Fulya Ilhan

Th1 polarization of the immune response in uveitis in Behçet's disease

BACKGROUND It has been reported that abnormalities in the balance of T-helper cells type 1/2 (Th1/Th2) may account for the pathophysiology of human autoimmune diseases. The purpose of this study was to define the role of the Th1/Th2 balance in the pathogenesis of uveitis in Behçets disease (BD). METHODS From February 2003 to August 2005, we studied 31 patients with active BD. Of these patients, 21 (12 female, 9 male; mean age 35.5 [SD 10] years) presented with acute uveitis, and 10 (7 female, 3 male; mean age 34 [SD 11] years) presented with inflammatory arthritis but no prior uveitis attack. The control group consisted of 10 (7 female, 3 male; mean age 34.7 [SD 8] years) age-matched, healthy individuals. CD4+ CD26+ and CD4+ CD30+ cell surface expression of the peripheral blood CD4+ T lymphocytes was evaluated by analytic flow cytometry in order to determine percentages of Th1 and Th2 lymphocyte subsets. RESULTS The mean percentage of CD4+ CD26+ and CD4+ CD30+ cells was 26.27 (SD 6.18) % and 2.56 (SD 0.82) %, 17.42 (SD 5.90) % and 2.86 (SD 0.72) %, and 14.99 (SD 3.96) % and 3.11 (SD 1.25) % in BD with active uveitis, BD with inflammatory arthritis but no prior uveitis attack, and control groups, respectively. T-helper 1 (Th1) cell percentage was significantly higher in the BD with active uveitis group than the BD with arthritis and no prior uveitis attack group (p = 0.001). With respect to the percentage of CD30+ Th2 cells, there was no statistical difference between the 2 BD groups (p = 0.529) or among the 3 groups (p = 0.375). INTERPRETATION Th1 lymphocyte dominance in peripheral circulating blood may play a role in the pathogenesis of BD uveitis.

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-β levels in pregnant women with preeclampsia, and their relation with severity of disease

Abstract Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants. Methods: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version. Results: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p < 0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p < 0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age. Conclusions: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.

Lymphocyte Subpopulations in Pulmonary Tuberculosis Patients

Protection against Mycobacterium tuberculosis is based on cell-mediated immunity, most importantly involving CD4+ and CD8+ T-cell subsets. The aim of this study was to evaluate CD4+ and CD8+ T-cell profiles and CD19+ and CD3−CD(16+56)+ populations in patients with pulmonary tuberculosis. CD4+ and CD8+ T cells, B-lymphocytes, and natural killer (NK) cells were evaluated in 75 active (APTB) and 25 inactive (IPTB) pulmonary tuberculosis cases and 20 healthy subjects (HCs). The results were compared at different stages of antituberculosis treatment in the APTB patients and also according to X-ray findings in the newly diagnosed APTB patients. The percentages of CD4+ T cells were significantly lower (P < .01) and those of CD3−CD(16 + 56)+ cells were significantly higher (P < .01) in APTB patients than in HCs. CD8+ T cells were significantly decreased (P < .05), and CD3−CD(16+56)+ cells were significantly increased (P < .01), in IPTB patients compared to HCs. The percentages of CD4+, CD8+, CD3−CD19+, and CD3−CD(16+56)+ cells showed no differences at different times of the antituberculosis regimen, and different stages of newly diagnosed APTB patients. APTB patients have a reduced percentage of circulating CD4+ T cells and an increased percentage of NK cells compared with healthy individuals. These cells could play important roles in the immune response to M tuberculosis infection.

Immunological follow-up of hydatid cyst cases

Hydatid disease is caused by Echinococcus granulosus. In this study, we aimed to investigate the benefit of monitoring cases with hydatid cyst by means of immune components in patients in a long-term follow-up after surgery. Eighty-four preoperative and postoperative serum samples from 14 cases undergoing surgery for hydatid disease were evaluated in terms of immune parameters, such as total and specific IgE, IgG, IgM, IgA and complement. Total and specific IgE were determined by ELISA. Specific IgG levels were measured by indirect hemagglutination. Total IgG, IgM, IgA and complement (C3 and C4) were detected by nephelometry. Imaging studies were also carried out during the follow-up. In none of the patients hydatid cysts were detected during the follow-up. Total IgE levels in the sera of the patients decreased to normal six months after surgery. Although specific IgE against echinococcal antigens decreased one year after operation, levels were still significantly high. There were no changes in the levels of anti-Echinococcus IgG and total IgG in follow-up period. Additionally, other parameters, such as IgA, IgM, C3 and C4, were not affected.

The effect of infliximab, cyclosporine A and recombinant IL-10 on vitreous cytokine levels in experimental autoimmune uveitis.

BACKGROUND To identify the effect of infliximab, cyclosporine A and recombinant IL-10 in experimental autoimmune uveitis. MATERIALS AND METHODS Sixty male rats were assigned to five groups of 12 each. All the groups (except the control group) were administered 30 microg retinal-S antigen intraperitoneally. On the 14th day, after confirmation of uveitis with histopathological study, daily cyclosporine A injection was given in cyclosporine A treatment group and physiological serum in the uveitis-induced placebo treatment and control groups. In the infliximab treatment group, infliximab was administered on the 14th, 15th, 17th, 19th and 21st days. In the recombinant IL-10 treatment group, three doses of recombinant IL-10 were given four hours and a half hours before and eight hours after retinal-S antigen administration. On the 21st day of the study, all rats were sacrificed and vitreous cytokine levels (IL-1, IL-6, IL-8 and TNF-alpha) were studied with ELISA. RESULTS In the treatment groups, cytokine levels (IL-1, IL-6 and TNF-alpha) were significantly lower than the uveitis-induced placebo treatment group. Compared with the control group, there was no significant difference with respect to TNF-alpha and IL-8 in the infliximab treatment group; IL-8 in the cyclosporine A treatment group; IL-6 and IL-8 in the recombinant IL-10 treatment group. The drugs used did not significantly differ in respect to their effects on vitreous IL-6, IL-8 and TNF-alpha levels. CONCLUSION Cyclosporine A, infliximab and recombinant IL-10 reduce the vitreous cytokines levels. Among these drugs, recombinant IL-10, which is still in its experimental phase, might be considered as a new therapeutic agent.

What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility?

Implantation necessitates complex interactions among the developing embryo, decidualizing endometrium, and developing maternal immune tolerance and/or alterations in cellular and humoral immune responses. Overstimulation of T helper 1 (Th1) or Th2 cytokines in systemic and local environments, alterations of the prevalence of IL17 and regulatory T cell (Treg) cytokines have also been suggested to contribute to the pathogenesis of implantation failure. We aimed to investigate the plasma levels of IL4, IL6, IL10, TNFα, IFNγ, TGFβ, IL17, IL35, and SOCS3 in infertile and fertile women. This case-control study was conducted with 80 women suffering from unexplained infertility and 40 fertile women. Peripheral venous blood samples were drawn on day 21 of the menstrual cycle. The extracted plasma samples were assayed by an enzyme linked immunosorbent assay. Statistical analysis was performed using SPSS version 16.0. Our main findings were as follows: despite the significantly high IL17 and IL35 plasma levels of infertile women, IL35/IL17 ratio was significantly lower in the infertile group compared with that in the fertile group; SOCS3 plasma levels showed an inverse relation with plasma levels of all cytokines except IL35; increased plasma IL17 levels (>3.42 pg/mL) have a negative impact on fertility; TNFα/IL10, IFNγ/IL10, IFNγ/IL6, and IFNγ/IL4 ratios were significantly higher in infertile group compared with those in the fertile group. It is not possible to show the major immunological factor(s) of unexplained infertility, but our findings point out that the decreased suppressor activity of the immune system may play a role in implantation failure.

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Abstract Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls. Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay. Results: The mean age of RPL and control cases were 31.6 ± 0.6 and 32.1 ± 0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk. Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

Mycoplasma Pneumoniae and Chlamydia Pneumoniae Seropositivity in Patients With Age-Related Macular Degeneration

Background To determine a possible relation between Mycoplasma pneumoniae (MP) or Chlamidia pneumoniae (CP) seropositivity and age-related macular degeneration (AMD). Methods Sixty patients (20 wet AMD, 20 dry AMD and 20 non-AMD controls) were included in the study. Serum samples were collected for analysis of IgM and IgG antibody seropositivity for CP and MP by enzyme-linked immunosorbent assay (ELISA). Comparison of the distribution of seropositivity of these antibodies among patients with wet and dry AMD, and controls was performed. A prospective comparative clinical trial was applied. Results There was no major difference in the distribution of IgM and IgG seropositivity to CP and MP in patients with wet and dry AMD, and in controls (p > 0.05). Conclusions We found no significant association between MP as well as CP antibody titers and AMD. It seems that MP or CP infection is not a risk factor for AMD. Keywords Mycoplasma pneumoniae; Chlamydia pneumoniae; Age-related macular degeneration; Serology

Are there any differences between Preeclamptic and Healty Pregnant Women for Serum and Placental Levels of Milk Fat Globule Epidermal Growth Factor-8 and Suppressor of Cytokine Signaling-3?

Preeclampsia (PE) is a placenta-induced inflammatory disease associated with maternal and fetal morbidity and mortality [1, 2]. The mechanisms underlying PE is still unclear but generally accepted that in PE, the factors released from placenta into the maternal circulation induce inflammation [3]. Significantly elevated circulating factors in PE include cytokines and antiangiogenic factors and these factors modulate trophoblast invasion [4]. The hypothesis produced by Ahmed and Ramma suggested that preeclampsia might be result of the imbalance between new-onset inflammatory state and endogenous protective pathways during pregnancy [5]. Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8), a novel endometrial epithelial protein, found to have multiple biological functions against inflammation [6,7]. MFG-E8 binds to apoptotic cells, enhances the phagocytosis of apoptotic cells by macrophages and provides an anti-inflammatory function [8,9]. Topical recombinant MFG-E8 treatment induces resolution of wound inflammation, and improvement in angiogenesis [10]. Suppressor of cytokine signaling-3 (SOCS-3) plays an important role in negative regulation of inflammatory response [11]. Decreased serum and placental SOCS-3 levels in preeclampsia may account for the increased inflammatory response in PE [1214]. We hypothesize that both of MFG-E8 and SOCS3 levels may decrease or increase either being result or reason of PE. And we compared the serum and placental levels of MFG-E8 and SOCS3 between preeclampsia and gestational-age matched healthy pregnant women.

Psöriazisli hastalarda deri lezyonlarında T hücreleri ve periferik kanda sitokin düzeyleri

Objectives: To compare endothelial changes after penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) in clear corneal graft. Methods: In this study, fifty six eyes undergone DALK (DALK Group) and eighty two eyes undergone PK (PK Group) due to various reasons are included. After operation at 1st, 12th, 24th and 36th month central corneal endothelial cell density (CD) and variability coefficient(CV) value examined by specular microscopy of clear graft which have not had additional surgery, greft rejection or glaucoma during follow up period were compared. Results: Endothelial cell density in DALK group were 2426p587 cell/mms 2289p579 cell/mms, 2222p541 cell/mms, 2175p521 cell/mms, in PK group were 2595p589 cell/mms, 2064p583 cell/mms, 1759p510 cell/mms 1509p494 cell/mms at 1st, 12th, 24th and 36th month respectively. Decrease in CD values were 5.9% at 12th month, 7.5% at 24th month and 9.4% at 36th month comparing with first month in DALK group. Decrease in CD values were 18.4% at 12th month, 30.2% at 24th month and 40.3% at 36th month comparing with first month in PK group. Variability coefficient (CV) values in group DALK were 23.3p6.2, 24.2p6.4, 24.2p6.1 and 24.5p5.6 at 1st,12th, 24th and 36th month respectively. Variability coefficient (CV) values in group PK were 19.6p3.4, 23.2p5.4, 25.9p6.2 and 27.5p5.7 at 1st,12th, 24th, and 36th months respectively. Conclusion: More polymegatism and more decrease in endothelial cell density with time were assessed in grafts undergone PK compared with grafts undergone DALK.Objectives: The aim of this study was to determine the effect of fracture type and angular deterioration on the outcome of calcaneal fractures. Materials and methods: Thirty-two patients (23 males, 9 females; mean age 45 years) with calcaneus fractures retrospectively reviewed. Twenty-four fractures were closed, and eight fractures were open. Bohler and Gissane angles were measured using patient’s before, and after reduction X-ray films. According to the EssexLopresti classification there were three type I, 14 type II, and 15 type III fractures. Five patients were treated with casting (Group I), 19 patients with closed reduction K-wire application (Group II), and 8 patients with plate fixation. Final clinical outcome were assessed by Maryland Foot Score. Mean follow-up period was 109 weeks.Amac: Bu calismada kalsipotriol-betametazon dipropionat ile tedavi edilen plak psoriazisli olgularda doku duzeyinde hucresel immunitenin ve serumda sitokin duzeylerinin rolunun arastirilmasi amaclandi. Gerec ve yontem: Calismaya plak tip psoriazisli 20 olgu alindi. Hastalarin tedavi oncesi ve sonrasi psoriatik lezyonlari ile saglam deriden biyopsi ve periferik kan ornekleri alindi. Bulgular: Immunohistokimyasal incelemede, CD4+, CD8+ ve CD25+ T lenfositler, tedavi oncesi lezyonlu dokuda saglam doku ve tedavi sonrasi doku ile kiyaslandiginda anlamli bir sekilde yuksekti (sirasiyla, p0.05). Sonuc: Calismamizda lezyonlu deride CD4+ ve CD8+ hucre birikimi oldugunu ve CD4+ T lenfositlerin daha hâkim hucre grubu oldugu gosterildi. Uygulanan topikal tedavinin etkinligine paralel olarak lezyonlarda duzelme olmasi ve lezyonlu bolgelerde CD4+ ve CD8+ T hucrelerinde anlamli bir azalma meydana gelmesi, Th lenfositlerin hastaligin immunopatogenezinde onemli rolunun oldugu tezini desteklemektedir. Ancak, sonuclarimiz, hastaligin kronik ozelligi ile uyumlu olarak T hucrelerin dokuda yine de yeterince kaldigini ve topikal tedavinin hastaligin aktivasyonunu engelleyemedigini gostermektedir.