Successful response in a case of severe pustular psoriasis after interleukin-1ß inhibition.

Generalized pustular psoriasis (GPP) is a severe type of psoriasis accompanied by systemic and often life-threatening manifestations. The efficacy of the interleukin (IL)-1 antagonist anakinra in cases of GPP underscores the role of IL-1 in disease pathogenesis. We present a case of a middle-aged man who developed an abrupt and severe form of GPP with severe eosinophilia and cholestatic hepatitis. The patient received salvage treatment with a combination of glucocorticoids, hydroxyurea and imatinib, while administration of the IL-1 inhibitor anakinra resulted in remission of hepatitis and a significant skin improvement. However, due to persistent hypersensitivity skin reactions, anakinra was withdrawn and replaced with the anti-IL-1ß antagonist canakinumab. As a result of canakinumab, the patient's skin completely cleared, while no systemic manifestations recurred. After 1 year of continuous canakinumab therapy, the patient remained virtually free of symptoms, while the drug was well tolerated.

Immunity to brucellosis.

Resistance to intracellular bacterial pathogens such as Brucella spp. relies on cell-mediated immunity, which involves activation of the bactericidal mechanisms of antigen-presenting cells (macrophages and dendritic cells) and the subsequent expansion of antigen-specific CD4+ and CD8+ T-cell clones. Brucella antigens induce the production of T helper type 1 (Th1) cytokines, and an adequate Th1 immune response is critical for the clearance of Brucella infection. Studies on experimental and human brucellosis indicate that interferon-gamma (IFNgamma) is the principal cytokine active against Brucella infection. On the other hand, Brucella has evolutionarily developed diverse evasion strategies to avoid the host's innate and adaptive immunity in order to establish an intracellular niche for long-term parasitism. Disturbances of the Thl response and anergy have been described in patients with chronic brucellosis, and are associated with poor outcome. Accordingly, chronic brucellosis represents a challenge for the study of immune mechanisms against Brucella and the development of novel therapeutic or vaccination approaches.

CD4+/CD25+ T-Lymphocytes and Th1/Th2 regulation in dilated cardiomyopathy.

OBJECTIVE: Autoimmune mechanisms are often involved in the pathogenesis of Dilated Cardiomyopathy (DCM) and Th1 immune response against cardiac antigens plays a pivotal role in disease development. METHODS: IL-2 receptor (CD4+/CD25+) and cytokines IL-2, IFN-γ, IL-10 were studied in 42 patients (17 with DCM - DCM group, 10 patients with hypertrophic cardiac disease - HCD group, and 15 healthy volunteers - Control group). DCM group was subdivided in: DCM-1 (9 patients with recent disease onset) and DCM-2 (8 patients with chronic DCM). The % CD4+/CD25+ T-lymphocytes were analyzed by double fluorescence flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-cultures with/without 5 and 10 microgr of human cardiac myosin. The cytokines were measured using Enzyme-Linked Immunosorbant Assay (ELISA) method. RESULTS: Ex vivo analysis: In DCM group, CD4+/CD25+ T-cells significantly increased compared to other groups (p<0.05), due exclusively to DCM-2 subgroup (p=0.019). In PHA cultures in DCM-2 subgroup CD4+/CD25+ T-lymphocytes were significantly increased compared to all other groups (p<0.001). The addition of myosin in the cultures of DCM-2 subgroup maintained the same result. In cultures supernatants in DCM-2 subgroup, IL-2 levels were impressively increased compared to DCM-1 subgroup (p=5.91x10-6), HCD and Control groups (p<0.001). Addition of antigen decreased significantly IL-2 levels in DCM-2 subgroup (p=0.01). IFN-γ levels followed the same pattern of alterations. IL-10 levels were significantly increased in both DCM subgroups compared to HCD and Control groups (p<0.05). CONCLUSIONS: Increased peripheral CD4+/CD25+ T-cells found in chronic DCM could be a useful prognostic marker in DCM progress. Increased synthesis of IL-2 and IFN-γ and varying IL-10 levels reflects a Th1 pattern of immune response during chronic disease and implies active cellular immunity process, related to poor prognosis. Thus, analysis of the Th1/Th2 phenotype may be useful in disease monitoring in patients with DCM. This paper is a part of PhD thesis. It has been published at the abstract book of the Acute Cardiac Care congress 2010.

Genetic polymorphism study of regulatory B cell molecules and cellular immunity function in an adult patient with Common Variable Immunodeficiency.

A 43 year old female patient presented for recurrent bacterial lower respiratory infections. A research for immunodeficiency status revealed total hypogammaglobulinemia, reduced IgG1, IgG2, IgG3 subclass levels, and low number of B lymphocytes (CD19+). Common Variable Immunodeficiency (CVID) 11.2 category was diagnosed according to recent criteria of primary immunodeficiencies (PID). Further immunological study consisting of genetic polymorphism of genes relating to differentiation, activation and function of B cells (ICOS, BAFF receptor BCMA and TACI) was performed, which did not reveal any related mutations. T cell parameters and Th1/Th2 cytokine network did not show any disturbances. It is postulated that probable endstage B cell differentiation defects should be investigated. The patient receives IVIGs replacement thereafter and the rate and severity of infections have significantly improved.

Adamantiades-Behcet disease (ABD) in northern Greece patients: experience from a single center.

UNLABELLED: OBJECTIVE-METHODS: Adamantiades-Behcet disease (ABD) is a multi-systemic vasculitis of unknown origin, with a characteristic geographic distribution, that affects vessels of all kinds and sizes and is characterized by recurrent mucosal, skin and ocular lesions. In the present study, a series of 36 patients from Northern Greece is analyzed retrospectively in regard to the epidemiological, clinical and immunological parameters. RESULTS: All patients had recurrent oral ulcerations (36/36, 100%), while 23/36 (63.9%) experienced genital ulcerations and 22/36 (61.1%) developed ocular disease. Skin manifestations were observed in 23/36 patients (63.9%) and pathergy test was found positive in 14/36 patients (38.9%). Other manifestations included central nervous system involvement, recurrent genitourinary inflammations, arthralgias and superficial thrombophlebitis. Laboratory findings were not specific, partly reflecting the severity of inflammation. Ocular disease was more often observed in HLA-B51 (+) patients (20/31, 64.5%) than in HLA-B51 (-) patients. Standard of care (SOC) treatment consisted of cyclosporine A, azathioprine, methylprednisolone and aspirin, whereas refractory disease was treated with intravenous pulses of methylprednisolone and cyclophosphamide. Occasionally, anti-TNF agents (infliximab) were applied to treat refractory ocular disease. CONCLUSION: The findings of the present study come in agreement with those reported for other Mediterranean series. HLA-B51 seems to predispose to more severe disease, while early therapeutic intervention is beneficial for these patients.

CD80/CD28 co-stimulation in human brucellosis.

Despite treatment, 10-30% of brucellosis patients develop chronic disease, characterized by atypical clinical picture and/or relapses. A defective T helper 1 (Th1) response and a low [corrected] percentage of CD4(+)/CD25(+) cells have been described in chronic brucellosis patients. CD80/CD28 co-stimulation is critical for an efficient Th1 response and has not been studied previously in human brucellosis. In order to investigate the role of CD80/CD28 co-stimulation, 13 acute brucellosis patients (AB), 22 chronic brucellosis patients (CB, 12/22 relapsing type-CB1 and 10/22 atypical type-CB2), 11 'cured' subjects and 15 healthy volunteers (controls) were studied. The percentage of CD4(+)/CD28(+) T lymphocytes and CD14(+)/CD80(+) monocytes were analysed by flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-stimulation with or without heat-killed Brucella abortus (HkBA). Ex vivo analysis showed no differences between all groups studied. PHA stimulation up-regulated the percentage of CD80(+) monocytes in AB compared to 'cured' subjects and controls (P < 0.001), although the proportion of CD4(+)/CD28(+) cells did not alter. A higher percentage of CD80(+) monocytes was observed in the CB1 subgroup, compared to AB, 'cured' subjects and controls (P = 0.042, < 0.001 and < 0.001, respectively). CB2 was characterized by a lower percentage of CD80(+) monocytes in comparison to CB1 (P = 0.020). HkBA in PHA cultures down-regulated the percentage of CD80(+) monocytes compared to PHA alone in all groups, especially in AB and CB patients (P < 0.001 and P = 0.007, respectively). In conclusion, the diminished percentage of CD4(+)/CD25(+) T cells in CB is not associated with inadequate CD80/CD28 co-stimulation. We speculate that differential frequency of CD80(+) monocytes after PHA stimulation could serve as a qualitative parameter of disease status, related to the different clinical forms of chronic brucellosis.

Concurrent relapsing central nervous system and ocular involvement in a case of life-threatening Adamantiades-Behçet Disease (ABD).

Adamantiades-Behçet disease (ABD) is characterised by oral and genital ulcerations, skin lesions and ocular manifestations and, rarely, by central nervous system (CNS) involvement. Neuro-Behçet disease (NBD) is categorised to parenchymal or non-parenchymal, while combined CNS disease is rarely reported in the literature. A case of NBD, with severe relapsing ocular and neurological disease of combined pattern is presented. Neurological complications included brainstem manifestations, as well as neurovascular involvement, while ocular involvement consisted of bilateral uveitis and branch retinal vein occlusion. Manifestations responded to corticosteroid plus cyclophosphamide pulse therapy. Maintenance therapy included cyclosporine A, azathioprine and corticosteroids. Case individualities are discussed, focusing on scepticism concerning treatment of NBD relapses in the long term.

Intradural, eextramedullary tuberculoma of the spinal cord as a complication of tuberculous meningitis.

An unusual case of an intradural, extramedullary spinal cord tuberculoma, as a complication of tuberculous meningitis caused by a strain susceptible to major anti-TB drugs, is described in a previously healthy, HIV-negative, 27-year-old male. The tuberculoma was detected by magnetic resonance imaging (MRI) while the patient was under conventional anti-tuberculous (anti-TB) therapy. Histopathology confirmed the diagnosis. Despite the anti-TB treatment and the surgical resection, intramedullary spreading occurred. Finally, a favorable response was achieved by prolongation of treatment accompanied by the administration of ofloxacin and cycloserine.

Effect of bacterial extracts on the immunologic profile in chronic relapsing brucellosis patients.

Brucellosis is an intracellular bacterial disease of common incidence in Greece. Existing therapy is inadequate and a considerable proportion of patients become chronically ill and are immunocompromised. Defects of the monocyte-macrophage system and T-lymphocytes have been described in chronic brucellosis and can be restored after immunopotentiation therapy. Bacterial (Klebsiella pneumoniae) extracts exert immunostimulating effects on the monocyte-macrophage system and have already been used successfully in the prevention of common infections of the respiratory track. So we decided to investigate: 1) Leukocyte Migration Index (LMI), 2) Monocyte-macrophage random and directed migration against both nonspecific leukoattractant (casein) and disease specific antigens (Brucella melitensis, Brucella abortus), 3) Monocyte-macrophage phagocytosis index, 4) Delayed-type hypersensitivity (skin tests) against seven antigens, before (TO), during (T2), and after (T3) oral administration of bacterial (Klebsiella pneumoniae) extracts at conventional doses plus antibiotics or not. Our results show that: 1) Concerning the LMI, 4 out of 19 remained anergic at time T3 of the study, 2) Random migration was not affected during treatment, 3) Directed migration increased significantly without reaching control group values, 4) Phagocytosis index increased significantly and reached normal values at T3, 5) Delayed type hypersensitivity reactions (skin tests) increased significantly at the end of the study period. Reaction against Tuberculin and Candida antigens showed the most pronounced increase in skin reactivity. In conclusion, bacterial (Klebsiella pneumoniae) extracts improve peripheral monocyte locomotion and restore phagocytosis index, thus enhancing cellular immunity parameters in immunocompromised chronic brucellosis patients.