Identification of Leptosphaeria maculans Pathogenicity Group 4 Causing Blackleg on Winter Canola in Oklahoma.

Winter canola (Brassica napus L.) is a relatively new crop to Oklahoma and other southern U.S. states where it is considered a desirable rotation crop with wheat. In 2009, approximately 15,000 ha of winter canola were harvested in Oklahoma (3); that area is expected to almost double in 2010. Blackleg, a potentially devastating canola disease, was detected in Oklahoma in 2009. Blackleg is caused by Leptosphaeria maculans (Desmaz.) Ces. & de Not (anamorph = Phoma lingam (Tode:Fr.) Desmaz.). In early 2010, leaf samples showing typical symptoms of blackleg were collected from four canola fields near the town of Enid in Garfield County, OK. Small portions of infected tissues were surface disinfested in an aqueous solution of NaOCl (0.5% a.i.) for 1 min, rinsed twice in sterile distilled water, and plated on V8 medium. Seven colonies were isolated and when grown in pure culture, all produced 2 × 4.5 µm guttulate, unicellular, hyaline spores in pycnidia that ranged from 200 to 480 µm in diameter. These morphological characteristics correspond with those of P. lingam (1). To verify the pathogenic nature of the isolates and establish the pathogenicity group (PG) to which they belong, a standard inoculation protocol was followed on a set of three differential cultivars, Quinta, Glacier, and Westar (2). Briefly, for each isolate, tiny puncture wounds were made with sterile needles on the cotyledons of six 10-day-old plants of each differential and a 10-µl aliquot of a pycnidiospore suspension (1 × 107 spores ml-1) was deposited on the wounds. Also, a set of differentials were inoculated with distilled water (mock inoculation). Inoculated plants were incubated overnight in a misting chamber at 21°C in the dark and returned the next day to the greenhouse. Disease severity was recorded 10 days after inoculation using a 0 to 9 scale in which 0 to 2 = resistant, 3 to 6 = intermediate, and 7 to 9 = susceptible. This process was repeated three times. Two of the seven isolates evaluated were highly virulent on all three differentials, an indication they belong to pathogenicity group 4 (2). The other five isolates produced small lesions on Westar (resistant reaction) but failed to develop symptoms on the other two differentials. This phenotypic reaction has been associated with strains of PG-1. Mock-inoculated plants did not develop lesions. To our knowledge, this is the first time blackleg isolates from Oklahoma have been identified to the PG level. While this information will assist breeders in the development of both spring and winter canola lines with resistance to blackleg, additional studies are necessary to determine the relative prevalence and diversity of the various PG in Oklahoma. References: (1) G. H. Boerema. Trans. Br. Mycol. Soc. 67:289, 1976. (2) A. Mengistu et al. Plant Dis. 75:1279, 1991. (3) USDA. National Agricultural Statistics Service. Retrieved from http://www.nass.usda.gov/Statistics_by_State/Ag_Overview/ AgOverview_OK.pdf , September 20, 2010.

Ice encapsulation protects rather than disturbs the freezing lichen.

Arctic and alpine terricolous lichens are adapted to harsh environments and are tolerant to extremely low temperatures when metabolically inactive. However, there are reports indicating that freezing can be lethal to metabolically active lichens. With a projected warmer and more unstable climate, winter precipitation at high latitudes will fall more frequently as rain, causing snowmelt and encapsulating terricolous lichens in ice or exposing them to large temperature fluctuations. Lichens are a major winter food source for reindeer in most parts of the circumpolar region. A laboratory experiment tested how three hydrated reindeer forage lichen species covered by snow, encapsulated in ice, or uncovered responded to storage at freezing temperatures and subsequent warming. Photosynthetic performance (maximal fluorescence of dark-adapted samples and net photosynthetic rates) was significantly lower in lichens not insulated by snow or ice, whereas there were few differences between the snow and ice treatments. It is suggested that snow and ice provide sufficiently moist environments to improve extracellular and reduce intracellular ice nucleation activity. Ice encapsulation, which is often lethal to vascular plants, did not have any negative effects on the studied lichens. The results indicate that complete snow and ice melt followed by refreezing can be detrimental to terricolous lichen ecosystems. Reduced lichen biomass will have a negative effect both on reindeer winter survival and the indigenous peoples who herd reindeer.

A crossover, add-on trial of talampanel in patients with refractory partial seizures.

The authors report a double-blind, placebo-controlled, crossover study of talampanel in 49 patients with refractory partial seizures. Three doses of talampanel were investigated based on differences in patients' concomitant antiepileptic drug usage. Talampanel showed efficacy in reducing seizure frequency (p = 0.001) with a median seizure reduction of 21%. Eighty percent of patients had fewer seizures on talampanel than on placebo. Dizziness (52%) and ataxia (26%) were the only significant adverse events.

Genotyping of cytochrome P450 2D6*3 and *4 mutations using conventional PCR.

Cytochrome P450 (CYP450) mixed-function mono-oxygenases, consisting of more than 30 enzymes, are responsible for the metabolism of a large number of drugs and metabolites. With the rapid advances in the human genome project, the role of genetic polymorphism in drug metabolism may become an important adjunct for rational drug therapy, and for the explanation of drug toxicity and interactions. This preliminary study modified a previously described procedure for genotyping CYP2D6*3 and *4. An additional step included uracil-DNA glycosylase for the prevention of "carry-over" contamination. DNA was extracted from peripheral blood using PureGene DNA Isolation kit. CYP2D6*3 and *4 sequences were amplified by PCR, followed by digestion with restriction endonuclease Msp1 and Mva1, respectively. Resulting fragments were analyzed by electrophoresis and visualized by ethidium bromide staining. Poor metabolizers of *3 mutation showed 168-, 82- and 20-bp bands, while those of *4 showed a single 355-bp band. Using these protocols, 22 individuals were genotyped, showing the following prevalence for *3 and *4: 0 and 3, respectively-comparable to those of the general population. This method provides a reliable means of genotyping CYP2D6*3 and *4.

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.

BACKGROUND: Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. OBJECTIVES: To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. METHODS: Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas. RESULTS: Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect. CONCLUSIONS: Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry.

Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.

Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase.

Treatment options for patients diagnosed with chronic myelogenous leukemia (CML) in chronic phase (CP) who lack a suitable related donor for marrow transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or transplantation from an unrelated donor (URD). Most studies support the view that treatment with IFN-alpha results in prolonged survival compared with hydroxyurea therapy. Some patients are offered URD transplantation as a second-line treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD transplantation is uncertain. To address this question, we evaluated the effect of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN-alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha therapy administered for > or = 6 months was associated with an increased risk of severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR], 3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1; 95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha therapy. Increased mortality occurred between 100 and 365 days after transplant (P = .005), was limited to patients with severe acute GVHD, and was due to chronic GVHD refractory to immunosuppressive therapy. Other variables associated with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors, age greater than 50 years, weight > or = 110% of ideal body weight, and the absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with IFN-alpha for less than 6 months before transplant, who were < or = 50 years of age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5 years. These data provide a rationale for immediate transplantation in preference to extended treatment with IFN-alpha when the patient is < or = 50 years of age and has an HLA-compatible unrelated volunteer donor.

Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial.

Once daily topical treatment of psoriasis with tacalcitol ointment (4 micrograms/g) was compared with twice daily treatment with calcipotriol ointment (50 micrograms/g) in a double-blind, randomized study over a treatment period of 8 weeks. The severity of pruritus, erythema, infiltration and scaling was scored on a scale from 0 to 4. These features were scored at the initiation of treatment, after 2, 4, 6 and 8 weeks of treatment, and at 4 weeks after discontinuation of treatment. The sum score was the total score for erythema, infiltration and scaling. Serum levels of calcium, phosphate, ionized calcium and intact parathyroid hormone were used as safety parameters. Two hundred and eighty-seven adults with stable plaque psoriasis participated and were treated at least once. Both tacalcitol and calcipotriol ointments effectively reduced the severity of psoriasis. The mean reduction in the sum score in the intention-to-treat population of 287 patients was 4.03 in the group treated with tacalcitol compared with 5.05 in the group treated with calcipotriol. The mean baseline sum scores were 7.64 and 7.15, respectively. The acceptability of both ointments was excellent, and none of the patients had adverse effects in terms of increased serum calcium or other alterations in calcium metabolism. Although less effective than calcipotriol ointment used twice daily, tacalcitol ointment is an effective and useful once daily treatment of chronic plaque psoriasis.

Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% +/- 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose.

Transplantation of hematopoietic stem cells from an HLA-compatible unrelated volunteer is an option for patients with acute leukemia lacking a family match. However, criteria for patient and donor selection and the most effective transplant procedures, including the number of hematopoietic cells, remain to be defined. We tested factors influencing outcome of 174 patients with primary acute leukemia receiving non-T-cell depleted marrow from unrelated donors. Median patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found that leukemia in remission at the time of transplantation was associated with improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5, confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral blood, as opposed to marrow involvement only or isolated extramedullary relapse, was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to 5.0). The use of donors with a limited HLA-mismatch was associated with decreased leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free survival compared with HLA-matched unrelated donors. Transplantation of a marrow cell dose above the median value of 3.65 x 10(8)/kg was associated with faster neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5) engraftment, and decreased incidence of severe acute graft-versus-host disease (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a marrow cell dose above the median translated into less nonleukemic death (RR: 0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure: 0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells was associated with the best outcome in both children and adults.

IgG-Fc receptors in stratum granulosum: an immunological defence in human skin?

Receptors for the Fc-part of IgG (Fc tau R) in stratum granulosum of normal human skin were examined using cryosections and indirect immunofluorescence staining with 1) soluble immune complexes and 2) monoclonal antibodies (MoAbs) against different types of Fc tau R, i.e. 32.2 (anti-Fc tau I-CD64), IV.3 (anti-Fc tau RII-CD32) and Leu 11b (anti-Fc tau RIII-CD16). The immune complexes gave staining corresponding to stratum granulosum in sections from all skin specimens. Inhibition experiments showed that pre-incubation of the sections with monomeric and heat-aggregated human IgG, periodic acid and formaldehyde inhibited the immune complex binding. F(ab')2 containing immune complexes did not bind to the skin sections. The MoAb 32.2 gave granular and Leu 11b linear staining corresponding to stratum granulosum. In addition, both IC, 32.2 and Leu 11b gave weaker staining of keratinocytes in other parts of the epidermis. IV.3 stained epidermal Langerhans' cells and were unreactive with other epidermal cells. Indirect immunofluorescence staining with MoAbs against IgG subclasses showed the presence of all IgG subclasses in stratum granulosum. The results show that granulosum cells express both high- and low-affinity IgG receptors and in vivo bound IgG. The data point to a role for stratum granulosum in cutaneous immunity.

Hepatosplenic candidiasis--a contraindication to marrow transplantation?

To determine whether a prior history of hepatosplenic candidiasis resulted in increased Candida-associated morbidity and mortality after marrow transplant, 15 consecutive patients with biopsy-proven hepatosplenic candidiasis were observed prospectively. All patients received amphotericin B before transplant. Amphotericin B was continued at a dose of 0.5 mg/kg/day from conditioning through marrow engraftment, at which time it was discontinued if computerized tomography (CT) evidence of disease was stable or improved. Patients were observed for progression of candidiasis for the first 100 days after transplant. The amount and duration of antifungal therapy received before transplant varied widely. The majority of patients (73%) had persistently abnormal CT scans before transplant. After transplant, 3 of 15 died (20%) with evidence of fungal disease, although fungal species differed from those diagnosed pretransplant, compared with a historical mortality rate of 90% in posttransplant patients with documented hepatosplenic candida. Comparison CT scans obtained before and after transplant showed improvement in 9 of 15 (60%), complete resolution in 2 of 15 (13%), and none showed progression. We conclude that hepatosplenic candidiasis is not an absolute contraindication to marrow transplant when patients receive amphotericin B therapy before transplant and continue therapy until engraftment is established.

[Immunopathogenesis of atopic eczema]. / Immunpatogenese ved atopisk eksem.

The role of elevated serum IgE in patients with atopic eczema has been unclear. It has recently been shown that antigens from house dust mites may penetrate the skin, bind to IgE on Langerhans' cells, which in turn mediate the activation of antigen-specific TH2 cells that are the predominant T cells found in early atopic skin lesions. TH2 cells produce IL-4, which stimulates the IgE production by B lymphocytes, and are chemotactic for eosinophilic granulocytes. The discovery of microbial superantigens that activate T cells more easily and less specifically than the traditional antigens do, helps us to understand how local microbial agents can provoke the outburst of new atopic skin lesions.

Fc gamma-receptors in skin and serum from patients with psoriasis, before and after therapy.

IgG-Fc receptors (FcR) are present on most immune competent cells. We have examined FcR in skin lesions from 8 patients with stationary plaque psoriasis and 12 patients with highly active psoriasis using MoAbs against FcR and binding of soluble immune complexes. FcR in serum were measured in ELISA. The patients were treated with cyclosporin (n = 5), acitretin (n = 7) and Goeckerman regimen (n = 8). As controls served 8 skin biopsies and 22 sera from healthy individuals. Highly active psoriatic lesions showed strongest activity for FcRI, II and III and immune complex binding. The FcR+ mononuclear cells were located perivascularly and along the dermo-epidermal junction. The FcR activity decreased in correlation to the improvement following therapy. Epidermal Langerhans cells (LC) were positive for FcRII and immune complex binding. FcR activity on LC decreased during therapy. Keratinocytes expressed FcRI and III, irrespective of disease activity and therapy. FcR levels were lower in sera from psoriatics than in controls, median 0.15 vs. 0.27 (p < 0.01), and not correlated to disease activity. In 4 patients the FcR levels increased during therapy. The reduced levels of FcR in psoriatic sera might be due to consumption in the skin or anti-FcR autoantibodies.

Serum levels of interferons and TNF-alpha are not correlated to psoriasis activity and therapy.

Sera from 52 patients with psoriasis and 106 controls were tested for IFN-tau, IFN-alpha 2 and TNF-alpha in ELISA and for total IFN activity using an infectivity inhibition micromethod. Psoriasis patients had lower serum levels of IFN-tau than had the controls: median 0.10 ng/ml vs. 0.16 ng/ml (p = 0.01). The highest median serum IFN-tau levels were in patients with peripherally spreading psoriasis, 0.10 ng/ml, and acute guttate psoriasis, 0.09 ng/ml. Patients with stable plaque psoriasis had lower serum IFN-tau levels (median 0.0) than those with other forms of psoriasis, or blood donors. The serum levels of IFN-alpha 2, total IFN activity and TNF-alpha did not differ between the psoriasis and control group. Treatment with cyclosporin, acitretin and the Goeckerman regimen increased the total IFN activity, but did not affect the levels of IFNs nor TNF-alpha.

[Cyclosporine in the treatment of psoriasis]. / Cyklosporin i behandlingen av psoriasis.

Psoriasis is a chronic inflammatory skin disease of unknown etiology. An immune-reaction mediated by T lymphocytes is important in the pathogenesis. Cyclosporin is a selective immuno-suppressant that inhibits helper T lymphocytes. Several controlled clinical studies have shown that cyclosporin is highly effective in controlling severe psoriasis. The main side effects are hypertension, nephrotoxicity and increased risk of developing malignancies, particularly after long-term treatment. Side effects during short-term therapy appear to be reversible. Some questions connected to the long-term use and safety of cyclosporin are still unsolved.

Fc gamma-receptors on Langerhans' cells and keratinocytes in suspension from normal skin characterized using soluble immune complexes and monoclonal antibodies.

Fc-receptors for IgG (FcR) on epidermal cells in suspension were studied using soluble immune complexes and monoclonal antibodies (MoAbs) against FcR I, FcR II and FcR III using an indirect immunofluorescence technique. The binding of immune complexes demonstrated that most Langerhans' cells (greater than 95%) and a proportion of keratinocytes (25 +/- 6%) expressed functional FcR activity. The reactivity with MoAbs showed that epidermal cells possess different types of FcR. Langerhans' cells reacted only with IV.3 (anti-FcR II/-CDw32). A varying percentage of keratinocytes reacted with 32.2 (anti-FcR I/-CD64) (18 +/- 10%), Leu 11b (anti-FcR III/-CD16) (19 +/- 6%) and B1D6 (against a placental FcR) (35 +/- 8%). Both with immune complexes and MoAbs the staining was strongest along the cell surface, but cytoplasmic staining was also regularly present. The data add further support to the contention that keratinocytes have an immune function. FcR on epidermal cells may play an immunoregulatory role interacting with isotypes and cytokines in the skin. Keratinocyte-produced soluble FcR could also be an immunological mediator.