Immunopathological Features Research Articles

Increase of high mobility group box chromosomal protein 1 in eosinophilic chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by eosinophil-dominant infiltration in Europe and the United States. However, CRSwNP in Asia has shown different immunopathologic features. High-mobility group protein box 1 (HMGB1) is a DNA-binding protein that has been suggested to be involved in various chronic inflammatory diseases. The objective of this study is to investigate whether HMGB1 is augmented in the Chinese eosinophilic CRSwNP and if non-eosinophilic CRSwNP is associated with interleukin 5 (IL-5), IL-8, and tumor necrosis factor α (TNF-α). Nasal polyps specimens were collected from 41 patients with CRSwNP (20 eosinophilic and 21 non-eosinophilic) undergoing functional endoscopic sinus surgery (FESS). Biopsies of uncinate process, and ethmoidal mucosa from 9 non-CRS patients were used as controls by means of immunohistochemistry (IHC) staining, Western blotting, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). HMGB1-positive expression was significantly increased in the epithelium and among the large inflammatory cells infiltration in Eos CRSwNP and non-Eos CRSwNP as compared with controls (p < 0.001). The HMGB1 protein and messenger RNA (mRNA) levels of HMGB1, IL-5, IL-8, and TNF-α were significantly higher in eosinophilic CRSwNP than those from controls and non-eosinophilic CRSwNP, but no significant differences in these markers were found between non-eosinophilic CRSwNP and controls. HMGB1 expression levels correlated significantly and positively with IL-5, IL-8, and TNF-α (rs = 0.665, 0.771, and 0.724, respectively; p < 0.001) and slightly with eosinophil infiltration (rs = 0.149; p = 0.012) and the blood eosinophils count (rs = 0.225; p = 0.001) in all samples. Upregulation of HMGB1 could be a significant marker typically in eosinophilic CRSwNP and it may also contribute to the pathogenesis of CRSwNP along with IL-5, IL-8, and TNF-α.

Systemic lupus erythematosus 2014.

Systemic lupus erythematosus 2014.

Expression of CD31/PECAM-1 (Platelet Endothelial Cell Adhesion Molecule 1) by Blastic Plasmacytoid Dendritic Cell Neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant neoplasm with cutaneous manifestations and a rapidly progressive clinical course. The diagnosis relies on characteristic clinicopathologic and immunopathologic features. However, the overlap of immunophenotypic features with other cancers, as well as newly discovered interpersonal and intrapersonal phenotypic variations, renders the identification of BPDCN challenging. A greater understanding of the proteins expressed by BPDCN might facilitate its recognition and provide insights into its clinical behavior. In 7 of 9 patients at 4 tertiary care institutions, immunohistochemical analysis demonstrated strong CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) expression by neoplastic cells. Combined with similar findings observed in 1 former patient, 8 of 10 cases of BPDCN were CD31/PECAM-1 positive. Expression of CD31/PECAM-1 by BPDCN adds new information about the antigenic profile of this unusual neoplasm. CD31/PECAM-1 influences multiple cell functions including adhesion, apoptosis, coagulation, host response, and protein synthesis that might affect clinical features of BPDCN such as hemorrhage, aggressive tumor growth, and resistance to therapy. Therefore, the potential role of this molecule in the tumor formation and progression of BPDCN warrants additional exploration.

Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp's syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia.

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.

Molecular diagnosis in autoimmune skin blistering conditions.

Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring.

Investigation of tumour-Infiltrating T cells and RANK/RANKL signalling in breast cancer

Aims First, to investigate the prognostic significance of T cell subsets and RANK/RANKL signalling in the primary tumour of locally advanced breast cancer (LABC) and metastatic breast cancer patients. Second, to investigate the predictive significance of a relationship between clinical response to the anti-RANKL monoclonal antibody denosumab and immunopathological features of the tumour cells. Methods Multiplex immunohistochemistry (IHC; Biocare) is used to assess the marker pairs CD4/CD8, RANK/PR and RANKL/FOXP3 in 84 patients in full-face serial sections and 60 patients in tissue microarrays with LABC or metastatic breast cancer. Aperio ImageScope software and ImageJ digital cell-counting algorithms are used to quantify total marker-positive cells as a percentage of total cells. Results Statistical analysis of data collected so far shows an independent positive trend between the presence of FOXP+ T cells or CD4+ cells, but not CD8+ T cells, and shorter disease free survival (DFS) and overall survival (OS) ( p = 0.089). Discussion Previous research on T cell infiltration and breast cancer outcomes has produced conflicting data. Our data demonstrate evidence on a large, targeted cohort on the relevance of the presence of different T cell subsets and outcome. This may represent a novel diagnostic tool.

Immunobullous disorders: Clinical histopathological and immunofluorescence study of thirty-six cases

Background: Immunobullous disorders are characterized by antibody-mediated bullous lesions affecting the skin and mucosa. Accurate diagnosis of these disorders requires clinicopathological correlation along with immunofluorescence study. Aims and Objectives: To study the clinical, histopathological, and immunopathological features of immunobullous disorders and to analyse the utility of immunofluorescence in the diagnosis of these disorders. Materials and Methods: A total of 36 cases of immunobullous disorders observed over a span of 2 years in our institution were studied. Detailed clinical examination, histopathological examination and immunofluorescence study were done in all cases. Results: Out of 36 cases studied, 18 cases (50%) belonged to pemphigus group, 10 cases (27.78%) were bullous pemphigoid (BP), 5 cases (13.89%) were linear IgA disease (LAD), 2 cases (5.56%) were cicatricial pemphigoid (CP) and 1 case (2.77%) was lichen planus pemphigoides (LPP). Twenty-one patients (58.33%) were in the age group of 21-60 years, 9 patients (25%) were above 60 years and 6 patients (16.67%) were below 20 years. Histopathology of all cases of pemphigus vulgaris (PV) showed suprabasal bulla with acantholytic cells. Pemphigus foliaceus (PF) showed subcorneal bulla in all three cases. Immunofluorescence in all 15 cases of PV showed IgG deposition in intercellular substance (ICS) and C3 deposition in ICS in six cases. PF showed IgG deposition in ICS in all three cases. BP and CP showed deposition of IgG and C3 in a linear band at basement membrane zone (BMZ) in all cases. All cases of LAD showed linear IgA band at BMZ. Conclusion: In three cases (two cases of BP and 1 LAD), immunofluorescence was absolutely essential to come to a final diagnosis, while in two cases of CP immunofluorescence helped in confirming the clinical diagnosis as histopathological finding was nonspecific. In the remaining cases it helped in confirming the diagnosis suggested by clinical examination and light microscopy.

Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis.

Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14+CD16+HLA-DRhigh monocytes and CD56dim cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ + and CD8+ T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8+ T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.

Noninfectious Immune-Mediated Uveitis and Ocular Inflammation

Noninfectious uveitis encompasses a diverse group of ocular inflammatory disorders that share an underlying immune etiology and may be associated with systemic disease or confined primarily to the eye. Uveitis is commonly classified by anatomical location of inflammation into anterior, intermediate, posterior, and panuveitis. The treatment of noninfectious uveitis consists of corticosteroids, immunosuppressive agents, and surgically placed steroid implants. We review the epidemiology, immunopathology, and clinical features of several noninfectious immune-mediated uveitides, including HLA-B27 acute anterior uveitis, juvenile idiopathic arthritis, intermediate uveitis, sarcoidosis, Behcet's disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and white dot syndromes. We also discuss the stepwise approach to medical treatment of immune-mediated uveitis as well as the characteristics, safety, and efficacy of immunosuppressive agents used to treat ocular inflammatory disease.

Lúpus eritematoso sistêmico bolhoso em gestante: relato de caso*

Systemic lupus erythematosus (SLE) can cause numerous skin lesions. Despite being rare, lupus-specifi c bullous lesions demonstrate characteristic clinical and immunopathological features and require differential diagnosis among numerous bullous conditions that may overlap with SLE. The present study presents a case of bullous systemic lupus erythematosus (BSLE) in a pregnant woman.

Bullous systemic lupus erythematosus in a pregnant woman: a case report*

Systemic lupus erythematosus (SLE) can cause numerous skin lesions. Despite being rare, lupus-specific bullous lesions demonstrate characteristic clinical and immunopathological features and require differential diagnosis among numerous bullous conditions that may overlap with SLE. The present study presents a case of bullous systemic lupus erythematosus (BSLE) in a pregnant woman.

Dangerous Construction: Crystalline Silica and the Silicosis Threat

Silica is an essential component of rocks, soil, and sand, and it is the second most common mineral on earth. Epidemiological studies indicate that crystalline silica poses a health risk when inhaled. This is an important issue because exposure to crystalline silica is widespread among many occupations, such as mining and construction. Exposure to crystalline silica is a problem in both developed and developing nations. It is estimated that 3,200,000 and 1,700,000 workers are exposed annually in the European Union and United States, respectively. In Canada, almost 350,000 workers are exposed every year. This paper provides an encompassing detail of crystalline silica and its negative health effects. First, the chemical and immunopathological characteristics are introduced. Second, the characteristics of silica dust are explored in order to define its health hazard processes. Finally, this paper focuses on the construction industry and introduces ways to control and prevent crystalline silica exposure.

Transition phénotypique d’un pemphigus vulgaire en pemphigus superficiel

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the two main subtypes of auto-immune pemphigus, each having different clinical, histological and immunopathological features. We report the case of a patient initially with typical PV who relapsed within 2years, presenting clinically, histologically and immunologically typical PF. A 47-year old man presented in March 2008 with clinically, histologically and serologically typical PV and treated with systemic corticosteroids alone (prednisone: 1mg/kg per day) then combined with a cycle of rituximab, which resulted in complete remission. After discontinuation of therapy (duration: 26months), he relapsed 6 months later with PF presenting clinical, histological and serological characteristics typical of this condition. This is a rare case of complete transition from PV to PF in clinical, histological and serological terms, and the first case occurring after initial treatment with rituximab.

Lupus erythematosus/lichen planus overlap syndrome: successful treatment with acitretin

Lupus erythematosus/lichen planus overlap syndrome is a rare disorder combining the clinical, histological and immunopathological features of both lupus erythematosus (LE) and lichen planus (LP). Cutaneous lesions mostly affect the distal arms, legs, face and trunk. Palmoplantar involvement is felt to be characteristic of this condition. Plaques are often painful, centrally atrophic, bluish-red to hypopigmented in color, large, and scaly. On biopsy of clinically ambiguous lesions, histopathological features of one or both processes can be found, obscuring the diagnosis and complicating prognosis and treatment. Thus, direct immunofluorescence has become an essential tool in helping to diagnose this condition. In this report we describe the unique clinical and immunohistopathological manifestations of lupus erythematosus/lichen planus overlap syndrome along with a successful response to treatment with acitretin.

Étude de trois cas de lupus érythémateux bulleux

Bullous lupus is a subepidermal autoimmune bullous dermatosis, a rare entity that forms one of the cutaneous signs of systemic lupus erythematosus. We report on the clinical, immunopathological and progressive features of bullous lupus in three patients. Our patients consisted of two women and one man aged 34, 22 and 30 years respectively. A diagnosis of bullous lupus erythematosus was evoked by blisters or vesicular blisters and confirmed, in addition to criteria for the diagnosis of systemic lupus erythematosus, by the presence of subepidermal blistering with infiltrate containing neutrophils and eosinophils as revealed by histological analysis, and of deposits of IgG and IgM (two cases) or of IgA (one case) at the dermo-epidermal junction observed under direct immunofluorescence. Indirect immunofluorescence showed anti-collagen VII antibodies. Lupus nephritis was present in two cases. Our patients were treated with corticosteroids and immunosuppressants. Bullous lupus erythematosus may be the first sign of systemic lupus erythematosus with severe visceral involvement, especially renal involvement, suggesting that it may be a marker of activity and prognosis.

Epidermolysis bullosa acquisita and inflammatory bowel disease: a review of the literature

We present a review of all previously reported cases of epidermolysis bullosa acquisita (EBA) and inflammatory bowel disease (IBD). We found 42 cases of coincident EBA and IBD in the literature: 35 cases of Crohn disease (CD) and 7 of ulcerative colitis (UC). The clinical and immunopathological features of the cases are described and the demographics collected. In the majority of cases, the diagnosis of IBD predated the development of the skin condition. The association between EBA and IBD was more common for CD than for UC. We discuss the immunopathogenesis of IBD and EBA, and also the link between them, namely type VII collagen.

Immunopathological characteristics of patients with bullous pemphigoid and neurological disease

The relationship between bullous pemphigoid (BP) and neurological disease has been the subject of numerous recent studies and BP antigens and their isoforms have been identified in the central nervous system (CNS). Whilst epidemiological data support this association, little is known about the pathomechanism behind this link and the immunological characteristics of patients with BP and neurological disease, other than multiple sclerosis (MS), has not been studied. We aimed to compare the cutaneous immune response in BP patients with and without neurological disease, to investigate whether or not there is a distinctive immunopathological profile in patients with concomitant BP and neurological disease. Seventy-two patients with BP were included and divided into two groups; those with neurological disease (BP+N, n = 43) and those without (BP-N, n = 29). Patients in BP+N group had a confirmed neurological disease by a hospital physician, neurologist or psychiatrist with positive neurological imaging where appropriate, or a Karnofsky score of 50 or less due to mental impairment. All sera were analysed with indirect immunofluorescence (IIF) using serial dilutions up to 1:120000, immunoblotting (IB) and Enzyme-linked immunosorbent assay (ELISA) for BP180 and BP230. Median antibody titres by IIF were 1:1600 vs. 1:800 for BP-N and BP+N, respectively, although the difference did not reach statistic significance (P = 0.93, Mann-Whitney U-test). ELISA values for both BP180 and BP230 did not differ significantly between the two groups. Similarly, autoantibodies to specific antigens as identified by ELISA and IB were not related to the presence of neurological disease. The results of this study indicate that patients with BP and neurological disease exhibit an immune response to both BP180 and BP230, thus the link between the CNS and the skin is not dependent on a specific antigen, but possibly both antigens or their isoforms may be exposed following a neurological insult, and play a role in generation of an immune response.

Management of Women with Recurrent Pregnancy Losses and Antiphospholipid Antibody Syndrome

Antiphospholipid antibodies (aPL) have been associated with recurrent pregnancy losses (RPL) and other obstetrical complications. The diagnostic criteria for the classical antiphospholipid antibody syndrome (APS) have been utilized for the detection of obstetrical APS in women with RPL. However, laboratory findings and immunopathology of obstetrical APS are significantly different from those of classical APS. In addition, many women with RPL who have positive aPL do not have symptoms consistent with the current APS criteria. The induction of a proinflammatory immune response from trophoblasts and complement activation by aPL rather than thromboembolic changes has been reported as a major immunopathological feature of obstetrical APS. Heparin treatment has been reported to be effective in prevention of early pregnancy loss with APS but not for the late pregnancy loss or complications. The complex effects of heparin may explain the limited efficacy of heparin treatment in RPL. New diagnostic criteria for obstetrical APS are needed urgently, and new therapeutic approaches should be explored further.

Acquired cystic disease-associated renal cell carcinoma: further characterization of the morphologic and immunopathologic features

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a subtype of renal cell carcinoma (RCC) with unique morphologic features found exclusively in the background of end-stage renal disease. We analyzed the clinicopathologic features and immumoreactive profiles of 12 cases of ACD-RCC to further characterize this recently recognized entity. Review of histologic slides was performed in conjunction with immunohistochemical staining directed to the contemporary diagnostic antibodies and the putative target therapy-related markers. Histologically, the tumors showed characteristic inter-or intracellular microlumens and eosinophilic tumor cells. Intratumoral hemosiderin deposition and degenerating foamy tumor cells were consistent findings which were not previously described. Immunohistochemically, all the tumors were positive for alpha-methylacyl-CoA-racemase, CD10, pan-cytokeratin, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and c-met, while negative for carbonic anhydrase-9, CD57, CD68, c-kit, pax-2, platelet-derived growth factor receptor (PDGFR)-α or vascular endothelial growth factor receptor (VEGFR)-2. Heterogenous staining was found for CK7 and kidney-specific cadherin. Positive reaction to c-met suggests its utility as a plausible therapeutic target in ACD-RCC. Thus, we present the unique morphologic and immunopathologic features of ACD-RCC, which may be helpful in both diagnostic and therapeutic aspects.