Immunoglobulin G4-related Disease of the Genitourinary System: Spectrum of Imaging Findings and Clinical-Pathologic Features.

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.

Imaging features of immune-mediated genitourinary disease.

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.

Exploiting ovine immunology to improve the relevance of biomedical models.

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.

[SPECIES COMPOSITION OF INFECTIOUS FACTORS THAT CAUSE THE REACTIVE ARTHRITIS DEVELOPMENT AND THEIR EFFECT ON ARGINASE-NO-SYNTHASE REGULATORY SYSTEM OF PERIPHERAL BLOOD LYMPHOCYTES].

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.

Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.

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.

Immunity in urogenital protozoa.

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.

[The comparative characteristic of immune status of males with bacterial inflammatory urogenital pathology of different etiology in the city of Orenburg].

The article discusses presence of typical characteristics of parameters of system immunity under gonococcal and nonspecific uretroprostatitis and diagnostic value of these indicators. The reliable differences of immunologic indicators in patients with gonorrhea are established as compared to patients with nonspecific bacterial uretroprostatitis. The study established in peripheral blood the reliable decrease of level of leukocytes, relative amount of monocytes, phagocyte index, functional reserve of leukocytes at the expense of spontaneous and stimulated NBT test, IgA, sIgA. On the contrary, the study detected increasing of level of IgM and lactoferrin in patients with gonorrhea as compared to corresponding indicators in patients nonspecific infections. Under gonorrhea, the largest deviation of indicators from standard values was established for lactoferrin. The detected differences of immunologic parameters can be used as differentiating markers of nonspecific and gonococcal uretroprostatitis and criteria of effectiveness of immune correction.

The spectrum of IgG4-related disease in the abdomen and pelvis.

OBJECTIVE: IgG4-related disease was not recognized as a specific clinical entity until 2003 when extrapancreatic lesions were reported in patients with autoimmune pancreatitis. IgG4-related disease is characterized by elevated serum IgG4 levels and infiltration of the target organ by IgG4-positive plasma cells. The complete gamut of visceral involvement is still being outlined. The purpose of this article is to highlight the plethora of lesions under the spectrum of IgG4-related disease of the abdomen and pelvis, describe their imaging appearances on multimodality cross-sectional imaging, and discuss the differential diagnoses. CONCLUSION: It is important for radiologists to recognize the multiorgan involvement and few classic features of IgG4-related disease that often tend to simulate malignancy.

[Seminal cytokines: is quantification useful in urogenital disorders?]. / Zytokine im Ejakulat : Ist die Bestimmung bei urogenitalen Erkrankungen sinnvoll?

Cytokines are cellular messengers which play a key role in many biological conditions such as immune defence and reproduction. During recent years analysis of seminal cytokines has become of increasing interest in various pathologies. To evaluate the current role of seminal cytokines we performed a systematic literature search within the framework of our focus group "Male Infertility during Infection and Inflammation - MIBIE". Out of 581 manuscripts we identified 124 original articles which investigated a total of 31 different cytokines. These studies can be categorized according to the following three topics: infertility, infections and chronic prostatitis. The current analysis demonstrates that seminal cytokine profiles are not associated with either semen quality or fertility; however, cytokines might be beneficial for diagnosis and monitoring therapy in patients with urogenital infections/inflammation. Further studies are needed to clarify if a single cytokine or a combination of different cytokines is necessary to evaluate different pathologies.

[Influence of immunocorrection on the inflammatory process in the urogenital tract in men with infertility].

We studied the concentration of metalloproteinases, pro-and anti-inflammatory cytokines, lymphocyte activation markers in seminal plasma of men with oligosymptomatic forms of chronic inflammation of the urogenital tract complicated with infertility. It was shown that chronic inflammation of the urogenital tract shifts the levels of cytokine profile, reduces the concentration of metalloproteinase-2 (576.4 +/- 89.3 ng/ml, P < 0.001), chemokines - fractalkine (16.3 +/- 1.3 pg/ml, P < 0.001) and chemmmokine regulated by activation, expression and secretion of normal T-cells (RANTES (12.7 +/- 1.0 pg/ ml, P < 0.001). Additionally, we observed a sharp increase in IL-8 (215.5 +/- 7.8 pg/ml, P < 0.01), MCP-1 (926.4 +/- 30.2 pg/ml, P < 0.001) and elevation of the CD25 + / CD95 + ratio. These observations point for alterations in apoptotic mechanisms in pathological forms of the generative cells and their accumulation in the sperm. Prolonged inflammation of the genital area is accompanied by depletion of the local immune system resulting in the development of infertility. The multidirectional shifts in IL-10/IL-12 index have been established: an increase in the group of patients with elevated level of hypercapitated spermatozoa and its reduction in microsomatic morphotype of spermatozoa. These data emphasize the importance of the microenvironment in maturation of gametes. It was shown that an inclusion of alfagin and gepatomax in immunorehabilitation of men with oligosymptomatic forms of urogenital infections improves leukocyte subpopulation content of sperm and concentrations of pro-and anti-inflammatory cytokines, and therefore, results in an increase in fertilizing potential.

[Influence of phytotherapy on pro- and antioxidant status in spermatozoa, seminal plasma and immunologic status of sperm in men with chronic inflammation of the urogenital tract complicated by infertility].

The lipid peroxidation and antioxidant enzymes in the blood of men with oligosymptomatic forms of chronic inflammation of the urogenital tract complicated by infertility are studied. Studied cytokine status of sperm in infertile men. The positive effect of imupret in combination with gepatomax on the oxidative activity systems, which leads to an improvement of leukocyte subpopulations of sperm, to normalize the concentrations of pro- and anti-inflammatory cytokines, and therefore, an increase in fertilizing are shown.

Male rodent genital tract infection with Chlamydia muridarum: persistence in the prostate gland that triggers self-immune reactions in genetically susceptible hosts.

PURPOSE: We investigated Chlamydia trachomatis infection and its pathogenic consequences in the male rodent genital tract. MATERIALS AND METHODS: Male rats were inoculated in the meatal urethra with Chlamydia muridarum. We sought bacterial DNA at early and late times after inoculation in different parts of the male genital tract. Histological alterations and the immune response against prostate antigens were analyzed. RESULTS: Male rats showed ascending infection with wide dissemination of bacteria in the genital tract at an early time point after inoculation. At later stages bacteria persisted only in some parts of the genital tract and in the prostate gland. C. muridarum was also detected in semen in a high proportion of rats irrespective of an acute or chronic stage of infection. Histological alterations that accompanied C. muridarum were especially observed in the prostate and mainly composed of CD3+ cell infiltration. Positive humoral and cellular responses against prostate antigens were noted in a considerable number of infected rats. NOD mice, an autoimmune, prostatitis prone strain, showed a similar pattern with C. muridarum in the prostate of 100% of infected mice, which was again accompanied by mononuclear cell infiltration and antibodies against prostate antigens at early and late times after inoculation. CONCLUSIONS: Results reveal that C. muridarum infects the male rodent genitourinary tract with special persistence in the prostate gland, where it causes chronic inflammation that in turn may act as a trigger factor for self-immune reactions in susceptible hosts.

Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study.

BACKGROUND: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk. METHODS: A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. RESULTS: PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305). CONCLUSIONS: Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.

[Diagnostic value of seminal bactericidal activity in bacteria carriers].

Seminal bactericidal activity (SBA) that is referred to as a factor of natural resistance and that controls bacterial survival in the male urogenital tract is an integral index of the congenital adaptive mechanisms of mucosal defense. The paper shows changes in SBA and other indices of the functional activity of the reproductive tract in male patients with different forms of bacteria carriage.

[Comparative efficiency of detection of the causative agent of urogenital chlamydiasis by immunofluorescence, polymerase chain reaction, and dot immunoassay].

The diagnostic efficiency of three diagnostic kits--two commercial (for direct immunofluorescent test (DIFT) and polymerase chain reaction (PCR) and one predeveloped experimental dot-ELISA--was compared. For this, specimens (cervical or urethral scrapes) from 225 patients with suspected or verified urogenital chlamydiasis were analyzed. Dot-ELISA was shown to have a higher sensitivity and a higher specificity than both commercial kits. The coincidence of positive and negative results of dot-ELISA with DIFT and PCR was 98.6 +/- 1.4 and 100%, respectively. In addition, dot-ELISA on the "Amersham" membrane could detect cases of the disease by 7 and 1.2 times, as compared with PCR and DIFT, respectively. The prospects of the dot-ELISA kit for the rapid, simple, and cheap diagnosis of urogenital chlamydiasis are discussed.