Hypersensitivity pneumonitis: a comprehensive review

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a complex pulmonary syndrome mediated by the immune system and caused by inhalation of a wide variety of antigens to which the individual has been previously sensitized. The pathobiology of the disease is not fully understood, but in addition to the triggers that initiate the disease, host/genetic factors are likely to be important, as only a minority of exposed individuals develop HP. Due to the lack of a diagnostic gold standard, the diagnosis of HP is not straightforward and relies on the integration of a number of factors, including history of exposure, precipitating antibodies to the offending antigen, clinical features, bronchoalveolar lavage, and radiological and pathologic features. However, in the appropriate setting, a high index of suspicion is critically important and may obviate the need for more invasive tests. Clinical presentation and natural history vary widely. Acute forms generally resolve without sequelae, while chronic forms, which are caused by persistent low-grade exposures, are associated with poor prognosis. Corticosteroids may be useful in acute episodes for symptomatic relief or in chronic and progressive disease, but their long-term efficacy has never been validated in prospective clinical trials. Ideally, patients with HP should be referred to centers with expertise, as the overlap with other forms of interstitial lung disease may be substantial. Making the correct diagnosis has critical therapeutic and prognostic implications (AU)

La neumonitis por hipersensibilidad (NH), también conocida como alveolitis alérgica extrínseca, es un síndrome pulmonar complejo mediado por el sistema inmune y provocado por la inhalación de una amplia variedad de alérgenos frente a los cuales el paciente está previamente sensibilizado. La patogénesis de la enfermedad se conoce parcialmente; sin embargo, además de los activadores iniciales que dan lugar al desarrollo de la enfermedad hay factores genéticos que tienen importancia también, de tal forma que solo una minoría de los individuos expuestos desarrollan la enfermedad. Debido a la falta de un 'gold estándar' para el diagnóstico de NH, se hace necesaria la integración de un número de factores, entre los que se encuentran la historia de exposición al alérgeno, la presencia de anticuerpos precipitantes frente al Ag ofensor, datos clínicos y datos patológicos en el lavado broncoalveolar, y radiológicos. En cualquier caso un alto índice de sospecha clínica es crítica y puede obviar la necesidad de otros test más invasivos. La presentación clínica y la historia natural de la enfermedad puede variar ampliamente desde las formas agudas que generalmente se resuelven sin secuelas a las formas crónicas fibróticas que son provocadas por la exposición de grado bajo mantenida y que se asocian con un peor pronóstico. Los corticosteroides pueden ser útiles en el tratamiento sintomático de los episodios agudos o en la enfermedad crónica progresiva, pero su eficacia a largo plazo nunca ha sido validada en ensayos clínicos diseñados para ese fin. La dinámica adecuada debe dirigir a los pacientes con MH a centros especializados expertos, dado que puede haber otras formas solapadas de enfermedad pulmonar y el diagnóstico correcto es crítico para la aplicación de un correcto tratamiento y un mejor pronóstico (AU)

[Aspergillus prostatitis and prolonged corticotherapy. Apropos of a case report]. / Prostatite aspergillaire et corticothérapie prolongée. A propos d'une observation.

Aspergillosis prostatitis is rare but more frequent to immunodeficiency people. We report a case of aspergillosis prostatitis associated with pulmonary tuberculosis, after a corticosteroid treatment for retroperitoneal fibrosis to Methysergide.

Immunological neutralization of cobrotoxin by its homologous precipitin and non-precipitin antibodies.

Anti-cobrotoxin antibodies can be separated into precipitin and non-precipitin antibodies. The precipitin antibody possesses the same binding affinity to cobrotoxin as non-precipitin antibody, but the neutralizing capability of the latter is superior to that of the former in blocking cobrotoxin binding to nicotinic acetylcholine receptor (nAChR). After preincubation with antibodies, cobrotoxin completely lost its binding activity to nAChR. The dissociation of cobrotoxin-nAChR complex by the antibodies was low, and 60% of the complex formation appeared to be irreversible. These results indicate that the neutralization of cobrotoxin by the antibody may predominantly involve unbound, receptor-free cobrotoxin. The relationships of neutralization capacity and binding affinity as well as bond strength between cobrotoxin and its antibodies are incongruous. Different local conformational changes of a unique Trp in cobrotoxin on binding with the precipitin and non-precipitin antibodies seem to lead to different accessibility for fluorescence quenchers. Characterization of the binding domains by immunoprecipitation with the antibodies correlated with the quenching results. Thus, the binding topography of cobrotoxin may play an important role over the binding affinity and bond strength in neutralization by cobrotoxin antibody.

Purification and amino-terminal sequence analysis of the complement-fixing and precipitin antigens from Coccidioides immitis.

Two proteins (21 and 48 kilodaltons) purified from endospore-spherule culture filtrates of Coccidioides immitis are identified as precipitin and complement-fixing antigens, respectively. To allow specific structural comparison to antigens identified by other investigators and as a first step to eventual serodiagnostic antigen production by recombinant DNA technology, amino-terminal amino acid sequences were determined for these antigens.

[Physico-chemical and immunochemical characteristics of oncoprecipitins of crustacin and cyprein specifically reacting with carcinoembryonic antigen]. / Fiziko-khimicheskaia i immunokhimicheskaia kharakteristika onkopretsipitinov krustatsina i tsipreina, spetsificheski reagiruiushchikh s rakovoémbrional'nym antigenom.

Crustacin from Pagurus prideauxii and cyprein from Cyprea caputserpentis have been shown to be glycoproteins with molecular masses 36 +/- 1 and 44 +/- 1.4 kDa, containing 3 and 18% of carbohydrates, respectively. Their amino acid and monosaccharide composition have been determined. Crustacin or cyprein interact with CEA more specifically than carbohydrate-containing polymers with lectins. Carbohydrates unspecifically inhibit this interaction at rather high concentrations. Association constants of CEA-crustacin and CEA-cyprein complexes are 0.6.10(8) M-1, respectively. Besides, ELISA showed that antibodies against CEA bind antibodies to crustacin and cyprein.

Serological and clinical investigation of humidifier fever.

A group of nineteen normally healthy subjects in a microprocessor factory reported various degrees of work-related respiratory and systemic symptoms that in some were suggestive of humidifier fever (HF). They all had normal serology against a variety of infectious agents, but serum-precipitating antibody against antigens in the factory humidifier water was present in twelve subjects, primarily those with symptoms most in keeping with HF. There was extensive serological identity between the antigens from this and other confirmed sources of HF. The antibody-positive subjects were all non-smokers and had significantly raised serum IgG. Nine months later, following modification of the humidifier system, the symptoms had resolved in fourteen of the nineteen subjects, the precipitins were reduced in seven but persisted in five subjects, and the total IgG levels were significantly reduced in all subjects. The measurement of total, as well as specific, IgG may be of value in assessing this disease.

Detection of protein variation in human serum by externally released precipitins from the blue crab, Callinectes sapidus.

1. A number of invertebrate species releases precipitins into the environment. This process is apparently part of an externally directed immunologic system. 2. A saline solution of precipitins released from the blue crab, Callinectes sapidus, provided a reagent that produced two different precipitation reactions with proteins from the sera of human individuals. 3. One of the reaction variants was also detected with mammalian antiserum, the other was not. The former variant was associated with a medical condition: hypergammaglobulinemia. 4. Saline reagents from different invertebrate species may prove useful in clinical diagnosis and for revealing new human protein polymorphisms.

Further studies on the alpha-precipitins of the Atlantic salmon (Salmo salar).

The alpha-precipitins of the Atlantic salmon have been isolated by a combination of chromatography and gel filtration. A monospecific antiserum has been raised and this has been used to measure the concentration of the antigen in 925 fish sera by CELISA. The results were analysed for the effects of sex and disease state of the animal, time of year and year of collection, and the part of the UK from which they were collected. Significant differences were found in all cases. The components of alpha-precipitin were investigated by the isoelectric focusing of pure alpha-precipitin, whole serum and serum heated for 18 h at 95 degrees C. Multiple banding occurred in the acid region of the gels; the number, relative strength and position of the bands depended upon the animal from which the serum was isolated.

Detection by ELISA of antibodies to small RNA protein particles in systemic lupus erythematosus patients whose sera lack precipitins.

Three hundred five consecutive patients with systemic lupus erythematosus (SLE) have been evaluated for antibodies to the RNA protein particles, Sm, nRNP, Ro/SSA, and La/SSB. Precipitating antibodies were found in 224 (73.1%). With the use of ELISA methodology with affinity-purified antigens, 76 sera from precipitin-negative patients were assayed and 35 had elevated levels of one or more of the autoantibodies. Of these, 27 (36%) had elevated anti-nRNP and 17 (22%) had elevated anti-Ro/SSA. Six of the seven patients with anti-La/SSB (18%) also had anti-Ro/SSA paralleling the close association of these two antibodies noted by precipitin analysis in which 38 of 39 patients with anti-La/SSB precipitins also have anti-Ro/SSA precipitins. Thus, 258 of the 305 SLE sera (84.6%) have elevated anti-RNA protein levels. This represents a minimum estimate of the frequency of these antibodies since longitudinal study of individual patients shows that anti-RNA protein levels may vary from normal to 1000 times over background at different times. Quantitative studies over time in two patients with both anti-Sm and anti-nRNP show that anti-nRNP increased 10- to 100-fold while anti-Sm changed little. These quantitative changes may relate to clinical phenomena.

Urodele egg jelly and fertilization.

Fertilization of urodele amphibians is physiologically polyspermic. These amphibians lack sperm entry blocking mechanisms at the egg surface, such as a cortical reaction or a membrane depolarization. Although, egg jelly is necessary for sperm capacitation, a late block to sperm entry does occur about 30 min after fertilization at a precise interface between jelly layers. The jelly is secreted by oviductal cells. In order to investigate its role in fertilization, we studied some biochemical properties of the oviductal secretions of eight species. In double diffusion experiments on agarose plates, some components secreted by the anterior and the middle parts of the oviduct interacted together and formed precipitin lines. This reaction might be responsible for the formation of the dense zone that delimits the capsular chamber. A hemagglutinating activity was found in the anterior or in the posterior part of the oviduct depending on the species. A 18K or 26K lectin was purified respectively from the oviduct of Ambystoma mexicanum and Pleurodeles waltl. In both species, the site where the late block to sperm entry is operative was spatially related to the location of the lectin in the jelly. However, sperm in contact with the purified lectins did not undergo any visible morphological change.

Relationships between antinuclear and anti-Ro/SS-A antibodies in subacute cutaneous lupus erythematosus.

A certain degree of confusion has arisen regarding the relationship between patients having subacute cutaneous lupus erythematosus (SCLE) and those with "antinuclear antibody-negative" systemic lupus erythematosus (ANA-negative SLE). One of the confusing issues relates to published differences in the autoimmune serologic findings of these two patient groups. In order to clarify this issue, we have screened the sera from thirty-seven patients with SCLE for the presence of fluorescent antinuclear antibodies (FANA) on two different substrates--human Hep-2 tissue culture cells and mouse kidney sections. In addition, these same sera were assayed for anti-Ro/SS-A precipitin antibodies. Seventy-eight percent of the sera were FANA-positive at a titer of 1:10 or greater when tested on human Hep-2 cells, whereas 76% were positive at a titer of 1:80 or greater. Fifty-one percent were positive on mouse kidney sections at a titer of 1:10 or greater, whereas 46% were positive at a titer of 1:20 or greater. Twenty-two percent of these sera were completely FANA-negative on both human and mouse substrates. None of these sera that were negative on both substrates contained anti-Ro/SS-A antibodies. However, 69% of the sera that were FANA-positive on both human and mouse substrates were found to have detectable anti-Ro/SS-A antibodies. Ninety percent of the SCLE sera that were FANA-positive on human Hep-2 cells, but negative on mouse kidney sections, contained anti-Ro/SS-A antibodies. These sera gave a speckle-like, or particulate, nuclear immunofluorescence staining pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

A precipitin for human serum proteins as released under stress by a marine invertebrate, the marsh snail, Littorina irrorata.

A substance released into the environment by stressed marsh snails, Littorina irrorata, precipitates with the beta globulin and albumin fractions of human serum proteins. Other diverse invertebrate species may produce a similar substance. Invertebrate precipitins have not been widely reported, and none like the one described. Some physicochemical and adaptive characteristics of the snail precipitin are presented. This precipitin can be produced in large quantities and has potential application as a diagnostic reagent.

Precipitins to an aflatoxin-producing strain of Aspergillus flavus in patients with malignancy.

Serum samples from 121 patients in whom malignant disease had been diagnosed, were assayed for precipitins to fungal isolates from leukemia-associated environments. Control sera were from age-, sex-, and race-matched patients with no history of malignant disease. Sera from 36 (30%) malignancy patients and seven (6%) controls yielded a precipitin band to an aflatoxin-producing Aspergillus flavus isolate from a leukemia-associated house (x2 = 222, p less than 0.05%). No significant numbers of precipitins were obtained to either of the other fungal isolates from that and another such house. Although A. fumigatus has frequently been incriminated as a source of infection in patients with malignancy, only 9% of malignancy patients had a precipitin response to it, as did 1.6% of controls. Also, the presence of the precipitins to A. flavus was not connected with past radiation or immunosuppressive therapy. However, among patients with precipitins to A. fumigatus there was a higher death rate in the year following the study. Precipitins to A. flavus may be related to heavy environmental exposure possibly leading to aflatoxin exposure which may contribute to development of malignancy though immunosuppressive effects.

Detection of IgG candida antibodies by solid-phase radioimmunoassay and comparison with agar-gel diffusion.

Comparison of solid-phase radioimmunoassay (S-PRIA) and agar-gel diffusion for detecting antibodies to candida organisms was undertaken in patients with systemic candidiasis, candida colonization, noncandida febrile illnesses, and in healthy controls. Radioimmunoassay results were highly reproducible when the same sera were tested on three different days. Sera from all three groups of patients had higher counts per minute (CPM) by S-PRIA then sera from control subjects. Although positive precipitins and high CPM occurred frequently in patients with systemic candidiasis, both precipitins and high CPM were detected in some sera from patients with colonization without system disease.

[Production of rabbit precipitating antisera to subclasses of human IgG]. / Poluchenie krolich'ikh pretsipitiruiushchikh antisyvorotok k subklassam IgG cheloveka.

Precipitating antisera to human subclasses IgG were obtained by immunization of rabbits by whole molecules IgG2, IgG3, IgG4 and gamma 1-chains derived from IgG1H (Pr). Analysis of the antisera obtained demonstrated that rabbits produced specific antibodies to the antigenic subclass determinants IgG3 well, to IgG2, IgG4--much worse, and failed to produce specific antibodies to subclass IgG1 (in immunization with whole molecules of this protein). Antisera contained antibodies to the antigenic determinants common of IgG, and antibodies to light chains which were removed by immunosorption, for which purpose a sorbent on the basis of BrCN sepharose conjugated with IgG of the three other subclasses and Fab-fragment was used.