Podocarpus gracilior and Callitris verrucosa--newly identified allergens that crossreact with Cupressus sempervirens.

Thirty-six symptomatic patients, with positive skin reactions to Cupressus sempervirens pollen extract were skin-tested with pollen extracts of Podocarpus gracilior and Callitris verrucosa, of these 17 (47%) had positive responses to P. gracilior, nine (25%) to C. verrucosa, and six (17%) to both. None of the non-atopic healthy controls had positive reactions to either of the extracts. Radioallergosorbent test (RAST)-inhibition studies were performed with pooled sera from three patients. Fifty per cent inhibition was obtained with 11 micrograms protein of C. sempervirens, 54 micrograms of P. gracilior, and 71 micrograms of C. verrucosa; however, when pollen extract of Olea europaea, an unrelated allergen, was tested, 265 micrograms protein were needed to obtain 50% inhibition. One-dimension sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of pollen extracts from the three species revealed that they had several very similar protein bands. Using Western blot analysis, several closely related IgE binding proteins were identified in the three species. It was concluded that the pollen grains of P. gracilior and of C. verrucosa are potentially allergenic. The presence of common allergenic proteins indicate partial crossreactivity with C. sempervirens.

Relationship between immunoglobulin levels and extremes of solar activity.

The possible relationship between epidemics and extremes of solar activity has been discussed previously. The purpose of the present study was to verify whether differences in the levels of immunoglobulins (IgA, IgG, IgM) could be noted at the highest (July 1989) and lowest (September 1986) points of the last (21st) and present (22nd) 11-year solar cycle. The work was divided into a 1-month study (covering the month of minimal or maximal solar activity), a 3-month study (1 month before and after the month of minimal or maximal solar activity) and a 5-month study (2 months before and after the month of minimal or maximal solar activity). A trend of a drop-off for all three immunoglobulins was seen on the far side of the maximal point of the solar cycle. Statistical significance was achieved in the 5-month study for IgM (P = 0.04), and a strong trend was shown for IgG (P = 0.07). Differences between the sexes were also noted.

Serum IgE concentrations, disease activity, and atopic disorders in systemic lupus erythematosus.

We investigated the relationship between disease activity and total IgE concentration in the sera of patients with active systemic lupus erythematosus (SLE). In addition, the prevalence of personal and family history of allergic rhinitis and asthma were examined with a questionnaire and immediate skin tests for common inhalant allergens in 24 patients in remission. In the 20 patients with active disease, we found that IgE concentration was significantly higher during the periods of active disease than the periods of remission. This elevation was not associated with an elevation in total serum IgG concentrations. The increase in IgE concentration during disease activity in patients with active nephritis was significantly higher than in patients without nephritis. Of the 24 patients in remission, only one reported allergic rhinitis, and two had positive skin tests for inhalant allergens. We concluded that, although patients with SLE do not have an increased rate of atopic disorders, serum IgE rises during disease activity and is associated with active nephritis. This phenomenon suggests that IgE may be involved in the pathogenesis of SLE, particularly in patients with nephritis.

Is granulocyte-macrophage colony-stimulating factor (GM-CSF) safe in myelodysplastic syndromes?

The complication of secondary myelodysplastic syndrome (sMDS) during the course of multiple myeloma (MM) has been recognized for more than a decade. sMDS occurs years after MM diagnosis, and typically, at sMDS presentation the MM is stable or inactive. We report a 56-year-old patient, who developed sMDS 15 years following the diagnosis of IgG-lambda MM, which had been completely stable for 13 years. However, very soon after sMDS was diagnosed, the MM relapsed and required combination chemotherapy. The first cycle of vincristine, adriamycin and dexamethasone (VAD) resulted in severe neutropenia and sepsis, which was treated with antibiotics and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Two weeks after GM-CSF administration a transformation to acute myeloblastic leukemia was observed. The relation between GM-CSF and the leukemic transformation is discussed and the possible contribution of the cytokine to the stimulation of this complication is emphasized.

Secondary myelodysplastic syndrome in multiple myeloma--a study of nine patients with an attempt to detect myeloma patients at risk.

Over a follow-up period of ten years, nine of our 100 patients with multiple myeloma (MM), developed myelodysplastic syndrome (MDS, preleukaemia). MDS occurred 19-156 (median 35) months from the diagnosis of MM. Six patients presented with pancytopenia and no patients had active MM at the time of MDS diagnosis. Three patients were defined as having refractory anaemia (RA) and six as refractory anaemia with excess blasts (RAEB) or RAEB in transformation (RAEBT), according to the FAB classification. The clinical course is characterized by increasing red blood cell and platelet transfusion requirements, recurrent infections and bleeding episodes. All patients, except for one, died within 3 to 8 (median 5) months from MDS diagnosis. The causes of death were sepsis or bleeding; three patients underwent leukaemic transformation. Thus, the clinical course of this small group of myeloma patients who developed secondary MDS (sMDS), was similar to other series of patients with sMDS. Serial bone marrow examinations suggest an initial hypercellular phase, followed by a rapidly evolving preterminal hypocellular marrow. In an attempt to detect MM patients at risk of developing sMDS, the epidemiological (including ethnic), clinical and laboratory data of the 9 MDS patients at the time of the MM presentation were reviewed and compared to the other MM patients. No significant differences were observed between the two groups in most parameters, except for two. All MDS patients were Ashkenazi Jews and no patients of Sepharadic origin developed MDS. Also, no IgA-myeloma patient developed MDS. If these findings are confirmed in a larger series, it may point to subgroups at risk which may require a different approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of disulfide bonds in an amyloidogenic Bence Jones protein leads to formation of "amyloid-like" fibrils in vitro.

Motivated by the finding that the amino acid sequence of the Bence Jones protein BJP-DIA was identical to that of the main protein component of the amyloid fibrils obtained from the same patient with AL-amyloidosis, (Klafki, H.-W., Kratzin, H.-D., Pick, A.-I., Eckart, K., Karas, M. & Hilschmann, N. (1992) Biochemistry 31, 3265-3272.), we attempted to create "amyloid-like" fibrils from the Bence Jones protein in vitro, without addition of proteolytic enzymes. Reduction of BJP-DIA, solubilized in PBS, pH 7.4, overnight at 37 degrees C resulted in the formation of a precipitate which had affinity for the dye Congo red. Electron microscopy of negatively stained samples of the reduced protein revealed aggregates of linear unbranched fibrils. SDS-polyacrylamide gel electrophoresis demonstrated that the precipitate consisted almost exclusively of intact light chain molecules. This result makes it possible to deduce a molecular model of these amyloid fibrils generated in vitro.

IgE response in multiple myeloma.

IgE levels in sera of patients with multiple myeloma (MM) were found to be similar to those of patients with monoclonal gammopathy of unknown significance (MGUS) and to normal controls. This is in contrast to the significant depression in the level of the other polyclonal isotypes in patients with MM. Immediate skin test response to common environmental allergens was also preserved in patients with MM as compared with normal nonatopic controls. One-year treatment of MM patients with alkylating agents caused a significant decrease in the monoclonal immunoglobulin level and induced a tendency toward decreasing IgE level but had no effect on the polyclonal immunoglobulin concentrations. These findings suggest that IgE production and immediate skin test response is not impaired by the pathologic process in MM patients, in contrast to the production of other polyclonal immunoglobulins. This demonstrates the dissociation between the response of the IgE antibody and the other isotypes.

Immediate adverse reactions to immunotherapy in allergy.

We report our experience of adverse reactions to immunotherapy (IT) in patients with insect venom allergy and inhalant respiratory allergy. Adverse reactions included large local reactions, generalized cutaneous reactions or systemic reactions. Among 87 patients treated for venom allergy, 43% had adverse reactions during the course of IT, averaging 2.5 reactions per patient and per course of IT. Nine had systemic reactions, of which 7 required adrenaline administration. Among 52 patients treated with inhalant allergen extracts, 40% had adverse reactions averaging 3 reactions per patient per course of treatment. Ten patients had systemic reactions but only 2 required adrenaline administration. There was no difference between the rate of adverse reactions in the venom and the inhalant treatment groups. IT has an inherent risk which has to be weighed against its benefits.

Complete amino acid sequence determinations demonstrate identity of the urinary Bence Jones protein (BJP-DIA) and the amyloid fibril protein (AL-DIA) in a case of AL-amyloidosis.

The complete primary structures of both the main amyloid fibril protein component (AL-DIA) and the soluble Bence Jones protein (BJP-DIA) obtained from the same patient with AL-amyloidosis are reported for the first time. The amino acid sequences were determined by automated Edman degradation following proteolytic digestion of the isolated proteins and HPLC separation of the resulting fragments and by amino-terminal sequencing after treatment with pyroglutamate aminopeptidase. Sequencing data were confirmed by amino acid analysis and plasma desorption mass spectrometry (PDMS). Molecular weights of the complete proteins were determined by laser desorption mass spectrometry. The amyloid fibril preparation contained a complete monoclonal lambda immunoglobulin light chain (subgroup 1.2) as well as different-sized fragments thereof which were identified by immunoblotting and amino-terminal sequencing following immobilization of electrophoretically-separated proteins on poly(vinylidene difluoride) (PVDF) membranes. The soluble urinary Bence Jones protein (BJP-DIA) was a dimer of monoclonal L-chains with a primary structure identical to that of the amyloid L-chain (AL-DIA) and thus represented the amyloid precursor protein.

Olive pollen induces asthmatic response.

We provide evidence that olive pollen extract can induce asthmatic response. The pattern of airway response to olive pollen is investigated. Nineteen patients with seasonal allergic rhinitis and asthma, suspected to be due to olive pollen, all of whom had positive skin-prick test, were investigated. Bronchial challenge with olive pollen extract were performed and the peak flow rate was followed for 20 hr. Eight patients developed dual asthmatic response (DAR), six patients developed early asthmatic response (EAR) and five patients had no asthmatic response. The early maximal fall in FEV1 and the PD15 were not different between the group with DAR and the group with EAR only. We conclude that olive pollen can induce dual asthmatic response.

1,25-Dihydroxyvitamin D3 potentiates the decreased response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine monophosphate.

The inhibitory effect of prostaglandin E2, histamine, isobutylmethylxanthine, and 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) on the mitogenic stimulation of peripheral blood lymphocytes from normal and atopic subjects was studied. We found that lymphocytes from atopic patients were less susceptible to inhibition by the three agents that elevate intracellular cyclic adenosine monophosphate (cAMP) concentrations and by the active metabolite of vitamin D (inhibition of 27%, 14%, 12%, and 36% for the atopic patients as compared with 40%, 20%, 22%, and 46% for the normal donors, by the four agents, respectively; p less than 0.02). The inhibitory effect of the cAMP-elevating agents was potentiated by the addition of 1,25-(OH)2D3 to the lymphocyte cultures. The potentiation was more pronounced on lymphocytes from the atopic donors, increasing their responsiveness to levels comparable to levels of lymphocytes from normal donors. The synthetic corticosteroid, dexamethasone, had a similar potentiating effect on the inhibitory action of prostaglandin E2. In view of the beneficial action of beta-agonists, phosphodiesterase inhibitors, and corticosteroids in the treatment of allergy, the potentiating effect of 1,25-(OH)2D3 on the action of cAMP-elevating agents may be of therapeutic interest.

[Prognostic factors in multiple myeloma].

There have been major advances in the treatment of multiple myeloma in the past 20 years, but for the individual patient the prognosis still remains uncertain. As the length of survival varies from several months to over 10 years, definition of prognostic parameters at the time of diagnosis, and early detection of disease activity are most important. In our study, median survival was 42 months with very good quality of life. Factors not helpful in prognosis were sex, WBC and platelet counts, BUN, serum M protein type, extent of osteolytic lesions, percentage of plasma cells in bone marrow and plasma cell asynchrony. However, age, hemoglobin, calcium, uric acid, Bence-Jones proteinuria and polyclonal Ig concentrations had a certain degree of prognostic importance. Due to more sensitive and more specific laboratory methods, peripheral blood findings are lately gaining in importance. With new "salvage" protocols, the detection of additional prognostic parameters and sensitive indicators of disease activity may be most important for further improvement in the survival of patients with multiple myeloma.

Corneal subepithelial monoclonal kappa IgG deposits in essential cryoglobulinaemia.

A 60-year-old man suffering from photophobia and visual disturbances was found to have bilateral superficial corneal grey-white gelatinous deposits. An abnormal cold-precipitable serum component was found and characterised as homogeneous IgG-kappa immunoglobulin. Corneal immunohistochemical examination revealed subepithelial IgG-kappa deposits, focally replacing Bowman's layer. The patient underwent superficial keratectomy in both eyes with satisfactory visual results.

Immunologic studies in Darier's disease.

Humoral and cellular immunity were evaluated in 10 patients with Darier's disease. The mean levels of serum immunoglobulins, serum complement, peripheral macrophages, and peripheral B and T lymphocytes were within normal limits. Secretory IgA was present in all patients studied. Skin tests for delayed hypersensitivity revealed complete anergy in one of the eight patients tested. Lymphocyte transformation tests revealed statistically significant enhanced responsiveness to both PHA and ConA mitogens in several concentrations studied. These findings may suggest either the existence of alterations in immunoregulation of lymphocyte subpopulations in Darier's disease or may be limited to alterations in membrane functions of certain lymphocyte subpopulations which can be detected only in vitro. The role that such immunologic aberrations may play in the pathogenesis of Darier's disease is still obscure.

Immunological response to immunotherapy for immediate hypersensitivity: clinical relevance.

Immunotherapy, also called desensitization, is effective in treating allergic rhinitis, insect sting venom hypersensitivity and probably allergic asthma. Administration of gradually increasing doses of the sensitizing antigen induces several immunological changes. The humoral responses include an increase in specific IgG titer, a decrease in specific IgE titer with blunting of its seasonal rise, and an increase in the specific anti-idiotype antibody titer. Cellular changes include diminished responsiveness of the patient's lymphocytes to stimulation by allergen as measured by thymidine incorporation. This is accounted for by the generation of suppressor cells specific for the allergen. These suppressor cells also induce suppression of IgE production by mononuclear cells. An additional effect that is attributed to IT is a decrease in basophil sensitivity to the allergen as measured by histamine release. The clinical correlates of these changes are not clear. Currently, none of the responses can be used as a tool for assessing the response in the treated individual patient. Although the increase in specific IgG was shown to correlate with the clinical response in patient groups, it is not applicable to the individual patient. Currently the best parameter for assessing clinical response is probably the increase in the ratio between the specific IgG and the specific IgE. However further studies are warranted to evaluate the significance of the change in anti-idiotype antibodies, basophil histamine release and perhaps immunological changes yet to be discovered.