Immunopathological Features Research Articles

Immunopathological Features Developing in the Mosquito Midgut after Feeding on Anopheles gambiae Mucin-1 / Interleukin-12 cDNA Immunized Mice

El intestino medio es el organo al cual pasa la sangre consumida por el mosquito y donde, mediante una membrana peritrofica secretada por el epitelio, esta sangre es mantenida durante la digestion y absorcion. El intestino del mosquito esta revestido por microvellosidades llenas de actina que son expuestas a las complejas condiciones en torno a la luz intestinal, tales como la abrasion producida por particulas de alimentos, hidrolasas digestivas y el ataque de patogenos y parasitos que son tomados en la sangre consumida. Estas microvellosidades se protegen de estos efectos mediante la matriz peritrofica, el glicocalix y las proteinas de mucina que revisten las superficies epiteliales. La inmunizacion con AgMUC1/IL-12 ADNc en ratones BALB/c ha demostrado ser util para matar los mosquitos cuando se alimentan de estos ratones. La mucina es una de las proteinas producidas en el intestino medio del mosquito despues de consumir sangre. La fina estructura del epitelio del intestino interactua con factores inmunes tales como anticuerpos o celulas inmunes es de especial importancia para interpretar los eventos tempranos en la interaccion entre el revestimiento del intestino medio y los componentes inmunologicos especificos presentes en la sangre de ratones BALB/c inmunizados con AgMUC1/IL-12 cDNA. Despues de observar mediante microscopias de luz, electronica de barrido y de transmision las caracteristicas de secciones del intestino medio del mosquito Anopheles gambiae alimentado de ratones BALB/c inmunizados con AgMUC1/IL-12 cDNA, mecanismos inmunes mediados por citotoxicidad celular dependiente de anticuerpos (ADCC) podrian ser los responsables de matar a los mosquitos. Los procesos necroticos y apoptoticos que pueden ser la causa de la muerte del mosquito tienen lugar en las celulas que recubren el epitelio del intestino medio.

Type II collagen–specific antibodies induce cartilage damage in mice independent of inflammation

Murine collagen antibody-induced arthritis (CAIA), like collagen-induced arthritis, has clinical and immunopathologic features that parallel those in human rheumatoid arthritis (RA). This study was undertaken to examine the effects of autoantibodies to type II collagen (CII) on articular cartilage in the paws of mice, under conditions in which other factors that may influence joint pathology could be excluded. Mice of 2 different strains, B10.QC5δ and the parental strain B10.Q, were injected intravenously with either saline or arthritogenic monoclonal antibodies (mAb) to CII. B10.QC5δ mice lack complement factor C5 and do not develop CAIA when injected with arthritogenic mAb, whereas B10.Q mice have C5 and develop CAIA when administered the mAb and a subsequent injection of lipopolysaccharide. Three days after injection the paws of the mice were examined by standard histologic methods to assess morphologic appearance and proteoglycan loss, and by synchrotron-enhanced Fourier transform infrared microspectroscopy to assess chemical evidence of structural change. No macroscopic or microscopic signs of inflammation were evident in the mice. However, in contrast to the saline-injected controls, all mAb-injected mice exhibited cartilage damage in all joints, with loss of proteoglycans and collagen, chondrocyte hyperplasia and/or loss, and surface damage in the interphalangeal joints. The implication of these findings is that an autoimmune response to CII can disrupt articular cartilage, particularly that of the small joints, and the subsequent integrity of the cartilage depends on a balance between breakdown and repair. This has relevance with regard to RA, in which such autoantibodies occur but the inflammatory response may dominate clinically and mask underlying features of the autoimmune response.

Clinical and immunopathological features of patients with lupus hepatitis

Background Lupus hepatitis is yet to be characterized based on its clinical features and is often difficult to differentially diagnose from other liver diseases. We aimed to elucidate clinical, histopathological and immunopathological features of lupus hepatitis and to evaluate primarily the effectiveness of liver immunopathological manifestations on differential diagnosis of lupus hepatitis from other liver diseases. Methods A retrospective study was performed to analyze clinical features of lupus hepatitis in 47 patients out of 504 inpatients with systemic lupus erythematosus (SLE) in First Affiliated Hospital of Sun Yat-sen University, China from May 2006 to July 2009, and to evaluate the association between lupus hepatitis and SLE activity. Additionally, liver histopathological changes by hematoxylin and eosin (HE) staining and immunopathological changes by direct immunofluorescence test in 10 lupus hepatitis cases were analyzed and compared to those in 16 patients with other liver diseases in a prospective study. Results Of 504 SLE patients, 47 patients (9.3%) were diagnosed to have lupus hepatitis. The prevalence of lupus hepatitis in patients with active SLE was higher than that in those with inactive SLE (11.8% vs. 3.2%, P <0.05). The incidence of hematological abnormalities in patients with lupus hepatitis was higher than that in those without lupus hepatitis (40.4% vs. 21.7%, P <0.05), such as leucocytes count (2.92×109/L vs. 5.48×109/L), platelets count (151×109/L vs. 190×109/L), serum C3 and C4 (0.34 g/L vs. 0.53 g/L; 0.06 g/L vs. 0.09 g/L) (P <0.05); 45 of 47 (95.7%) lupus hepatitis patients showed 1 upper limit of normal (ULN) <serum ALT level <5 ULN. The liver histopathological features in patients with lupus hepatitis were miscellaneous and non-specific, similar to those in other liver diseases, but liver immunopathological features showed positive intense deposits of complement 1q in 7/10 patients with lupus hepatitis and negative complement 1q deposits in all patients with other liver diseases (Fisher's exact test, P=0.011). Conclusions Lupus hepatitis was not infrequent in active SLE patients which would be one of the indices indicating SLE activity. Positive intense deposit of complement 1q in liver may be a characteristic immunopathological feature of lupus hepatitis, which provides a new way to differentially diagnose lupus hepatitis from other liver diseases. Chin Med J 2013;126 (2): 260-266

Use of Mesenchymal Stem Cells (MSC) in Chronic Inflammatory Fistulizing and Fibrotic Diseases: a Comprehensive Review

Mesenchymal stem cells (MSC), multipotent adult stem cells, feature the potential to regenerate tissue damage and, in parallel, inhibit inflammation and fibrosis. MSC can be safely transplanted in autologous and allogeneic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, and 22 are on autoimmune diseases. In irradiation-induced colitis, MSC accelerate functional recovery of the intestine and dampen the systemic inflammatory response. In order to provide rescue therapy for accidentally over-irradiated prostate cancer patients who underwent radiotherapy, allogeneic bone marrow-derived MSC from family donors were intravenously infused to three patients with refractory and fistulizing colitis resembling fistulizing Crohn's disease. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhoea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets towards an increase of T regulatory cells and a decrease of activated effector T cells. The current data indicate that MSC represent a promising alternative strategy in the treatment of various immune-mediated diseases. Encouraging results have already been obtained from clinical trials in Crohn's disease and SLE as well as from case series in systemic sclerosis. MSC represent a safe therapeutic measure for patients who suffer from chronic and fistulizing colitis. These findings are instructional for the management of refractory inflammatory bowel diseases that are characterized by similar clinical and immunopathological features.

Rhinitis, sinusitis and ocular disease – 2087. Usefulness of impulse oscilometry and fractional exhaled nitric oxide in children with eosinophilic bronchitis

Background Eosinophilic bronchitis (EB) is a common cause of chronic cough. Although EB shares many immunopathologic features with asthma, it does not show airway hyperresponsiveness or reversible airway obstruction by spirometry. Compared to healthy children without pulmonary disease, we hypothesized that EB patients would demonstrate abnormal pulmonary function and inflammation with impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO), which are more sensitive tests of these parameters than spirometry.

Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice

BackgroundBullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times.MethodsRabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice.ResultsCollagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies.ConclusionThis novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.

Expression of Suppressor of Cytokine Signalling proteins (SOCS) 1 and 3 in Beh�et�s Disease

Expression of Suppressor of Cytokine Signalling proteins (SOCS) 1 and 3 in Beh�et�s Disease

Clinical and immunological profile of umbilical involvement in pemphigus vulgaris and pemphigus foliaceus

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune vesicobullous disorders with IgG autoantibodies directed against desmoglein (Dsg)1 and 3, which lead to intraepidermal acantholysis. To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement. In total, 10 patients (7 women, 3 men; age range 24-70 years, disease duration 3-16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings [direct and indirect immunofluorescence (DIF and IIF) and ELISA with recombinant Dsg1 and Dsg3]. Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24-266 in PF and 0-270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22-98) and was negative in all PF sera. All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical-cord region.

Granulocyte-dependent Autoantibody-induced Skin Blistering

Autoimmune phenomena occur in healthy individuals, but when self-tolerance fails, the autoimmune response may result in specific pathology. According to Witebsky's postulates, one of the criteria in diagnosing a disease as autoimmune is the reproduction of the disease in experimental animals by the passive transfer of autoantibodies. For epidermolysis bullosa acquisita (EBA), a prototypic organ-specific autoimmune disease of skin and mucous membranes, several experimental models were recently established. In the animal model described in our present work, purified IgG antibodies against a stretch of 200 amino acids (aa 757-967) of collagen VII are injected repeatedly into mice reproducing the blistering phenotype as well as the histo- and immunopathological features characteristic to human EBA 1. Full-blown widespread disease is usually seen 5-6 days after the first injection and the extent of the disease correlates with the dose of the administered collagen VII-specific IgG. The tissue damage (blister formation) in the experimental EBA is depending on the recruitment and activation of granulocytes by tissue-bound autoantibodies 2,-4. Therefore, this model allows for the dissection of the granulocyte-dependent inflammatory pathway involved in the autoimmune tissue damage, as the model reproduces only the T cell-independent phase of the efferent autoimmune response. Furthermore, its value is underlined by a number of studies demonstrating the blister-inducing potential of autoantibodies in vivo and investigating the mechanism of the blister formation in EBA 1,3,-6. Finally, this model will greatly facilitate the development of new anti-inflammatory therapies in autoantibody-induced diseases. Overall, the passive transfer animal model of EBA is an accessible and instructive disease model and will help researchers to analyze not only EBA pathogenesis but to answer fundamental biologically and clinically essential autoimmunity questions.

Granulocyte-dependent Autoantibody-induced Skin Blistering

Autoimmune phenomena occur in healthy individuals, but when self-tolerance fails, the autoimmune response may result in specific pathology. According to Witebsky's postulates, one of the criteria in diagnosing a disease as autoimmune is the reproduction of the disease in experimental animals by the passive transfer of autoantibodies. For epidermolysis bullosa acquisita (EBA), a prototypic organ-specific autoimmune disease of skin and mucous membranes, several experimental models were recently established. In the animal model described in our present work, purified IgG antibodies against a stretch of 200 amino acids (aa 757-967) of collagen VII are injected repeatedly into mice reproducing the blistering phenotype as well as the histo- and immunopathological features characteristic to human EBA (1). Full-blown widespread disease is usually seen 5-6 days after the first injection and the extent of the disease correlates with the dose of the administered collagen VII-specific IgG. The tissue damage (blister formation) in the experimental EBA is depending on the recruitment and activation of granulocytes by tissue-bound autoantibodies (2,-4). Therefore, this model allows for the dissection of the granulocyte-dependent inflammatory pathway involved in the autoimmune tissue damage, as the model reproduces only the T cell-independent phase of the efferent autoimmune response. Furthermore, its value is underlined by a number of studies demonstrating the blister-inducing potential of autoantibodies in vivo and investigating the mechanism of the blister formation in EBA (1,3,-6). Finally, this model will greatly facilitate the development of new anti-inflammatory therapies in autoantibody-induced diseases. Overall, the passive transfer animal model of EBA is an accessible and instructive disease model and will help researchers to analyze not only EBA pathogenesis but to answer fundamental biologically and clinically essential autoimmunity questions.

Retrospective analysis of 12 Korean patients with paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a rare, life-threatening, autoimmune, mucocutaneous blistering disease associated with neoplasia. Both humoral and cellular immunity are involved in the pathogenesis of PNP. Characteristically, PNP has a diverse spectrum of clinical and immunopathological features. We retrospectively analyzed 12 Korean patients with PNP who were diagnosed between 1993 and 2011. We performed analysis of the clinical features, clinical outcomes, underlying neoplasia, histological features and laboratory findings. All of the patients except one had severe mucosal involvement. Two patients had only mucosal lesions but no cutaneous involvement was observed. Erythema multiforme or lichen planus-like eruptions rather than bullous lesions were more commonly observed skin rashes. The most common histological features were interface dermatitis and apoptotic keratinocytes. There were associated hematological-related neoplasms in 11 patients, with Castleman's disease (n=4) as the most frequent. Twelve patients were followed for 5-148months (mean, 43.0). The prognosis depended on the nature of the underlying neoplasm. Six patients died due to respiratory failure (n=3), postoperative septicemia (n=1), lymphoma (n=1) and sarcomatosis (n=1). The 2-year survival rate was 50.0%, and the median survival period after diagnosis was 21.0months. Immunoblotting was performed in 12 patients and autoantibodies to plakins were detected in 11 patients. The results of this study demonstrated the clinical, histological and immunological diversity of PNP. Widely accepted diagnostic criteria that account for the diversity of PNP are needed.

Brucella abortus–Infected Macrophages Modulate T Lymphocytes to Promote Osteoclastogenesis via IL-17

The pathogenic mechanisms of bone loss caused by Brucella species have not been completely deciphered. Although T lymphocytes (LTs) are considered important to control infection, the mechanism of Brucella-induced T-cell responses to immunopathological features is not known. We present in vitro and in vivo evidence showing that Brucella abortus-induced inflammatory response leads to the activation of LTs, which further promote osteoclastogenesis. Pre-activated murine LTs treated with culture supernatant from macrophages infected with B. abortus induced bone marrow-derived monocytes (BMMs) to undergo osteoclastogenesis. Furthermore, osteoclastogenesis was mediated by CD4(+) T cells. Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. Neutralization experiments indicated that IL-6, generated by Brucella infection, induced the production of pro-osteoclastogenic IL-17 from LTs. By using BMMs from tumor necrosis factor receptor p55 knockout mice, we also demonstrated that IL-17 indirectly induced osteoclastogenesis through the induction of tumor necrosis factor-α from osteoclast precursors. Finally, extensive and widespread osteoclastogenesis was observed in the knee joints of mice injected with Brucella-activated T cells. Our results indicate that activated T cells, elicited by B. abortus-infected macrophages and influenced by the inflammatory milieu, promote the generation of osteoclasts, leading to bone loss.

Usefulness of impulse oscillometry and fractional exhaled nitric oxide in children with Eosinophilic bronchitis

Eosinophilic bronchitis (EB) is a common cause of chronic cough. Although EB shares many immunopathologic features with asthma, it does not show airway hyperresponsiveness or reversible airway obstruction by spirometry. Compared to healthy children without pulmonary disease, we hypothesized that EB patients would demonstrate abnormal pulmonary function and inflammation with impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO), which are more sensitive tests of these parameters than spirometry. A total of 232 children with asthma, 109 with EB, and 115 control subjects were enrolled. We compared pulmonary function parameters and FeNO levels among the three groups. Additionally, we designated a screening cutoff value of FeNO combined with IOS parameters to distinguish EB from the control group, and identify which children with EB have more asthmatic characteristics. By IOS, the bronchodilator response of the EB and asthma groups increased significantly compared to controls for both reactance at 5 Hz (Δ X5) and reactance area (Δ AX) (P < 0.0001). Cutoff values to distinguish EB from controls were a Δ X5 of -20% (sensitivity, 77.5%; specificity, 49.6%), and Δ AX of -30% (sensitivity, 75.0%; specificity, 46.0%), when the FeNO is 20 ppb. Reversible airway obstruction in IOS and elevated FeNO levels can be detected in children with EB. This would support that EB in children shows airway characteristics similar to those of asthma, and that a continuum exists between asthma and EB.

Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses

To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses. 10 client-owned horses with IMMK. Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained). Equine IgG, IgM, and IgA antibodies were used to detect corneal immunoglobulin via direct immunofluorescence (10 eyes). Serum and aqueous humor (AH) samples from 3 horses with IMMK were used to detect circulating and intraocular IgG against corneal antigens via indirect immunofluorescence on unaffected equine cornea. Percentage scores (scale, 0 to 4) of cells expressing CD3 (median, 2.35 [range, 0.2 to 3.7]; mean ± SD, 2.36 ± 1.08) were significantly greater than scores of cells expressing CD79a (median, 0.55 [range, 0 to 1.5]; mean, 0.69 ± 0.72). All samples stained positively for CD4- and CD8-expressing cells, with no significant difference in scoring. All samples stained positively for IgG, IgM, and IgA. No serum or AH samples collected from horses with IMMK reacted with unaffected equine cornea. Pathogenesis of superficial stromal IMMK included cell-mediated inflammation governed by both cytotoxic and helper T cells. Local immunoglobulins were present in affected corneas; however, corneal-binding immunoglobulins were not detected in the serum or AH from horses with IMMK.

Association between the subepidermal autoimmune blistering diseases linear IgA disease and the pemphigoid group and inflammatory bowel disease: two case reports and literature review

We report two patients with subepidermal autoimmune blistering diseases and inflammatory bowel disease (IBD) [one with linear IgA disease (LAD) and ulcerative colitis (UC), and the other with mucous membrane pemphigoid (MMP) and Crohn disease (CD)], and present a review of all previously reported cases. We reviewed the literature, and found 48 cases of patients with autoimmune blistering diseases and IBD. The blistering diseases were LAD (25 patients), bullous pemphigoid (BP) (21), MMP (1) and pemphigoid gestationis (1), while the IBD types comprised UC (40) and CD (8). We describe the clinical and immunopathological features and demographic characteristics of the patients. In all but one case, the diagnosis of IBD predated the development of the skin condition. The association was more common with LAD than BP. The immunopathogenesis of IBD and autoimmune blistering diseases is discussed and a link between them hypothesized, namely, that the presentation of multiple antigens to the immune system during the unregulated inflammation in the bowel wall results in excitation of the immune system and recognition of autologous antigens.

Clinical and Immunopathological Features of Moyamoya Disease

BackgroundMoyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis or occlusion of the terminal portion of internal carotid arteries and the formation of a vascular network at the base of the brain. The pathogenesis of MMD is still unclear.Methodology/Principal FindingsWe retrospectively analyzed clinical data for 65 consecutive patients with MMD in our institutions and evaluated the histopathological and immunohistochemical findings of intracranial vessels from 3 patients. The onset age distribution was found to have 1 peak at 40–49 year-old age group, no significant difference was observed in the female-to-male ratio (F/M = 1.2). Intracranial hemorrhage was the predominant disease type (75%). Positive family history was observed in 4.6% of patients. Histopathological findings were a narrowed lumen due to intimal fibrous thickening without significant inflammatory cell infiltration, and the internal elastic lamina was markedly tortuous and stratified. All 3 autopsy cases showed vacuolar degeneration in the cerebrovascular smooth muscle cells. Immunohistochemical study showed the migration of smooth muscle cells in the thickened intima, and aberrant expression of IgG and S100A4 protein in vascular smooth muscle cells. The Complement C3 immunoreactivity was negative.Conclusion/SignificanceThis study indicated that aberrant expression of IgG and S100A4 protein in intracranial vascular wall of MMD patients, which suggested that immune-related factors may be involved in the functional and morphological changes of smooth muscle cells, and finally caused the thickened intima. A possible mechanism is that deposits of IgG in the damaged internal elastic lamina may underlie the disruption of internal elastic lamina, which facilitated S100A4 positive SMCs migrated into intima through broken portions of the internal elastic lamina, resulting in lumen stenosis or occlusion, leading to compensatory small vessels proliferation.

IFN-γ–Driven IDO Production from Macrophages Protects IL-4Rα–Deficient Mice against Lethality during Schistosoma mansoni Infection

The balance between alternatively activated macrophages (AAMs)/M2 cells and classically activated macrophages (M1 cells) is largely dependent on the effects of IL-4 and interferon (IFN)-γ, respectively. Although AAM/M2 cells can suppress inflammation and repair damaged tissue, M1 cells produce an array of pro-inflammatory molecules. Macrophage effector functions are critical for host protection against many infectious diseases, but it remains unknown whether lethal immunopathological characteristics, caused by Schistosoma mansoni infection in IL-4 receptor α-deficient mice (IL-4Rα(-/-)), results from the absence of M2 cells or increased numbers of M1 cells. In this study, we generated mice that completely lack IL-4Rα signaling in the context of a macrophage-specific loss of IFN-γ responsiveness (MIIG × IL-4Rα(-/-)). Contrary to what we expected, acute schistosomiasis resulted in greater liver injury and mortality in MIIG × IL-4Rα(-/-) mice compared with IL-4Rα(-/-) mice. Greater tissue injury in MIIG × IL-4Rα(-/-) mice was likely because of a lack of indoleamine 2,3 dioxygenase (IDO), a critical regulator of immunosuppression. Indeed, MIIG × IL-4Rα(-/-) failed to up-regulate IDO expression, and IL-4Rα(-/-) mice treated with an IDO antagonist underwent greater liver damage and mortality compared with mock-treated IL-4Rα(-/-) mice. Thus, we propose that, in the absence of AAM/M2 cells, IFN-γ-induced M1 cells suppress tissue-damaging inflammation during acute schistosomiasis through an IDO-dependent mechanism.

Detection of herplex simplex virus-1 and -2 in cardiac myxomas.

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCR-Restriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P < 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences.

Glomerular diseases in the Military Hospital of Morocco: Review of a single centre renal biopsy database on adults

Epidemiological studies provide useful information for clinical practice and investigations. This report aimed to determine glomerular diseases frequencies in a region of Morocco. All native renal biopsies (January 2000 to December 2007) on adults were reviewed, but only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. We have performed 171 renal biopsies in 161 patients (101 males and 60 females), the mean age was (range) 40.4 ±15 years (16–72). Clinical indications that lead to renal biopsy were: nephrotic syndrome (60.3%), renal failure of unknown aetiology (31.6%), asymptomatic urinary abnormalities (6.2%) and nephritic syndrome(1.9%). Primary glomerular diseases were reported in 84 patients (52%). The most common histological lesion was minimal change disease (26%). Idiopathic membranous glomerulopathy was the second most common lesion (23%) followed by membranoproliferative glomerulonephritis (17%), IgA nephropathy (12%), focal and segmental glomerulosclerosis (9.4%) and crescentic glomerulonephritis (6%). Secondary glomerular diseases were reported in 53 patients (33%). Lupus nephritis was the secondary glomerular disease most frequent (45%) followed by amyloïdosis (19%), diabetic nephropathy (15%), and Good pasture's syndrome (7.6%). The most common complications of the procedure were pain at biopsy site in 4%, gross hematuria in 11.1%, perirenal hematoma in 5% and hematuria requiring nephrectomy in 0.6% patients. Minimal change disease was the most frequent primary glomerulopathy and lupus nephritis was the most frequent secondary glomerulopathy in our group. The reasons for these findings are unclear. This information is an important contribution to the understanding the prevalence of renal diseases in North Africa.

Evaluation of Clinical and Immunopathological Features of Different Infective Doses ofTrypanosoma cruziin Dogs during the Acute Phase

Infection with Trypanosoma cruzi is a major risk in Latin America, and dogs are believed to be good models for evaluating Chagas disease. Here, we evaluated the clinical and immunopathological alterations developed by mongrel dogs experimentally infected with different infective doses (2,000, 20,000, and 200,000 metacyclic trypomastigotes of Sylvio X10/4 strain kg−1 via intraperitoneal). Clinical and electrocardiographic parameters, as well as antibody production and pathologic lesions were evaluated. All three doses of this strain of T. cruzi induced a similar pattern of infection characterized by cardiac arrhythmias and severe and diffuse myocarditis. Specific anti-T. cruzi IgG indicated seroconversion by day 14 after infection, and IgG levels increased during the period of evaluation. Mortality was observed only in dogs infected with the medium or high parasite doses, but not in the group infected with a low dose of 2,000 parasites kg−1. Infection with a low dose of parasites provides an excellent nonlethal model to evaluate the immunopathology of the acute disease in dogs infected with the Sylvio X10/4 strain of T. cruzi.