Mixed Cellular Infiltrate Research Articles

Beta 2-integrins in different forms of urticaria.

As urticarial lesions involve tissue invasion by inflammatory cells, and as beta 2-integrins play a central part in adhesion of leucocytes to endothelia, allowing their migration into the tissues, we have explored the distribution and sequential expression of these molecules in tissue sections from different forms of urticaria. Prick test weals (of 10 min duration) to common inhalant allergens showed only a minor increase of CD18, whereas in a case of cold urticaria CD11b and CD18 molecules were increasingly upregulated within the first 30 min after elicitation of the lesions. Skin test sites in delayed pressure urticaria, and urticarial lesions (> 6 h duration) of acute and chronic recurrent urticaria also showed marked upregulation of CD11b and CD18, and to a lesser extent of CD11a, but this did not strongly correlate with the intensity of the mixed cellular infiltrate. Non-lesional skin showed expression of beta 2-integrins in chronic urticaria, delayed pressure urticaria, and less so in acute urticaria, suggesting generalized leucocyte activation. This analysis of integrins thus suggests an early and extensive involvement of these molecules in the pathological events associated with the evolution of urticarial lesions.

Recurrent pyogenic granuloma treated with topical imiquimod

To the Editor: A 56-year-old white male presented with a 4-month history of a “bleeding wart.” At presentation, the lesion was a 7-mm friable, red, vascular papule at the proximal portion of the left third digit (Fig 1). Histologic examination of an excisional biopsy demonstrated a sharply circumscribed, crusted papule with collarette of epithelium at each end. The dermis showed a lobular proliferation of small vascular spaces surrounded by fibrous tissue and mixed cellular infiltrate consistent with pyogenic granuloma.

A case of imported paracoccidioidomycosis: an awkward infection in the Netherlands

Paracoccidioidomycosis is an important endemic mycosis in South America. In Europe the disease is very rare and only found as infections in travelers to Latin America. We report here the first case encountered in the Netherlands for which the appropriate diagnosis was not attained for several months. A Dutch 60-year-old man presented with a painful ulceration in the buccal mandibular vestibular mucosa of three months duration. While his medical history was uneventful, he had worked, until 8 years prior to his presentation, as a carpenter for 25 years in the jungles of Peru and Ecuador. An aberrant chest radiograph, CT-scan of the lungs and increased erythrocyte sedimentation rate were suggestive of sarcoidosis or a bronchiolitis obliterans organizing pneumonia. There was no improvement in the patient's symptoms despite the use of budesonide and prednisone medication, as well as tuberculosis prophylaxis with isoniazide and rifampicin, and local use of miconazole. Quite to the contrary, as an irritated, irregular hyperemic mucosa and gingiva with ulceration were noticed during this period of time. These precipitated an incisional biopsy through which a mixed inflammatory cellular infiltrate and large yeast cells were found on histopathologic examination. Based on the patient's travel history and the multiple budding yeastlike cells revealed in the biopsy tissue, the diagnosis of paracoccidioidomycosis was finally made. This was supported by the isolation of Paracoccidioides brasiliensis in culture. Antimycotic oral therapy with itraconazole was started and continued for 15 months. At two and five year follow-ups, the patient was asymptomatic. In Europe, it may be expected that diseases that are endemic in other areas will be seen more frequently in countries where the diseases are not routinely encountered. It is most likely that the use of corticosteroid medication, with its inherent immunosuppressive effect, resulted in the reactivation of an infection acquired many years before in Latin America. The etiologic agent then disseminated from the initial focal point to cause the ensuing oral mucous membrane lesions. The importance of the patient's prolonged residence in Latin America was overlooked. The very long latency of endemic mycoses emphasizes the need for a meticulous history which should include not only recent trips, but also past residence in foreign countries.

Intrahepatic biliary epithelial cell damage and inflammation in portal tract in association with chronic colitis-harboring TCRα−/− mice

Intrahepatic bile ducts are the target for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The mechanisms of biliary epithelial cell damage in both diseases are not clearly understood. Ulcerative colitis (UC) is one of the known complications in PSC. In this study, we assessed the possible influence of apoptosis inhibitor expressed by macrophages (AIM) on intrahepatic bile ducts in the chronic colitis-harboring condition by generating T cell receptor alpha-deficient (TCRalpha(-/-))xAIM-deficient (AIM(-/-)) double-knockout mice. TCRalpha(-/-)xAIM(-/-) mice were generated by crossbreeding TCRalpha(-/-) mice with AIM(-/-) mice. At 24 weeks of age, mice were sacrificed to obtain liver tissues for pathological examinations, and blood was collected to study the serum levels of IgG, IgM and IgA. In female TCRalpha(-/-)xAIM(-/-) mouse livers, mixed cellular infiltration in the portal area and epithelial cell damage in bile ducts were observed, when compared with female TCRalpha(-/-)xAIM(+/-) and male TCRalpha(-/-)xAIM(-/-) mice. Inflammation in hepatic parenchyma was mild to none in all mice. In the female mouse group, the serum IgA level was relatively increased in TCRalpha(-/-)xAIM(-/-) mice compared to TCRalpha(-/-)xAIM(+/-) mice. The defect of AIM might be involved not only in colonic mucosal inflammation but also in portal inflammation, as well as in biliary epithelial cell damage in the livers of female TCRalpha(-/-)xAIM(-/-) mice.

Leukocytapheresis treatment for pyoderma gangrenosum

A 42-year-old man presented with painful erythema with pustules and multiple small ulcers on the shins. He had suffered from ulcerative colitis (UC) and received oral glucocorticosteroid and salicylazosulfapyridine therapies for 7 years. Biopsy of the lesion demonstrated mixed cellular infiltrates with dominant neutrophils. The patient was diagnosed with pyoderma gangrenosum (PG) and underwent leukocytapheresis (LCAP), an extracorporeal leucocyte removal therapy, once a week for 5 weeks without changing the doses of the oral medications. The skin lesions as well as clinical signs of UC rapidly improved after LCAP, and no recurrence was seen during a follow-up period. There were no major complications during LCAP. LCAP will provide an effective and safe tool for the treatment of PG.

ANTI-CD154 MAB TREATMENT BUT NOT RECIPIENT CD154 DEFICIENCY LEADS TO LONG-TERM SURVIVAL OF XENOGENEIC ISLET GRAFTS

O404 Aims: Rejection of islet xenografts is primarily mediated by a cellular immune response and can be modulated by costimulatory blockade. The aim of our study was to evaluate the role of CD40-CD40L pathway in the rejection process of concordant and discordant islet xenografts. Methods: Streptozotocin-induced diabetic C57BL/6, CD40- knockout (KO) or CD40L-KO mice were transplanted under the kidney capsule with either rat islets (300 islets) or human islets (1000 islets). For rat-to-mouse and human to-mouse combination, 4 experimental groups were performed (6 recipients per group): Group 1, islet transplantation (TX) in C57BL/6 mice without further therapy; Group 2, islet TX in C57BL/6 mice with anti-CD154 mAb (MR1) therapy (0.5mg i.p. on days 0, 2 and 4); Group 3, islet TX in CD40-knockout mice and Group 4, islet TX in CD40L-knockout mice. Islet function was measured by glycemia and histology was performed on regular intervals. Results: Short-term MR1 therapy significantly prolonged both concordant (median graft survival (MGS) >120 vs 17 days for controls, p < 0.001) and discordant xenograft survival (MGS >120 vs 11 days for controls, p < 0.005), compared to controls. In CD40-KO mice, concordant xenograft survival was shorter compared to control (MGS 9 versus 17 days, p = 0.5), but discordant xenograft survival was prolonged (MGS 27 versus 11 days, p = 0.06). In CD40L-KO, concordant xenograft survival (MGS 17 versus 17 days) and discordant xenograft survival (MGS 16 versus 11 days) was not significantly modified compared to controls. In Group 1, histology obtained at rejection showed dense graft infiltration by immune cells and IgG, IgM and C3 deposition. In Group 2, histology performed after 120 days showed a mixed cellular infiltrate around intact islets, without antibody or C3 deposition. In Groups 3 and 4, a moderate cellular infiltrate was observed at rejection, with no IgG, but moderate IgM and C3 deposition. Conclusions: Short-term anti-CD154 mAb therapy significantly prolonged rat-to-mouse and human-to-mouse xenograft survival compared to control groups. In CD40 KO and CD154 KO groups, survival of concordant or discordant islets was not prolonged significantly compared to control groups. Improved graft survival among the anti-CD154 mAb treated mice could potentially be explained by specific targeting of activated T cells with subsequent inactivation by anergy and/or elimination by apoptosis, complement- or cellular-mediated mechanisms. Rejection of xenografts in CD40 or CD154 KO animals is possible through the efficient activation of alternate pathways of costimulation.

18-FLUORO-DEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY MAY CONTRIBUTE TO THE DIAGNOSIS AND FOLLOW-UP OF MALAKOPLAKIA

Malakoplakia is a rare inflammatory disease involving most frequently the urinary tract. We present a case of bilateral renal malakoplakia, in which FDG-PET contributed to diagnosis. We made this diagnosis on the basis of clinical presentation, renal biopsy showing a mixed cellular infiltrate with granuloma formation and possible Michaelis-Gutmann bodies, resolution of the lesions after prolonged antibiotic therapy and evidence of leukocyte dysfunction. We briefly discuss the pathofysiology and therapy of this rare and difficult to prove disease and the role of FDG-PET in the diagnosis of inflammatory and infectious diseases.

Immunisation with vimentin causes rejection of syngeneic cardiac grafts

The role of non-HLA antibodies following solid organ transplantation is unclear. In patients, antibodies to the autoantigen vimentin are associated with transplant associated coronary artery disease after cardiac transplantation. However, whether these antibodies are directly damaging or a bystander effect is unknown. Here we have investigated survival of cardiac grafts in mice undergoing and an immune response to vimentin. C57BL/6 mice received two subcutaneous injections (7 days apart) of recombinant vimentin in Freunds incomplete adjuvant, controls received urea in saline. Two weeks after the first injection they received heterotopic heart transplants from syngeneic or allogeneic (129/sv) donors. Hearts were palpated every day to estimate graft survival and rejected hearts were subjected to histological and immunocytochemical analysis. Antibodies to vimentin were quantitated by ELISA. Immunised mice (n = 7) produced signficant IgG anti-vimentin titres at two weeks after immunisation (mean titre 516+/−365, compared to controls 5.75+/−6.3, p = 0.001). The survival of syngeneic hearts in saline/urea immunised mice was 100% at 32 days (n = 7) whereas the mean survival time of the syngeneic heart in vimentin immunised mice (n = 7) was 14.1+/−4.3 days (p = 0.0007). Histology of the mice’s own hearts demonstrated no effects of vimentin immunisation. The mean duration of allogeneic grafts in saline immunised and vimentin immunised mice was not different (at 7.4 and 7.0 days respectively). Histology of the rejected hearts showed myocyte necrosis, vascular thrombosis and a mixed cellular infiltrate. Immunocytochemistry showed no T cells in the syngeneic grafts. Immunoglobulin from vimentin immunised but not control mice bound to cultured C57BL/6 mouse endothelial cells treated with hydrogen peroxide (91.7% vs 22.8% ) but not to normal endothelial cells (3.5% vs 3.5%). In conclusion, the results suggest that the autoimmune response to vimentin is potentially damaging and that surgical manipulation maybe sufficient to sensitise the grafts to autoimmune damage.

Contribution of Flow Cytometry in the Diagnosis of Cutaneous Lymphoid Lesions

The histologic diagnosis of cutaneous lymphoid lesions remains one of the most challenging areas of dermatopathology and is augmented by incorporation of immunophenotypic and genotypic data. To improve the analysis of surface Ig light chain expression and to increase the yield of immunophenotypic data obtained from skin biopsies, we evaluated the utility of flow cytometry in cutaneous lymphoid infiltrates. Flow cytometric immunophenotypic analyses were performed on skin specimens of 19 patients as a part of diagnostic procedures. We found that skin biopsy specimens, including a routine punch biopsy, yield sufficient material for diagnostic flow cytometry. One reactive lymphoid hyperplasia showed polyclonal B cells and no aberrant T cell populations. Ig light chain restriction was detected by flow cytometry and contributed to the diagnosis in 88% (15 of 17) of cutaneous primary or secondary B cell lymphomas, compared to 37% (three of eight) by immunohistochemistry. Nearly one-third of these cases were histologically suspicious but difficult lesions due to processing artifact, mixed cellular infiltrate, or paucity of abnormal cells. Additional markers (3-23) were analyzed by flow cytometry on 15 specimens, and contributed to subclassification of the lymphomas. Our experience demonstrates that flow cytometry can be successfully applied to routine skin biopsies and contributes to the diagnosis and subclassification of cutaneous lymphoid lesions.

The molecular basis for the generation of Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is a lymphoid neoplasm with a low frequency of malignant tumor cells, known as Hodgkin and Reed-Sternberg (H-RS) cells, in a background of mixed cellular infiltrates. Despite extensive studies on H-RS cells, the molecular mechanisms of their growth and regulation have remained uncertain for a long period. Recently, constitutively activated nuclear factor-kappaB (NF-kappaB) was reported to be a unique and common characteristic of H-RS cells that prevents the cells from undergoing apoptosis. NF-kappaB triggers proliferation and provides a molecular basis for these cells' aberrant growth and cytokine gene expression. In HL pathogenesis associated with Epstein-Barr virus infection, the activation of NF-kappaB is induced by viral latent membrane protein 1 (LMP1). Coupled with recent insights into the molecular mechanisms of activation of NF-kappaB signaling in H-RS cells, this review discusses a linkage between LMP1 and HL via CD99, which has recently been reported to be down-regulated by LMP1 through the NF-kappaB signaling pathway. This down-regulation leads to the generation of cells with H-RS phenotypes related to the clinical and histologic characteristics of HL.

Preliminary findings in corneal allograft rejection in patients with keratoconus

Purpose Classically , corneal allograft rejection is thought to be a T H1-mediated phenomenon. However, T H2-mediated allograft rejection has been reported in other transplanted organ systems, including the heart and kidney. We previously reported a form of T H2-mediated corneal allograft rejection in a murine model with a T H2 immune bias. In this study we sought to determine if there was any evidence for this form of corneal allograft rejection in humans. Design Experimental study with an interventional case series. Methods The clinical records of all keratoconus patients undergoing penetrating keratoplasty at the University of Texas, Southwestern Medical Center from 1994 to 1999 were reviewed. Careful attention was paid to a clinical history of atopy. Atopic patients were selected, because these patients have been shown to have a “T H2 immune bias.” The corneal graft rejection rate in these patients and the number of repeat corneal transplants performed was determined. The experimental group consisted of patients with a clinical history of atopy and keratoconus who had at least one repeat penetrating keratoplasty for an immunologically rejected corneal transplant. Any patient with evidence of primary allograft failure was excluded from this study. Tissue specimens from these patients were embedded in paraffin, serially sectioned, stained with Giemsa stains, and examined histologically. The control group consisted of patients without a clinical history of allergy (and therefore no T H2 immune bias) who underwent corneal transplantation for Fuch corneal endothelial dystrophy, or aphakic/pseudophakic bullous keratopathy. Failed grafts from these control patients were also paraffin embedded, serially sectioned, stained, and examined histologically. The human experimental and control corneal specimens were compared with data obtained in a murine model of T H2-mediated corneal allograft rejection. Briefly, full-thickness penetrating C57BL/6ByJ corneal allografts were transplanted onto Balb/cByJ and Balb/c-IFN-γ tm1Ts (Balb/c-IFN-γ knockout) mice. Additionally, full-thickness Balb/cByJ corneal allografts were transplanted onto C57BL/6ByJ and C57BL/6ByJ-IFN-γ tm1Ts mice. Corneal allograft rejection rates and mean rejection times were calculated and compared between wild-type and interferon gamma (IFN-γ) knockout hosts. The rejected allografts were examined histologically by the same methods used in the human tissue. Results There were 84 penetrating keratoplasties performed from 1994 to 1999 for keratoconus. Seven of these 84 patients rejected their corneal grafts. Of the 7 patients who rejected their corneal allografts, 4 had repeat penetrating keratoplasty. Of these 4 repeat corneal allografts, 3 showed eosinophilia when compared with rejected grafts in control patients. Atopic keratoconus patients had a mixed inflammatory cellular infiltrate in the rejected corneal tissue specimen with a significantly greater density of eosinophils ( P = .001) compared with patients who did not have a pre-existing T H2 bias. The inflammatory infiltrate in these patients without a T H2 immune bias was mononuclear. In the murine model, corneal allograft rejection did occur in the absence of IFN-γ, a critical T H1 cytokine in both fully allogeneic donor–host combinations. Histologically, rejection in these (“T H2 mice”) was characterized by a predominant eosinophilic infiltrate in the rejected graft bed when compared with wild-type animals (“T H1 mice”) that had a predominately mononuclear infiltrate in the rejected corneal graft bed. Conclusion Preliminary findings show that corneal allograft rejection in patients with a pre-existing T H2 phenotype is similar to what is seen in the murine model of T H2-mediated corneal allograft rejection. Based on this small sample, it appears that eosinophils may play a role in corneal allograft rejection in this group of patients. However, further study is necessary to determine the importance of these cells in allograft rejection.

Relationship of jute dust to interstitial fibrosis in rat lung.

The relationship between jute dust and lung interstitial fibrosis was studied by instilling groups of rats, via trachea, with jute dust and comparing the results with those for positive (quartz) and negative (saline) controls. The rats were sacrificed at regular intervals and their lungs and hilar lymph nodes were analyzed for collagen content and morphologic changes. The earliest changes consisted of alveolar edema, increased numbers of intraalveolar macrophages, and marked thickening of the interalveolar septa, with mixed cellular infiltrates. Moderate thickening of the alveolar walls and the zones around the peribronchioles was seen in the test groups at 6 mo. After 12 mo, some fibrosis of the alveoli walls and peribronchiole zones occurred. Interstitial cellular nodules were observed occasionally, composed mainly of dust particles, fibroblasts, reticular fibers, and collagen fibers. The collagen content in the lungs of the jute dust groups was significantly higher than for the saline control group for all test periods. The authors conclude that jute dust may induce lung interstitial fibrosis.

A treatment for biliary hypoplasia: tube cholecystostomy and irrigation.

Biliary Hypoplasia (BH), characterised by a small ductal system and reduction in the number of interlobular bile ducts, has a bad prognosis. It has been claimed that other treatment methods apart from liver transplantation are not effective. Seven patients with BH underwent tube cholecystostomy, decompression and saline irrigation of the biliary tree via tube cholecystostomy. We present our treatment method, together with the early and late biochemical and histopathological results of these patients. The records of seven patients with BH were reviewed retrospectively. BH was proved by operative cholangiography. Irrigation was performed intermittently with warm saline to the biliary tract via tube cholecystostomy over two to three months. SGOT, SGPT, alkaline phosphatase (AP) and bilirubin levels were evaluated preoperatively and postoperatively. Histopathological findings were also evaluated. Median age at operation was 46 days (range 20 - 90 days). There were six males and one female. Five patients recovered completely. There was a statistical difference between preoperative and postoperative SGOT, SGPT, AP, and bilirubin levels of patients who recovered (p < 0.05). Similar to biliary atresia, many factors such as the patient's age, postoperative bilirubin level, histopathology of liver, treatment method, and cholangitis as a complication of the surgical procedure affect the prognosis of BH. Operation before the age of 70 days, normal bilirubin levels after operation, no cholangitis attack, intracellular and intracanalicular cholestasis, and mild mixed cellular infiltration are favourable factors. We believe that decompression and irrigation of the biliary tract is an effective treatment method for suitable cases of BH.

Experimental study on fibrogenic effect of fur dust on rat lung.

The fibrogenicity of fur dust was studied in rat lung tissues. Intratracheal instillation of fur dust, morphologic examination of lungs and analysis of collagen content were performed in Wistar rats. Morphologic examination revealed that the earliest changes consisted of alveolar edema, increased numbers of intraalveolar macrophages, and marked thickening of interalveolar septa with mixed cellular infiltrate. After sixth months, there was moderate thickening of the alveolar walls and the peribronchioli. After 12 months, interstitial positive fibrosis of the alveolar wall and the peribronchioli were weakly seen. In the carding dust group (silica content 17.6%), interstitial nodules were observed composed of fibroblasts, reticular fibers, and collagen fibers. Electron microscopic examination also showed that alveolar walls became thickened and collagen fiber bundles were seen around bronchioles and small vessels in the carding groups after 12 months. At all stages of analysis, the collagen content in lungs of the fur dust groups was significantly higher than that of the control group. Our study suggested that fur dust might induce weak interstitial fibrosis in the lung.

Immunopathogenesis of accelerated allograft rejection in sensitized recipients: humoral and nonhumoral mechanisms.

Accelerated rejection (AccR) in sensitized recipients (second-set rejection) is considered a classic humorally mediated form of allograft rejection, although additional effector mechanisms may be involved. We developed a model of AccR in which C57BL6 mice are sensitized by BALB/c skin grafts, followed 10 days later by transplantation of BALB/c hearts. We undertook analysis of various humoral and cellular components in this model using knockout or monoclonal antibody-treated allograft recipients. Sensitized mice rejected cardiac allografts in 34+/-7 hr. AccR was accompanied by endothelial deposition of immunoglobulins, complement, and fibrin, but also by dense expression of multiple chemokines and a mixed polymorphonuclear and mononuclear cellular infiltrate. Whereas neutrophil or complement depletion had no significant effect on the tempo of AccR, surprisingly B cell-deficient recipients still underwent AccR (41+/-7 hr) in conjunction with T cell and macrophage recruitment. In contrast, T cell-deficient (nude) mice maintained functioning cardiac allografts for >720 hr despite prior skin engraftment. AccR in sensitized experimental recipients involves multiple effector pathways. Although most previous studies have emphasized the key role of humoral pathways in mediating AccR, our data indicate that T cell-dependent mechanisms can also promote AccR, alone or in conjunction with humoral responses.

Autoradiographic quantification of 18F-FDG uptake in experimental soft-tissue abscesses in rats.

To use semiquantitative autoradiography to investigate fluorodeoxyglucose (FDG) uptake, distribution, and cellular localization in acute, early chronic, and late chronic soft-tissue infections. Unilateral calf-muscle abscesses were induced in 12 Sprague-Dawley rats by means of intramuscular inoculation of 0.1 mL of bacterial suspension (Staphylococcus aureus, 1.2 x 10(9) CFU/mL). Following injection of 130-180 MBq of fluorine 18 FDG, autoradiography of the abscess and contralateral muscle was performed (10-microm section thickness) on days 2, 5, and 9 after infection. Detailed spatial correlation of autoradiographs and histopathologic samples was performed by means of image fusion. Regions of interest were placed in the abscess wall, and measured gray values were converted to kilobecquerels per cubic centimeter according to kilobecquerels of injected activity per gram of body weight, which yielded standardized uptake values (SUVs). Acute abscess formation was characterized by central necrosis predominantly surrounded by neutrophils and a second necrotic tissue layer that bordered neutrophil infiltrates peripherally. Areas with increased FDG uptake corresponded to cellular inflammatory infiltrates, mainly granulocytes. The corresponding SUV was calculated to be 4.08 +/- 0.65 (mean +/- SD). Early chronic phase showed mixed cellular infiltrate of granulocytes and macrophages that surrounded central necrosis with interspersed fibroblasts and only residual muscle necrosis layer within the abscess wall. FDG uptake was located where granulocytes and macrophages were present, as in acute infection (SUV = 5.32 +/- 2.30). Late chronic infection was characterized by a prominent layer of macrophages around residual central necrosis and fibroblast-enriched granulation tissue delineating the infection from muscle tissue. FDG uptake clearly coincided with the macrophages, and no substantial increase of FDG uptake was detected within fibroblast-enriched granulation tissue. The SUV was calculated as 7.97 +/- 0.21. Results of Kruskal-Wallis ANOVA demonstrated that the change in SUV with time was statistically significant (chi(2) = 7.42, P <.05). The highest FDG uptake coincides with areas of inflammatory cell infiltrates, predominantly in neutrophils in the acute phase and in macrophages in the chronic phase of soft-tissue infection.

Eosinophilic angiocentric fibrosis of the sinonasal tract: Report on the clinicopathologic features of a case and review of the literature

Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory lesion of the sinonasal tract that occurs mainly in young to middle-aged female patients. Only two previous cases affecting male patients have been reported, and its etiopathogenesis remains unknown. The authors report on the third case of the entity in a male patient and review the 12 previously reported cases. A 52-year-old male patient was initially seen with a 15 years history of allergic rhinitis, progressive nasal obstruction, and left-sided hearing loss. All laboratory tests were unremarkable, except the nasal discharge eosinophil count that showed a conspicuous eosinophilia. The video-assisted-nasofibroscopic examination and CT scans disclosed a thickened deviated nasal septum with a subjacent infiltrative lesion. The histologic analysis of the nasal septum showed a variable mixed inflammatory cellular infiltration mainly composed of eosinophils, plasma cells, and histiocytes with a perivascular distribution; in other areas, an angiocentric fibrosing lesion with a peculiar perivascular onion-skin pattern was observed. The patient had a partial resection of the lesion with symptomatic control. The presence of rhinitis and nasal eosinophilia in our case associated with the clinical aspects of the previously reported cases further support an allergic cause for EAF.

Molecular biology of Hodgkin's lymphoma

Hodgkin's lymphoma (HL) is characterized by typical mononucleated Hodgkin and multinucleated Reed-Sternberg cells, which occur at low frequency in a mixed cellular infiltrate in the tumor tissue. Because of the rarity of these cells and their unusual immunophenotype, which is strikingly different from those of all normal hematopoietic cell types, the origin of these cells and their clonality have long been unclear. Single-cell studies of rearranged immunoglobulin genes showed that Hodgkin and Reed-Sternberg (HRS) cells represent clonal tumor-cell populations derived from germinal center B cells. In classical HL, the detection of obviously crippling immunoglobulin gene mutations in a fraction of the cases suggests that HRS cells may derive from germinal center B cells that have lost the capacity to be positively selected by antigen and that normally would have undergone apoptosis. In rare cases, HRS cells represent transformed T lymphocytes. The transforming events involved in malignant transformation of HRS cells are still largely unknown. Constitutive activation of the transcription factor NFkappaB, which can, for example, be induced through Epstein-Barr virus transformation of HRS cells or destructive somatic mutations of the inhibitor of NFkappaB, is likely to be a key event in HL pathogenesis. Significant progress has been made in our understanding of the cellular interactions in HL tissues, which are mainly mediated by a large variety of cytokines and chemokines.

Histopathology of chronic urticaria.

Urticaria of undetermined cause persisting longer than 6 wk is known as chronic idiopathic urticaria (CIU). The differential diagnosis of CIU is lengthy and a skin biopsy may be of value in making a more precise diagnosis. The histopathologic feature that differentiates chronic urticarial lesions from acute urticarial lesions is the presence of a mixed cellular perivascular infiltration, composed mostly of mononuclear cells, surrounding the dermal postcapillary venules. Mast cell numbers in CIU lesions may be increased compared to normal dermis. Various patterns of histopathologic findings have been described in CIU. An understanding of these patterns of infiltrating cells, mediators, cytokines, chemokines and adhesion molecules may provide insight into the mechanism of the cutaneous disease and provide valuable information that will help in the selection of a more effective therapeutic intervention.

Murine graft-versus-host disease induced using interferon-gamma-deficient grafts features antibodies to double-stranded DNA, T helper 2-type cytokines and hypereosinophilia.

Acute, lethal graft-versus-host disease (GvHD) develops in B6D2F1 hybrid recipients of wild-type, C57BL/6, parental strain grafts; however, when interferon-gamma (IFN-gamma) gene knockout (gko) donors are used, the disease is prolonged and associated with a higher level of engraftment, particularly of T cells. Lesions containing large, mixed cellular infiltrates develop in the skin, liver, pancreas, salivary gland, lung and kidney. In our current study, we wished to determine whether GvHD features a preponderance of T helper 2 (Th2) cytokines in the absence of donor-derived IFN-gamma, and whether autoantibody production, commonly associated with chronic GvHD, also occurs. Because mitogen responsiveness is consistently suppressed in mice with acute GvHD, we wished to measure this response in recipients of IFN-gamma gko grafts. Our findings indicate that spleen cells from the latter produce interleukin (IL)-4, IL-5 and IL-13 in culture, but respond poorly to concanavalin A (Con A) and lipopolysaccharide (LPS). Their sera contain anti-nuclear antibodies (ANA), some of which are specific for double-stranded (ds)DNA and are predominantly immunoglobulin (Ig)M and IgG1. We also noted the presence of numerous eosinophils in the infiltrates developing within the target organs. In some respects, this syndrome bears resemblance to both systemic lupus erythematosus (SLE) and chronic GvHD. However, histological evidence of glomerulonephritis is lacking and proteinuria fails to develop in recipients of IFN-gamma gko grafts, suggesting that IFN-gamma may be necessary for the development of lupus nephritis. On a broader scope, our findings underscore the importance of IFN-gamma in the pathogenetic mechanism of GvHD, and demonstrate that the absence of this cytokine promotes the development of chronic GvHD and autoimmunity.