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Background: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood., Objective: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve., Study Design: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm., Results: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm., Conclusion: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterized by focal or diffuse organ infiltration of IgG4-bearing plasma cells. The diagnosis of IgG4-RD is based on a combination of clinical, serologic, radiologic, and histopathologic findings. IgG4-RD has been reported to affect almost all organ systems. The kidney is the most frequently involved of the genitourinary organs. The most common renal manifestation of IgG4-RD is IgG4-RD tubulointerstitial nephritis, followed by membranous glomerulonephropathy and, less frequently, obstructive nephropathy involving the renal pelvis, ureter, or retroperitoneum. Renal parenchymal lesions may appear as multiple nodular lesions, diffuse patchy infiltrative lesions, or a single nodular lesion. Multiple small nodular cortical lesions are the most common imaging findings of IgG4-RD involving the kidney. Renal pelvic, sinus, or perinephric lesions can also occur. IgG4-RD involvement of other genitourinary organs including the ureter, bladder, urethra, and male and female reproductive organs is rare compared with kidney involvement but may show variable imaging findings such as a localized mass within or surrounding the involved organ or diffuse enlargement of the involved organ. Imaging findings of IgG4-RD involving the genitourinary system are nonspecific but should be differentiated from inflammatory and neoplastic lesions that mimic IgG4-RD. The online slide presentation from the RSNA Annual Meeting is available for this article. © RSNA, 2020.

Purpose: Imaging features of immune-mediated genitourinary diseases often overlap, and the same disease may manifest in different ways, so understanding imaging findings in the context of the patient's entire clinical picture is important in providing the correct diagnosis., Methods: In this article, diseases mediated by the immune system which affect the genitourinary system are reviewed. Examples of immune-mediated genitourinary disease including IgG4-related disease, post-transplant lymphoproliferative disorder, immunodeficiency-associated lymphoproliferative disorder due to immunosuppressive and immunomodulatory medications, lymphoma, leukemia, myeloma, amyloidosis, and histiocytosis., Results: Clinical and imaging features will be presented which may help narrow the differential diagnosis for each disease., Conclusion: Recognition of immune-related genitourinary disease is important for appropriate medical management as they may mimic other diseases both by imaging and clinical presentation.

Background: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases., Objectives: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition., Methods: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored., Results: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO + cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO + cells did not overlap with those of CD1a + Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO + cells in the HPV - site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation., Conclusions: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment., (© 2017 British Association of Dermatologists.)

The own observations results of urogenital, gastrointestinal and nasopharyngeal infectious factors that cause the development of reactive arthritis (PeA) are being presented. The greatest contribution to the development of this disease make Chlamidia trachomatis (36%), Streptococcus haemolyticus (pyogenes) (19%) and hepatitis viruses B and C (10%). As a result of the research a number of kinetic parameters of arginase and NO-synthase reactions in peripheral blood lymphocytes of patients with reactive arthritis was identified. The authentic increase of arginase activity in 3.3 times and eNO-synthase activity decrease by 1,9 times in peripheral blood lymphocytes of patients with PeA, compared to practically healthy donors were determined. Increased activity of arginase and iNO-synthase of lymphocytes indicates changes in immune cells functional activity, which may be due to impaired metabolic and regulatory processes in these cells caused by a bacterial or viral infection.

Animal models of human disease are important tools in many areas of biomedicine; for example, in infectious disease research and in the development of novel drugs and medical devices. Most studies involving animals use rodents, in particular congenic mice, due to the availability of a wide number of strains and the ease with which they can be genetically manipulated. The use of mouse models has led to major advances in many fields of research, in particular in immunology but despite these advances, no animal model can exactly reproduce all the features of human disease. It is increasingly becoming recognised that in many circumstances mice do not provide the best model and that alternative species may be more appropriate. Here, we describe the relative merits of sheep as biomedical models for human physiology and disease in comparison to mice, with a particular focus on reproductive and respiratory pathogens., (Copyright © 2014. Published by Elsevier Ltd.)

Hosts are expected to incur several physiological costs in defending against parasites. These include constitutive energetic (or other resource) costs of a defence system, facultative resource costs of deploying defences when parasites strike, and immunopathological costs of collateral damage. Here, we investigate the evolution of host recovery rates, varying the source and magnitude of immune costs. In line with previous work, we find that hosts paying facultative resource costs evolve faster recovery rates than hosts paying constitutive costs. However, recovery rate is more sensitive to changes in facultative costs, potentially explaining why constitutive costs are hard to detect empirically. Moreover, we find that immunopathology costs which increase with recovery rate can erode the benefits of defence, promoting chronicity of infection. Immunopathology can also lead to hosts evolving low recovery rate in response to virulent parasites. Furthermore, when immunopathology reduces fecundity as recovery rate increases (e.g. as for T-cell responses to urogenital chlamydiosis), then recovery and reproductive rates do not covary as predicted in eco-immunology. These results suggest that immunopathological and resource costs have qualitatively different effects on host evolution and that embracing the complexity of immune costs may be essential for explaining variability in immune defence in nature., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs.

Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated., (© 2014 John Wiley & Sons Ltd.)

Objective: To test the adjuvant use of the combination of N-palmitoylethanolamine and transpolydatin in the medical treatment of endometriotic pain., Study Design: We enrolled 47 patients admitted to the Outpatient Endometriosis Care Unit of Ferrara University from January 2011 to December 2011. They were divided into two groups according to the endometriosis site (group A: recto-vaginal septum; group B: ovary). One tablet, containing 400 mg of micronized N-palmitoylethanolamine plus 40 mg transpolydatin, was administered twice daily on a full stomach for 90 days. Each patient was requested to grade the severity of dysmenorrhea, chronic pelvic pain, dyspareunia and dyschezia using a 0-10 cm visual analogic scale prior to beginning treatment (T0), after 30 days (T1), 60 days (T2) and 90 days (T3). The continuous and categorical variables were compared, respectively, using Student's t-test and the chi-square test. Analysis of variance for repeated measures was used to verify the reduction of endometriotic pain., Results: The intensity of endometriotic pain decreased significantly for both groups (p<0.0001). The efficacy of drug treatment was significant after 30 days. Pain intensity decreased equally in the two groups except for dysmenorrhea, which was reduced more rapidly in group B., Conclusions: The combination of N-palmitoylethanolamine and transpolydatin reduced pain related to endometriosis irrespective of lesion site. It had a marked effect on chronic pelvic pain determined by deep endometriosis and on dysmenorrhea correlated to ovarian endometriosis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Problem: Untreated celiac disease (CD) is often associated with early miscarriages, infertility, and alterations in menstrual cycle. Tissue transglutaminase (tTG) antibodies could be involved by interfering with tTG transamidating activity and/or biological functions mediated by its interaction with fibronectin (FN)., Method of Study: The correlation between the presence of extra-digestive disorders and the reactivity of sera against tTG-FN and its effects on tTG transamidating activity was analyzed in a group or 50 women with recently diagnosed CD., Results: Heterogeneous behavior was observed among serum samples derived from patients with different complaints, suggesting that differences in fine specificity patterns could condition clinical outcome. Sera from women with gynecological and/or obstetric problems induced significant inhibition of in vitro enzymatic activity in comparison with those without these kinds of disorders., Conclusions: The significant correlation observed between serum effects and clinical profile suggests a putative involvement of tTG-specific antibodies in gynecological and/or obstetric disorders during active CD., (© 2011 John Wiley & Sons A/S.)

We have previously shown that individuals infected with Chlamydia trachomatis can develop a robust antibody response to a Chlamydia type III secretion effector protein called Tarp and that immunization with Tarp induces protection against challenge infection in mice. The current study aimed to map the immunodominant regions of the Tarp protein by expressing 11 fragments of Tarp as glutathione S-transferase (GST) fusion proteins and detecting the reactivity of these fusion proteins with antisera from patients infected with C. trachomatis in the urogenital tract or in the ocular tissue and from rabbits immunized with C. trachomatis organisms. A major immunodominant region was strongly recognized by all antibodies. This region covers amino acids 152 to 302, consisting of three repeats (amino acids 152 to 201, 202 to 251, and 252 to 302). Each of the repeats contains multiple tyrosine residues that are phosphorylated by host cell kinases when Tarp is injected into host cells. Several other minor immunodominant regions were also identified, including those comprising amino acids 1 to 156, 310 to 431, and 582 to 682 (recognized by antisera from both humans and rabbits), that comprising amino acids 425 to 581 (recognized only by human antisera), and that comprising amino acids 683 to 847 (preferentially recognized by rabbit antisera). This immunodominance was also confirmed by the observations that six out of the nine monoclonal antibodies (MAbs) bound to the major immunodominant region and that the other three each bound to one of the minor fragments, comprising amino acids 1 to 119, 120 to 151, and 310 to 431. The antigenicity analyses have provided important information for further understanding the structure and function of Tarp.

Levels of expression of hBD-1 gene (beta-defensin 1) and Toll-like receptors (TLR1, TLR2, TLR6) in cells of cervical mucosa in healthy nonpregnant and healthy pregnant women as well as in pregnant women with urogenital infection was measured by developed RT-PCR systems. During normal pregnancy compared with nonpregnant women, increase of TLRs genes expression which was correlated with increase of hBD-1 gene expression was observed. During urogenital infection in pregnant women compared with healthy pregnant, 10- fold and 50-fold increase of TLR1 and TLR2 genes expression respectively was associated with 2.5-fold decrease of hBD-1 gene expression in cervical mucosa. In group of women with untrauterine infection more marked increase of TLRs genes expression was observed. Thus significant changes (TLRs, antimicrobial peptides, cytokines etc.) in cells of cervical mucosa can be used as prognostic criteria for development of intrauterine infection.

There is increasing evidence that certain probiotic strains can be useful in improving human health. The use of probiotics has received attention as a natural way of restoring body's normal microbiota, and an alternative and inexpensive way of preventing or treating infectious diseases without side effects. The best-documented clinical application of probiotics comes from trials on the treatment of gastrointestinal infections, mainly infectious diarrhoea. The enhancement of local as well as systemic immune responses by probiotics also offers new opportunities for probiotics in preventing infections at distal mucosal surfaces, such as those in the oral cavity, respiratory and urogenital tracts. The underlying mechanisms of probiotics are still unclear, but may include strengthening of the non-immunological gut barrier, interference with pathogen adhesion and growth inhibition, and the enhancement of the local mucosal immune system in the gut, as well as of the systemic immune response.

The aim of our research was to assess clinical-immunological properties of disease course and efficiency of complex etiotropic, enzyme-immunomodification therapy in women with urogenital chlamydiosis. Out of examined 818 women chlamydia was found in 276. The diagnoses of chlamydiosis in all women was assessed using the following methods: immuno-enzymatic, immunofluorescent and DNA-hybridization. Immune responses were studied in regard of forms and severity of the disease and its dynamics, as well as the regimens of treatments and their results. Vilkoxon-Mann-Witney non-parametric criterion U was used for statistical evaluation of the results. For measuring of identity of the various forms of treatment Spirman's coefficient r was used. Urogenital chlamydiosis is characterised by expressed misbalance of immune response of depressive character, the intensity of which depends upon the severity of genital pathology and obstetric anamnesis as well. Oral form of plaferon--LB enhances the immune-competent ability of the organism. The most expressive clinical effect was received using the combination of the antibiotic, enzymes and immuno-correction (95%).

Background: CD14 has been postulated to play a role in chlamydial immunity and immunopathology. There is evidence to support this role in human infections but its function in a mouse model has not been investigated., Methods: Female CD14 gene knockout and C57BL/6J wild type mice were infected intravaginally with Chlamydia muridarum. The infection course was monitored by detection of viable chlamydiae from serially collected cervical-vaginal swabs. The sequela of tubal factor infertility was assessed using hydrosalpinx formation as a surrogate marker., Results: A significantly abbreviated infection course was observed in the CD14 gene knockout mice but hydrosalpinx formation occurred at similar rates between the two groups., Conclusion: Involvement of CD14 during chlamydial infection impedes infection resolution but this does not affect the sequela of infertility as assessed by hydrosalpinx formation.

Using antibodies raised with chlamydial fusion proteins, we have localized a protein encoded by hypothetical open reading frame CT813 in the inclusion membrane of Chlamydia trachomatis. The detection of the C. trachomatis inclusion membrane by an anti-CT813 antibody was blocked by the CT813 protein but not unrelated fusion proteins. The CT813 protein was detected as early as 12 h after chlamydial infection and was present in the inclusion membrane during the entire growth cycle. All tested serovars from C. trachomatis but not other chlamydial species expressed the CT813 protein. Exogenously expressed CT813 protein in HeLa cells displayed a cytoskeleton-like structure similar to but not overlapping with host cell intermediate filaments, suggesting that the CT813 protein is able to either polymerize or associate with host cell cytoskeletal structures. Finally, women with C. trachomatis urogenital infection developed high titers of antibodies to the CT813 protein, demonstrating that the CT813 protein is not only expressed but also immunogenic during chlamydial infection in humans. In all, the CT813 protein is an inclusion membrane protein unique to C. trachomatis species and has the potential to interact with host cells and induce host immune responses during natural infection. Thus, the CT813 protein may represent an important candidate for understanding C. trachomatis pathogenesis and developing intervention and prevention strategies for controlling C. trachomatis infection.

The available chlamydial genome sequences have made it possible to comprehensively analyze host responses to all chlamydial proteins, which is essential for further understanding of chlamydial pathogenesis and development of effective chlamydial vaccines. Microplates arrayed with 156 Chlamydia trachomatis fusion proteins were used to evaluate antibody responses in women urogenitally infected with C. trachomatis. Based on both the antibody recognition frequency and titer, seven chlamydial antigens encoded by open reading frames (ORFs) CT089, CT147, CT226, CT681, CT694, CT795, and CT858, respectively, were identified as relatively immunodominant; six of these are encoded by hypothetical ORFs. Antibody binding to these chlamydial fusion proteins was blocked by C. trachomatis-infected but not by normal HeLa cell lysates or irrelevant bacterial lysates. These results have revealed novel immune-reactive chlamydial antigens, not only indicating that the hypothetical ORF-encoded proteins are expressed during chlamydial infection in humans but also providing the proof of principle that the fusion protein-based approach can be used to profile human immune responses to chlamydial infection at the whole-genome scale.

A complex clinico-instrumental and immuno-microbiological examination of 433 reproductive age women was performed. The results show that a lingering and relapsing chlamydian infection in women with an exacerbation of a chronic inflammatory urogenital disease develops against the background of disturbances in the anti-infective resistance system (AIRS), and is characterized by combination of chlamydian infection with other sexually transmitted infections and the presence of dysbiosis. The immunological aspects of this process consist in almost a total absence of neutrophiles' ability to digest a bacterial antigen, and incompleteness of phagocytosis, in general. These changes may be connected with a low immunogenicity and intracellular parasitizing of chlamydiae, on the one hand, and with primary incompetence of the subjects' AIRS, on the other. From a microbiological point of view, this is manifested by complete combined urogenital and colon dysbiosis.

Abnormalities in the cellular immunity chain (CIC) were found in 63.04% of patients with urogenital chlamydiosis (UGC) within a study of cellular immunity in patients with the above pathology. According to the study results, the below listed were the main CIC impairments: a lack or reaction to the inducer of T-helpers (CD3+ and CD4+), and to activated T-lymphocytes (CD3+ and CD25+); higher counts of cytotoxic T-lymphocytes (CD3+ and CD8+), a higher content of B-lymphocytes (CD3+ and CD19+, and lower counts of NK-cells (CD3- and CD56+). However, research of the lymphocyte subpopulation alone is not enough to evaluate adequately the immune system of a patient. In order to choose an adequate scheme for the treatment of UGH patients it is necessary to undertake a study of the immune status that should comprise, apart CIC investigations, the following: humoral immunity, phagocyte function, factors of non-specific body resistance and cytokine status.

The interferon status was studied in 54 patients with urogenital chlamydiosis, presenting with disturbances in the reproductive system. The blood serum content of gamma-interferon was 32-fold in the above patient population vs control subjects on conventional therapy. Supplementing such a therapy with cycloferon, an inducer of endogenous interferon, and with immunomodulin have been shown to activate production of interferon.

The results of complex treatment of 235 patients with persisting urogenital chlamidial infection are presented. The treatment regime included immunotropic agent interferone alfa-alpha 2b and antibiotic azithromycin (Sumamed, "Pliva", Croatia) 1 g per day 3 times every 7 days. Chlamidial persistence diagnosis was performed by culture method (determination of small cytoplasmic inclusions), by the method of immune fluorescence and PCR. The treatment provided positive influence on immune status (amount of CD4+; HLA-DR+ cell and IgA level normalized after the treatment). In 3 months after the treatment only 2 cases of Chlamydia trachomatis infection recurrence were registered. Treatment efficacy achieves 94.8 per cent.

It has been previously reported that although inducible nitric oxide synthase (iNOS) gene knockout (NOS2(-/-)) mice resolve Chlamydia trachomatis genital infection, the production of reactive nitrogen species (RNS) via iNOS protects a significant proportion of mice from hydrosalpinx formation and infertility. We now report that higher in vivo RNS production correlates with mouse strain-related innate resistance to hydrosalpinx formation. We also show that mice with a deletion of a key component of phagocyte NADPH oxidase (p47(phox-/-)) resolve infection, produce greater amounts of RNS in vivo, and sustain lower rates of hydrosalpinx formation than both wild-type (WT) NOS2(+/+) and NOS2(-/-) controls. When we induced an in vivo chemical block in iNOS activity in p47(phox-/-) mice using N(G)-monomethyl-L-arginine (L-NMMA), a large proportion of these mice eventually succumbed to opportunistic infections, but not before they resolved their chlamydial infections. Interestingly, when compared to WT and untreated p47(phox-/-) controls, L-NMMA-treated p47(phox-/-) mice resolved their infections more rapidly. However, L-NMMA-treated p47(phox-/-) mice lost resistance to chronic chlamydial disease, as evidenced by an increased rate of hydrosalpinx formation that was comparable to that for NOS2(-/-) mice. We conclude that phagocyte oxidase-derived reactive oxygen species (ROS) regulate RNS during chlamydial urogenital infection in the mouse. We further conclude that while neither phagocyte oxidase-derived ROS nor iNOS-derived RNS are essential for resolution of infection, RNS protect from chronic chlamydial disease in this model.

HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism. Three HLA-A2-restricted epitopes and two HLA-B51-restricted epitopes were identified in serovar E-MOMP. One of the five epitopes spans a variable segment of MOMP and is likely a serovar E-specific epitope. The other four epitopes are localized in constant segments and are C. trachomatis species specific. CTL populations specific for one or more of the four constant segment epitopes were isolated from all 10 infected subjects tested, regardless of infecting serovars, but from only one of seven uninfected subjects tested. The CTLs failed to recognize corresponding peptides derived from Chlamydia pneumoniae MOMP, further suggesting that they indeed resulted from genital tract infections with C. trachomatis. Significantly, ME180 human cervical epithelial cells productively infected with C. trachomatis were killed by the MOMP peptide-specific CTLs. Further investigations of the ability of such CTLs to lyse normal infected epithelial cells and their presence at inflamed sites in the genital tract will help understand the protective or pathological role of CTLs in chlamydial infections. The MOMP CTL epitopes may be explored as potential components of a subunit vaccine against sexually transmitted diseases caused by C. trachomatis. Moreover, the knowledge provided here will facilitate studies of HLA class I pathways of chlamydial Ag processing and presentation in physiologically relevant human APCs.

Background: To evaluate the changes occurring in the somatic innervation throughout the levator ani muscle in women with genitourinary prolapse and stress urinary incontinence (SUI)., Methods: Thirty-four patients with genital prolapse entered the study and ten subjects with non-malignant pathologies acted as a control group. All patients were evaluated by urodynamic investigation and an electromyographic study of pelvic floor muscles to define the type of urinary incontinence. Biopsy samples were obtained from both groups of patients: the site of muscle biopsies were left and right part of perirectal pubococcygeus muscle. The evaluation of immunoreactivity was semiquantitative and based on staining intensity and distribution., Results: In all cases, S-100 protein and NSE immunoreactivities were found in nerve fascicles running throughout the striated muscle. NPY and VIP positivities were more intense and diffuse, whereas SP immunoreactivity was quite scanty. The different patterns of NPY and VIP expression changed in relation to degree of genital prolapse and to the presence of SUI., Conclusions: Our immunohistochemical study shows the presence in the pelvic floor of neurons that are able to synthesize neuropeptides. The lower immunoreactivity score of same neuropeptides (VIP, NPY) observed among patients with third degree genital prolapse and with SUI could be related to biochemical damage of the neurons with subsequent lower production of chemical messengers.

Mucosal epithelial cells contribute significantly to host defense mechanisms. Uroepithelial cells (UEC) from healthy donors suppress bacterial growth in vitro. Bacterial adherence to UEC has been shown to be a prerequisite. Similar results have been shown for buccal epithelial cells (BEC). The host response triggered by the host-parasite interaction seems to involve signal transduction and intracellular activation of second messengers. In this study the intraepithelial calcium flux was analyzed in individual BEC after bacterial contact. BEC were derived from scrapes of the buccal mucosa and labelled with fluo-3 (a calcium indicator). Thereafter the cells were analyzed immediately with a FACscan flowcytometer. The intracellular events were evaluated before and after the addition of viable E. coli bacteria (strain 4389, K1O1H7, pili II pos.). For control, the influence of prostaglandins, histamine, PMA, LPS and opsonized avital E. coli on the epithelial calcium flux was investigated. Additionally, supernatants of BEC-E. coli cocultures were analyzed with respect to their PgE2 content. PgE2 concentrations in supernatants of BEC, cultured alone or together with E. coli, were measured by a commercial PgE2 ELISA kit. The addition of vital E. coli to BEC was promptly answered by a significant intracellular calcium flux. PgE2, histamine and PMA, but not PgF2alpha, PgE1, LPS and opsonized E. coli, increased intracellular calcium. BEC alone did not release PgE2. After coculture with E. coli increased levels of PgE2 were measured in the supernatants. PgE2 release was still enhanced by coactivation of the BEC with phorbolester (PMA). Our results confirm that calcium flux in mucosal epithelial cells is stimulated by the cell-bacteria contact. We suggest that the increased PgE2 release amplifies the stimulation of intraepithelial second messengers. The resulting cell activation may lead to the secretion of antimicrobial peptides, thereby contributing to the regulation of mucosal host resistance to bacterial infections.

The comparative study of the main characteristics of immune status in patients with urogenital chlamydiosis, furunculosis, urogenital herpes (38 patients) and in the members of the control group (21 subjects) was made. The analysis of the results obtained in this study revealed the numerical values of immunological characteristics, capable of being used as markers indicating transition into the chronic form. Thus, it showed a decrease in the population of cells with phenotype CD72+ in chlamydiosis; a fourfold increase in the population of cells with phenotype CD16+ in furunculosis; an increase in the population of cells with phenotype CD8+, a decrease in the immunoregulatory index and the population of cells with phenotype CD72+ in herpes. The data thus obtained may be used in prescribing immunocorrective therapy.

The possible connection of viruses with tumours was investigated by serologic examinations. Concerning the presence of antibodies against adenoviruses, especially those against the early non-virion antigens of oncogenic adenovirus type 12, approximately 4000 tests were made with sera of 446 urogenital patients with and without tumours and 70 ones with internal diseases. It was found by complement fixation tests that antibodies against nonvirion antigens of adenoviruses were present in 53% of urogenital patients suffering from malignant tumours and prostatic hypertrophy, in 18% of non-tumourous urological patients and in 4% of patients with internal diseases, respectively. The results suggest that adenoviruses may play a role in tumourous diseases of the urogenital organs.

Spermatozoa are immunogenic and may induce an immune response in reproductive compartments. There have been controversies concerning the effect of naturally existing antisperm antibodies on fertility of males and females. It is known, that men or women suffering from unexplained infertility have often antisperm antibodies in their urogenital secretions and/or serum. Systemic and local immune responses to sperm antigens differ between each other and they may differently affect the fertilisation process. Physiologically, females are protected from an immune response against "foreign", spermatozoal antigens. Nevertheless under local pathological conditions antisperm antibodies can be induced and may interfere with fertilisation.

Infection with Chlamydia trachomatis results in the formation of a variety of antibodies with group, species, subspecies and serovarspecificity. Sera from patients with genital tract infections often show broad reactivity in serological tests. This may be due to the presence of cross-reacting antibodies, repeated infections by different serotypes or concurrent genital and respiratory infections by different chlamydial species. Other factors contributing to difficulties in interpretation include how antibody titres in acute mucosal infections, the occurrence of latent infections and reactivations, and the persistence of IgG which does not allow the differentiation of past from current infections. For these reasons, serology alone is inadequate for the diagnosis of uncomplicated lower genital tract infections. In upper genital tract infections, however, because of difficulties with sampling from the infected site, a positive serology may be the only indications of chlamydial involvement. This paper discusses the principles of chlamydial antibody assays, difficulties with their interpretation and their role in the diagnosis of upper and lower genital tract infections.

We evaluated the Syva MicroTrak Chlamydia Blocking Antibody Assay as a confirmatory assay for the detection of Chlamydia trachomatis in urogenital specimens. During a 5-month period, 109 positives were obtained (4.9%) by the MicroTrak II Enzyme Immunoassay as implemented with the Syva XL automated enzyme immunoassay instrument. Of 98 evaluable samples, 92 (93.9%) were confirmed as positive by the blocking assay, and 3 blocking-negative samples had organisms detected by direct fluorescent-antibody analysis (blocking sensitivity, 96.8%). We found that direct fluorescent-antibody analysis of samples with a specimen-to-cutoff absorbance ratio of < or = 2.0 was a reasonable confirmation alternative and was more cost-effective than the blocking assay.

Objectives: To evaluate whether Chlamydia-infected patients with and without urogenital symptoms have similar rheumatological manifestations or whether they belong to distinct clinical groups., Methods: In a university-based study, we examined patients with unexplained arthritis in whom other rheumatic diseases had been excluded for urogenital chlamydial infection, and we investigated the clinical and radiological manifestations of the Chlamydia-positive patients., Results: Sixty of 283 patients (21%) with unexplained arthritis had urogenital chlamydial infection. The infection was asymptomatic in 30%. There was no difference in the pattern of arthritis or immunological and serological characteristics in the patients with and without symptoms of urogenital infection, respectively., Conclusion: The pattern of Chlamydia-induced arthritis is similar in patients with or without symptoms of urogenital chlamydial infection. To recognize CIA, it may be helpful to examine patients with unexplained arthritis for Chlamydia even though they do not have symptoms of urogenital infection.

Objective: To study: (a) the chlamydial antibody response (to the D-K serovars) using the micro-immunofluorescence (micro-IF) test in the following groups: (I) chlamydial genital infection only, (II) chlamydial ocular infection only, (III) combined chlamydial ocular and genital infection (oculo-genital infection), (IV) chlamydial ocular infection with chlamydia-negative non-gonococcal urethritis, (V) adenovirus conjunctivitis (control group 1), (VI) male partners of group I-IV with no chlamydial oculogenital infection or non-gonococcal urethritis (control group 2) (b) the cross reactivity of antibodies in patients' sera between the three chlamydial species and within the serovars of C trachomatis in those with culture-positive chlamydial oculo-genital infection., Setting: oculogenital (diagnostic) clinic at Moorfields Eye Hospital, London, UK., Subjects: 209 consecutive patients attending the clinic with Chlamydia trachomatis oculogenital infection and 86 patients with adenovirus conjunctivitis (control group 1) and 55 male partners with no evidence of chlamydial oculogenital infection or non-gonococcal urethritis (control group 2)., Results: Of all the patients with proven chlamydial oculogenital infection, 10.5% (22/209) and 94% (197/209) had IgM and IgG antibodies respectively. The geometric mean IgG antibody titres (GMT) were 1:98, 1:123, 1:245 and 1:101 in groups I to IV respectively. The IgG GMT values seen in control groups 1 and 2 were 1:45 and 1:36 respectively. Only 2/86(2%) patients in group V (control group 1) had IgG chlamydial antibodies of 1:32 and 1:64, whilst only 1/55(1.8%) and 4/55(7.3%) of patients in group VI(control group 2) had chlamydial IgG antibody titres of > or = 1:256 and > or = 1:128 respectively. A four-fold rise or fall in IgG antibody titre occurred in 56%(107/192) of patient groups I-IV over 2-6 weeks. Low titre cross-reactive antibody responses against different chlamydial species and serovars were commonly seen; 71%(148/209) of all patients showed cross-reactivity with Chlamydia pneumoniae or psittaci species or both, whilst 92% (193/209) of patients showed some level of cross reactivity to other pooled serovars of C trachomatis (A-C and L 1-3)., Conclusions: Serological diagnosis of chlamydial infection as evidenced by a positive IgM antibody response, high IgG titre (> or = 1:256) or > or = 4-fold rise or fall in IgG antibody titre was seen in 78%(163/209) of patients with culture-positive chlamydial oculogenital infection. Chlamydial IgG antibody titres of > or = 1:256 had a sensitivity of 42.6%, specificity of 98.2%, positive predictive value of 98.8% and a negative predictive value of 31% for chlamydial infection at any site, when considering groups I-IV and control group 2. In this study of 216 patients with conjunctivitis, a positive IgG antibody response (titre > or = 1:16) had a sensitivity of 98.5%, specificity of 97.7%, positive predictive value of 98.5% and a negative predictive value of 97.7%, for chlamydial conjunctivitis. Patients with dual chlamydial infection of conjunctiva and genital tract had a higher IgG GMT titre than those with ocular or genital infection alone: infection at a second site may produce an anamnestic response. Although the micro-IF test is a useful adjunct for the diagnosis of chlamydial infection, cross-reactivity between different chlamydial species and serovars is common. Chlamydial seroepidemiological studies should be interpreted with caution, as studies may attribute a serological response to a particular species or serovar in a setting where two or more are prevalent.

Seven cases of genito-urinary malacoplakia were analyzed histologically, ultrastructurally and immunohistochemically in a comparison with two cases of xanthogranulomatous pyelonephritis. Immunohistochemically, von Hansemann cells and Michaelis-Guttmann bodies, both hallmarks for the diagnosis of malacoplakia, showed a common antigenicity for enteropathogenic Escherichia coli as cytoplasmic granules of varying sizes. These microscopic manifestations corresponded ultrastructurally to a series of phagolysosomal degradations of coliform bacilli. Serogroups against E. coli OK antigens, which were positive for malacoplakic cells, were not confined to a particular group. Macrophages of xanthogranulomatous pyelonephritis did not show the E. coli antigenicity. Antigenicity of lysozyme and alpha-1-antichymotrypsin on the von Hansemann cells was equivocal, but these enzymes were strongly positive on macrophages of xanthogranulomatous pyelonephritis. The macrophages of both malacoplakia and xanthogranulomatous pyelonephritis were positive for antihuman macrophage antibody. These results indicate that malacoplakia depends mainly on infection by a non-specific strain of enteropathogenic E. coli and may arise from defective digestive enzyme activity of infiltrating macrophages. Immunohistochemical analysis using antisera against E. coli OK antigens, lysozyme and alpha-1-antichymotrypsin was useful in identifying the prediagnostic stage of malacoplakia and in differentiating the lesion from xanthogranulomatous pyelonephritis.

A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50-79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non-reactive with antibodies to serum amyloid A protein, prealbumin and beta 2 microglobulin, while equivocal immunoreactivity was seen with anti-light chain antibodies.

IgA antibody titers to C. trachomatis in local secretions were measured by immunoperoxidase assay (Savyon kit) in male and female cases with various urogenital infections, and the clinical significance of IgA antibody in the local secretion was discussed. In addition, the antigen specificity of the IgA for C. trachomatis in the local secretions was analyzed by immunoblotting assay. 1) In female cases with cervicitis and male cases with urethritis, the positive rate of IgA antibody in their secretions was higher in cases with C. trachomatis antigen than in those without it. In addition, the IgA antibody titers in their secretions tended to be higher than in serum, suggesting that the result reflected a local immune response at the site of infection. 2) In cases with chronic prostatitis, a condition in which detection of antigen at the site of infection was difficult, the positive rate of IgA antibody in prostatic secretion was 23.6%. We confirmed that most of the IgA antibodies in prostatic secretions were of the secretory type. 3) IgA antibodies in secretions reacted to the major outer membrane protein (MOMP) and 60-Kd polypeptides of the outer membrane of C. trachomatis by immunoblotting assay, proving that they were the secretory IgA antibodies specific for C. trachomatis. These results described above confirmed that measurement of IgA antibody titers in local secretions by immunoperoxidase assay and immunoblotting assay was useful for the diagnosis of chlamydial urogenital infections such as chronic prostatitis, which the antigen detection was usually difficult. Examination of IgA antibody in local secretions was considered to be useful for making a correct diagnosis even in cases who were suspected to have C. trachomatis infection but showed negative antigen.

The results of the analysis of the cell-mediated and humoral factors of the peripheral blood and cervical mucus in pregnant women with urogenital infections (pyelonephritis, colpitis, cervicitis, endocervicitis) and in healthy pregnant women are presented. These results indicate that considerable changes in the systemic immunity of the body and in the local antiinfectious protection of the reproductive tract develop in pregnant women with urogenital infections. The prescription of bifidumbacterin and lactobacterin to the patients during pregnancy (intravaginally) and bemitil after parturition (orally) completely restores the functional validity of their immune system and decreases the number of postnatal complications.