Laryngeal graft after total laryngectomy in humans: A SWiM analysis.

Evaluation of the results of laryngeal transplantation (LT) in humans. Analysis of 3 bibliographic databases with the keywords "larynx, transplantation, autograft". In total, 626 abstracts were read and 25 articles selected. The main objective was to analyze the characteristics of laryngeal transplant patients. The accessory objectives comprised analysis of operative technique, immunosuppressive treatment and results. Four articles were selected for analysis. Two patients were transplanted after total laryngectomy for laryngeal carcinoma and 2 after laryngeal trauma. Three of the 4 patients had true transplantation with arterial, venous and neural microanastomosis. Two patients were decannulated and the tracheostomy tube was maintained in the other 2. Three of the 4 patients had good-quality phonation and could feed without a gastric tube. One patient died of carcinoma progression and 1 patient had to be explanted 14 years after transplantation. The number of LTs reported is too small for scientific determination of the place of this intervention in laryngology. The published results could, at first sight, suggest that the future of LT is uncertain. However, several elements, also suggest that otolaryngologists should continue to take an interest in this technique.

Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy.

Chronic vascular rejection characterized by the myointimal proliferation of smooth muscle cells that progressively obstruct the arterial graft lumen may become the main cause of long-term graft loss in vascularized composite allotransplantation (VCA), as observed in solid organ transplantation. As such, new diagnostic tools are required. The objective of this study was to evaluate the usefulness of flow magnetic resonance imaging (MRI) in the qualitative and quantitative monitoring of VCA in three patients transplanted between 2005 and 2012. Seven flow MRI acquisitions were performed concurrently with standardized clinical and histological monitoring between 2015 and 2017. A progressive reduction in the average flow rate and intraluminal diameter of the arterial pedicle of the grafts was demonstrated. During follow-up, two patients developed chronic vascular rejection requiring partial resection of the graft. For these patients, flow MRI acquisitions were characterized by a significant reduction in vascular signal, with a reduction in intravascular flow prior to anatomical injury. The results of this study confirm the feasibility of reproducible, non-invasive, and non-operator-dependent morphometric and haemodynamic radiological analysis, providing clinicians with new information on the vascular status of VCA over time and offering the prospect of an imaging technique specific to vascular outflow.

Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d'endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie - dialyse - transplantation (SFNDT).

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Face Transplantation: Partial Graft Loss of the First Case 10 Years Later.

Ten years after the first face transplantation, we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first posttransplantation year, at 90 months posttransplantation the patient developed de novo class II donor-specific antibodies, without clinical signs of AR. Some months later, she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis. Microscopic examination showed intimal thickening, thrombosis of the pedicle vessel, and C4d deposits on the endothelium of some dermal vessels of the facial graft. Flow magnetic resonance imaging of the facial graft showed a decrease of the distal right facial artery flow. Three steroid pulses of 500 mg each, followed by intravenous immunoglobulins (2 g/kg), five sessions of plasmapheresis, and three cycles of bortezomib 1.3 mg/m2 , were administered. Despite rescue therapy with eculizumab, necrosis of the lips and the perioral area occurred, which led to surgical removal of the lower lip, labial commissures, and part of the right cheek in May 2015. In January 2016, the patient underwent conventional facial reconstruction because during the retransplantation evaluation a small-cell lung carcinoma was discovered, causing the patient's death in April 2016.

Nocardiosis in transplant recipients.

Nocardiosis is a rare opportunistic infection caused by Nocardia spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. Despite recent progress regarding Nocardia identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of Nocardia. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.

Epstein-Barr virus-associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

Comparison of C4d detection on erythrocytes and PTC-C4d to histological signs of antibody-mediated rejection in kidney transplantation.

C4d on erythrocytes (EC4d), C4d peritubular capillary deposition (PTC-C4d) staining and histology were compared in a cross-sectional cohort of 146 renal allograft biopsies (132 patients). EC4d levels paralleled PTC-C4d staining, but were more predictive of peritubular capillaritis (PTC). Donor-specific antibodies (DSA), PTC-C4d, EC4d and PTC were analyzed in an independent longitudinal follow-up cohort (96 biopsies, 76 patients). Seventy-six samples were PTC and EC4d concordant, 11 positive and 65 negative, 7 PTC-EC4d+ and 13 PTC+EC4d-. EC4d levels were related to DSA occurrence. With ABMR defined by PTC and DSA, all apparently discordant patients, EC4d negative, were correctly reassigned comparing EC4d level curves with rejection kinetics, with positive EC4d samples predating biopsy or late biopsies compared with ABMR flare-ups. All EC4d-positive patients without PTC or DSA had permanent high EC4d levels unrelated to rejection. EC4d was more abundant in PTC-positive (mean = 108.5%± 3.4; n = 50) than PTC-negative samples (mean = 88.1%± 1.3; n= 96; p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of PTC-C4d and EC4d for PTC were, respectively, 75%, 79%; 64%, 76% (p < 0.05); 28%, 46% (p < 0.05) and 93%, 94%. Values were similar for DSA. A noninvasive blood test, EC4d, and particularly longitudinally monitoring EC4d levels, may increase surrogate ABMR testing options.

Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review.

Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.

Specificity of histological markers of long-term CNI nephrotoxicity in kidney-transplant recipients under low-dose cyclosporine therapy.

The specificity of chronic histological lesions induced by calcineurin inhibitors (CNI) is often questioned, but few studies have directly compared long-term lesions in renal-transplant patients who received this treatment and those who did not. We therefore conducted a retrospective study of 141 kidney-transplant recipients treated with (n = 48) or without (n = 93) cyclosporine (CsA) to compare the histological lesions observed at 3-month, 24-month and 10-year protocol biopsies. All of the chronic elementary lesions (glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, fibrointimal thickening) progressed in frequency and severity in both groups, although significantly more in the CsA group. Ten-year biopsy results showed that 92% of patients in the CsA-treated group and 65% in the control group had arteriolar hyalinosis lesions. When we focused on muscular arteriolar hyaline deposits more specific to CsA arteriolopathy, we observed these lesions in 68% of CsA patients and 28% of patients who had never received CsA. CsA was not the sole factor involved in the development of arteriolar hyalinosis and was independently associated with an increased risk of graft loss. In summary, we observed that histological lesions commonly attributed to CsA nephrotoxicity were not sufficiently specific to definitively diagnose CNI nephrotoxicity.

Advanced glycation end products assessed by skin autofluorescence in type 1 diabetics are associated with nephropathy, but not retinopathy.

AIMS: Advanced glycation end products (AGEs) are thought to play a central role in the pathogenesis of diabetes complications. For this reason, a non-invasive tool using skin autofluorescence (AF) quantification that correlates with levels of tissue AGEs has been developed. The present study aimed to assess whether or not skin AF is associated with microvascular complications in patients with type 1 diabetes (T1D). METHODS: All consecutive patients with T1D (n=133) had three AF measures taken on the forearm, using illumination with a fluorescent tube, all on the same day after breakfast or lunch. Potential associations between skin AF levels and microvascular complications, age, diabetes duration and health status were then assessed using a multivariate linear-regression model. RESULTS: On age-adjusted analyses, diabetes duration, retinopathy, nephropathy and neuropathy were significantly associated with skin AF levels (all P<0.001). AF levels increased significantly with severity in both retinopathy and nephropathy (P<0.001). After adjusting for age, diabetes duration, HbA(1c), smoking, retinopathy, nephropathy and neuropathy, the association of AF levels remained significant with nephropathy and neuropathy, but not with retinopathy and diabetes duration. CONCLUSION: This study suggests an independent association between skin AF levels and diabetic nephropathy and neuropathy, but not retinopathy, in T1D patients. Prospective studies are needed to confirm the ability of skin AF levels to predict microangiopathy.

Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells.

OBJECTIVES: The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses. METHODS: We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX). RESULTS: Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it. CONCLUSION: MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.

[Hand allografts: experience from Lyon team]. / Allogreffe de mains: expérience lyonnaise.

Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level of amputation was at the wrist or at the mid-forearm. Delay since hand loss ranged from 2.5 to 9 years. The surgical protocol was elaborated and planned case by case. All recipients received the same immunosuppressive treatment. Episodes of acute rejection were observed in the first 3 months after transplantation, which were easily managed after a few days increasing oral prednisone doses and applying topical immunosuppressants. Currently the patients receive the doses of immunosuppressants comparable to those in kidney-grafted patients. We have not registered any severe complication of immunosuppressive treatment up till now (7 years follow-up for the earliest graft). We performed analytical and functional clinical, as well as questionnaire evaluation of patients. The first case (unilateral graft) resulted in graft failure at 2 years due to non-compliance of the patient. The three bilateral graftees demonstrate a favorable evolution despite some immunological (hyperglycemia, serum sickness) and surgical (thrombosis, osteomyelitis, skin loss) complications, which could be managed. The middle and long-term follow-up evaluation revealed good to excellent sensorimotor recovery of 4 hands in both male recipients (4 and 7 years) with satisfactory social adaptation, higher or equal to those expected after post-traumatic replantations at the equivalent level and higher to those obtained with currently available myoelectric prosthesis. The last patient, a young female who has been grafted in February 2007, receives ongoing reeducation course and shows normal progress of functional restoration of both hands. The encouraging results of this clinical experimentation make us currently consider hand allografting as reasonable and useful both for the patients and for evolution of research in composite tissues allotransplantation (CTA). Further long-term careful research and worldwide monitoring of all patients with hand allografts is required to, on the one part, state on the authorization of this surgery, and, on the other part, to better elucidate the mechanisms of successful CTA.

Quantification of interstitial fibrosis by image analysis on routine renal biopsy 1 year after transplantation in patients managed by C2 monitoring of cyclosporine microemulsion.

BACKGROUND: Renal interstitial fibrosis (IF), the main histopathologic feature of chronic allograft nephropathy (CAN), may be an important surrogate endpoint for patient follow-up. IF is currently assessed by semiquantitative analysis, but automatic color image analysis may be a more reliable, reproducible method to evaluate IF. We performed a retrospective analysis to calculate IF on routine renal biopsies 1 year after transplantation. METHODS: Data were obtained from MO2ART, a prospective multicenter trial in which the cyclosporine microemulsion dose was adjusted based on C(2) levels. We included 26 patients in whom routine renal biopsy at 1 year was available from two centers. For each biopsy, a section was analyzed by a program of color segmentation image that automatically extracted green-colored areas characteristic of IF. Results were expressed as percent IF and grade namely grade I, <25%; grade II, 25% to 50%; and grade III, >50%. The results were compared according to clinical and biological data. RESULTS: The 26 patients had a mean IF score of 0.35 +/- 0.04. We observed 34.6% CAN grade I; 46.1%, grade II; and 19.2%, grade III. Serum creatinine at 3 years was greater in the higher grade of automated IF by repeated ANOVA. CONCLUSION: Automatic quantification of IF on routine biopsy at 1 year after transplantation was predictive of renal outcome. This technique may provide an interesting tool for the early diagnosis of CAN after renal transplantation.

High pretransplantation soluble CD30 levels: impact in renal transplantation.

In a retrospective study, the impact of the level of pretransplantation soluble CD30 molecule (sCD30) was evaluated on 3 year transplant survival, as well as the number and grade of acute rejection episodes among kidney recipients engrafted between 2000 and 2002. One hundred and ninety sera of 190 patients sampled on the cross-match day were tested for sCD30 concentrations using an enzyme-linked immunosorbent assay (ELISA) kit (Biotest). For the analysis, a sCD30 cutoff level of 100 U/mL was chosen: 87 (46%) recipients had a level >100, and 103 (54%) <100. All cases (5) of immunological graft loss showed a high sCD30 level. The rate of biopsy-proven acute rejection was 26% in the sCD30 >100 group versus 22% in the sCD30 <100 groups. Among the first graft population (n = 157), the rate was 27% for sCD30 >100 versus 20% for the lower level. The difference was more important for grade II acute rejection (Banff criteria): 6/87 (7%) showed high sCD30 versus 2/103 (2%) with sCD30 <100. This analysis became significant for anti-HLA immunization: 11 (13%) recipients developed anti-HLA class II antibodies in the first group (sCD30 >100) versus 1 (1%) in the second group (sCD30 <100; P < .01). A high pretransplantation sCD30 was not a significant risk factor for an acute rejection episode, but it seemed to be more predictive for antibody-mediated acute rejection and immunological graft loss. However, many recipients showed an increased pretransplantation concentration without any rejection episode or graft loss. Consequently, sCD30 pregraft measurements cannot be used as a predictor for acute kidney rejection among our transplant center, nor as an aid to adapt the immunosuppressive regimen.

["Facial graft": about the first facial allotransplantation of composite tissues]. / Greffe de visage: regards portés sur la première allotransplantation composite partielle de la face.

The first facial allograft was realised in Amiens 2005 November 27th. Breaking the technical limits of the so called possible and in appearance transgressing some cultural forbidden in organ transplantation, this resolutely innovative intervention open more than new perspective in the surgery of the reconstruction after disfigurement, but also a wide field of scientific investigations about dynamic and meaning of the facial function. Obviously, it also deals with numerous ethical and medical problems. The authors here shortly described the technical points of the surgery firstly done to restore oral function and facial expressively, the principles of the immunosuppressive treatment built to control any rejection time episode and the anatomical, neurological and functional results obtained after more than 18 months follow-up. Those perfectly demonstrate the perfect morphological, dynamic and cortical integration of the graft in the recomposed face. They also allow to confirm the legitimacy of the surgical indication and to oppose the factual objective arguments to the ethical reticences dealing with the facial and psychological identity of the receptor.

[Sirolimus-induced onychopathy in renal transplant recipients]. / Onychopathie associée au sirolimus chez les transplantés rénaux.

INTRODUCTION: A large number of drugs may be responsible for the development of nail changes. Sirolimus is an immunosuppressive drug recently developed in organ transplantation. Herein, we evaluate sirolimus-induced nail abnormalities in renal transplant recipients. PATIENTS AND METHODS: The nails of 80 consecutive renal transplant recipients receiving sirolimus have been evaluated in a systematic dermatological study in 2003. The patients were mainly men (60%) with a mean age of 48 years. The mean duration of the graft was 6 years and of sirolimus treatment 18 months. Mycophenolate mofetil and steroids were combined with sirolimus in 86% of patients. RESULTS: Fifty-seven patients (74%) complained for nail alterations. The most frequent anomalies (88%) were matrix alterations including slow growth, onychomalacia, onychorrexis, and leukonychia. Nail bed alterations (onycholysis), vascular phenomenon (erythema, splinter hemorrhages), and periungual anomalies (mainly pyogenic granulomas) were observed in 42, 42 and 19% of cases respectively. One observation of type 1 photo-onycholysis was described. DISCUSSION: This study reports a new drug-induced onychopathy. Responsibility of sirolimus is highly suggested. The main pathogenesis hypothesis to explain these nail alterations is inhibition of EGF (epidermal growth factor) pathway by sirolimus.

[EBV-associated cutaneous plasmocytoma in a renal transplant patient]. / Plasmocytome cutané EBV+ isolé chez une malade transplantée rénale: efficacité d'un traitement par rituximab.

INTRODUCTION: Postransplant lymphoproliferative disorders are well known complications of solid organ transplant, usually associated with Epstein-Barr virus (EBV). OBSERVATION: A 25 year old renal transplant patient presented with two subcutaneous nodules on the lower limb that appeared 3 years after a second renal transplantation. Biopsy of one nodule showed an EBV associated plasmocytoma located in the subcutaneous tissue. A complete systemic evaluation showed no evidence of extracutaneous involvement. The patient was treated with anti CD20 therapy (rituximab), and complete remission was achieved. DISCUSSION: Extranodular localisations of postransplant lymphoproliferative disorders are usually reported, but cutaneous localizations are rarely described. Histological presentation are various, but plasmocytoma-type is infrequent. Initial therapy of cutaneous EBV-associated postransplant lymphoproliferative disorders without extracutaneous involvement consists in reduction of the immunosuppression therapy and/or an antiviral treatment and prolonged surveillance. Treatment with monoclonal anti-CD20 antibodies (rituximab) is proposed.

Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.

BACKGROUND: Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. METHODS: Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis. RESULTS: Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months. CONCLUSIONS: Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.

The failure of Daudi cells to express the cellular prion protein is caused by a lack of glycosyl-phosphatidylinositol anchor formation.

The cellular prion protein (PrPc) is a glycosyl-phosphatidylinositol (GPI)-linked cell surface protein, which is expressed at high density on nervous tissues and at lower levels on most other solid-organ tissues. It is also expressed on peripheral blood mononuclear cells (PBMC) of all lineages. In lymphocytes, its level of expression is dependent upon the state of cell activation, and polyclonal anti-PrP antisera partially block lectin-induced T-cell activation, suggesting a functional role of the protein in this process. Using the monoclonal antibody (mAb) 3F4 we examined PrPc surface immunoreactivity on leukaemic cell lines of T- and B-cell origin, and unexpectedly observed a complete lack of PrPc cell-surface expression in Daudi cells, while all other cell lines displayed discernible reactivity. We demonstrated the intracellular presence of PrP-specific mRNA and PrP protein. The lack of surface PrPc is unrelated to the well-known defect of beta2-microglobulin (beta2m) expression in Daudi cells as other beta2m-deficient cells, such as the melanoma cell line F0-1 and spleen cells from beta2m gene-deleted mice, were not deficient in cell-surface PrPc. Daudi cells failed to bind antibodies directed against all GPI-linked cell surface proteins. In somatic hybridization experiments using murine spleen cells as partners, we observed de novo expression of human PrPc, CD55 and CD59, thus demonstrating in Daudi cells the availability of these gene products for GPI linkage and cell-surface expression.