: A significantly higher percentage of patients positive for ß1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. ß1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of ß1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). CONCLUSIONS: Our study suggests that (1) the evaluation of ß1-AAb is useful to identify responders to CRT-D; (2) the presence of ß1-AAbs is in relationship with elevated renal function parameters.

Thrombosis in vasculitis: from pathogenesis to treatment.

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet's syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet'syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet's syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients.

Behçet's syndrome patients exhibit specific microbiome signature.

BACKGROUND AND AIMS: Behçet syndrome is a systemic inflammatory condition characterized by muco-cutaneous and ocular manifestations, with central nervous system, vascular and/or gastro-intestinal involvement. The association of microbiota with Behçet syndrome has not been shown yet. Our work was aimed to compare the gut microbiota structure and the profiles of short-chain fatty acids production in Behçet syndrome patients and healthy control relatives. METHODS: Here, we compared the fecal microbiota of 22 patients with Behçet syndrome and that of 16 healthy co-habiting controls, sharing the same diet and lifestyle by pyrosequencing of the V3-V4 hypervariable regions of the 16 rDNA gene and biochemical analyses. RESULTS: Our analyses showed significant differences in gut microbiota between Behçet patients and healthy cohabitants. In particular we found that Behçet's patients were significantly depleted in the genera Roseburia and Subdoligranulum. Roseburia showed a relative abundance value of 10.45±6.01% in healthy relatives and 4.97±5.09% in Behçet's patients, and Subdoligranulum, which reached a relative abundance of 3.28±2.20% in healthy controls, was only at 1.93±1.75% of abundance in Behçet's patients. Here we report, for the first time, that a peculiar dysbiosis of the gut microbiota is present in patients with Behçet syndrome and this corresponds to specific changes in microbiome profile. A significant decrease of butyrate production (P=0.0033) in Behçet's patients was demonstrated. Butyrate is able to promote differentiation of T-regulatory cells, and consequently the results obtained prompt us to speculate that a defect of butyrate production might lead to both reduced T-reg responses and activation of immuno-pathological T-effector responses. CONCLUSIONS: Altogether, our results indicate that both a peculiar dysbiosis of the gut microbiota and a significant decrease of butyrate production are present in patients with Behçet syndrome.

Skin CD30(+) T cells and circulating levels of soluble CD30 are increased in patients with graft versus host disease.

OBJECTIVE: To determine serum soluble CD30 (sCD30) levels in patients with graft versus host disease (GVHD). METHODS: Serum soluble CD30 levels and IgE levels were assayed by a sensitive ELISA in 57 patients with bone marrow transplantation, and in 44 healthy controls. We analyzed the type of effector T cells in patients with GVHD. RESULTS: Serum levels of sCD30 and serum IgE levels were significantly higher (p values <0.05) in patients with acute and chronic GVHD than in healthy controls. We found that CD30(+) T-cells are present in the skin of patients with GVHD. CONCLUSION: These results suggest that serum sCD30 levels may be helpful for the management of patients with bone marrow transplantation.