[Some new immunological tests: Application for pathological field (author's transl)].
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A study of the possible interference of urinary proteins with all the commercial in vitro pregnancy products on the market in the United States today was carried out by our group. Six of these tests were of the tube type and seven were slide tests. Radioimmunoassays and receptor assays for beta human chorionic gonadotropin (beta-HCG) were not tested. The products examined showed interferences by urinary proteins presented at various levels. Interference by human serum albumin (HSA) (in five tube tests) occurred only at a physiologically improbable, high concentration of HSA (5 g/dL). However, in certain cases interferences by serum proteins (false positive type) occurred at concentrations lower than 0.06 g/dL which are physiologically probable. The four tests formulated to work with both serum and urine did not show any urinary protein interference with HCG measurements. There was no clear difference in urinary protein interferences between the tube and the slide tests; the tube tests were slightly more sensitive to the presence of HSA. Those tests employing latex beads, as opposed to erythrocytes, showed greater sensitivity to protein interferences.
The clinical value of the immunological tests performed routinely has been evaluated in 91 patients with various histological types of glomerulonephritis. An antigen possibly involved in the pathogeny of renal disease was found in 24% cases. However, in most instances no direct link between the presence of this given antigen and the disease could be observed. Therefore systematic investigations for antigens should be restricted to dosages of antistreptolysin and antinuclear antibodies and to determination of Hbs antigen. Immune complexes, which were observed in many cases, were of no discriminant value for the clinician. Dosages of the complement fractions and the determination of cryoglobulins can be helpful for diagnostic, follow-up and treatment. Our results justify a restricted selection of the routine immunological tests used in patients with glomerulonephritis. More specific investigations remain useful when they are clinically oriented.
The Food and Drug Administration (FDA) is classifying fecal calprotectin immunological test systems into class II (special controls). The special control that will apply to these devices is the guidance document entitled, "Class II Special Controls Guidance Document: Fecal Calprotectin Immunological Test Systems." The agency is classifying these devices into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of these devices. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document that will serve as the special control for these devices.
Our objective was to determine whether results from tests for maternal serum antinuclear antibodies, cytotoxic antibodies to paternal lymphocytes, parental histocompatibility types, and blocking factors for maternal-paternal mixed lymphocyte reactions were predictive of pregnancy outcome without immunologic treatment. Pregnancy outcome data from 95 women with a history of unexplained recurrent spontaneous abortions who underwent immunologic tests at Jefferson Medical College were evaluated with multiple logistic regression analyses. The number of prior spontaneous abortions, history of another relevant diagnosis, parental sharing of one histocompatibility antigen, and maternal age were related to the outcome of the next pregnancy in women given no immunologic treatment (p = 0.05). No significant correlation was found between results from the immunologic tests or other history characteristics evaluated and outcome of the next pregnancy. The immunologic tests evaluated were not clinically useful predictors of pregnancy outcome.
Of 11 immunological tests done on chronic fatigue syndrome patients and on fatigued controls, 3 tests (protein A binding, Raji cell, or C3 or C4 [deviant values in either complement component were counted as positive]) with deviant results discriminated best among the groups. Other tests, including immunoglobulin G subclasses, complement component CH50, interleukin-2, and anticardiolipin antibodies, did not discriminate well among the groups.
No correlation between the clinical course of trichinellosis and the level of positive titre in immunological tests and total activity of LDH was found. In severe courses of trichinellosis, however, the maxima of total LDH activity appeared earlier. In the described epidemics of trichinellosis the increase in iso-4 and iso-5 of LDH was followed by an increase in LDH activity in 50% of cases, but the maxima in both the biochemical tests appeared 1-6 weeks earlier than the maxima in the immunological tests. For this reason, the biochemical tests could be of diagnostic value in the first weeks of invasion.
For the evaluation of immunological tests during an epidemiological survey and of vaccination with the PI brucellin vaccine, in an occupationally exposed environment, a sample group of 354 subjects was studied. The vaccinal strategy was based on the outcome of a skin test for hypersensitivity: the PS brucellin test. In this framework, the serological status and evolution of individuals with positive or negative reactions to this test were analysed. Sera were studied using the buffered antigen test, indirect fluorescence immunoassay and Wright's agglutination test, as well as by PACIA and ELISA techniques with assay of IgG, IgA and IgM antibodies. The PS test, which was pivotal in this study, was compared with the lymphoblastic transformation test. One prominent aspect of this evaluation was the establishment of conventional prognostic indices for the PS and serology. The PS is definitely shown to be a convenient, reliable tool for screening. Although it does not generate sensitivity it may modify the serological status of both positive and negative individuals.
Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged "multiple chemical sensitivity" and/or "environmental illness." According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental "immunotoxins" is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many cases. Without consideration of these factors, a patient might be erroneously diagnosed as having some form of "immune dysregulation," "environmental immune dysfunction," or "immunotoxic" syndrome on the basis of only a single panel of cellular immunologic profiles or related immunologic tests illustrating slight deviations from the norm and in the absence of overt disease on physical examination. Consideration must also be given to an understanding of biologic variability and diurnal variations in lymphoid cell numbers in interpreting cellular immunologic profiles. For example, the necessity for age and sex-matched controls, test reproducibility, quantitative versus functional assays, and the significance of major versus minor deviations from the norm must be appreciated. In addition, many other conditions can effect immunologic tests, such as medications, psychologic factors, cigarette smoking, and the presence of concurrent disease, including minor viral infections. All of these variables should be appreciated in test interpretation. Certain clinical indications for analysis of cellular components of the immune system, using flow cytometry, have been provided as guidelines although they are by no means accepted by all groups due to their current incomplete evaluation by the clinical immunology community. These suggested indications are discussed. In this article, attempts are made to outline the various quantitative and functional tests used to assess the immune system, with emphasis on "biomarker" tests to detect possible immune system "damage." Dangers involved in attempting to make clinical evaluations based on results of isolated in vitro assessment of quantity or function of immune system cellular and humoral components without considering the results of a good medical history and physical examination, the many pitfalls involved in the tests, and the many confounding variables that affect the tests are emphasized, as well as the need for proper controls...
The outcome of immunologic tests of antibodies directed against hapten conjugates of organic acid anhydrides and human serum albumin (HSA) has been studied in workers exposed to phthalic anhydride (PA), methyltetrahydrophthalic anhydride (MTHPA), hexahydrophthalic anhydride (HHPA), and methylhexahydrophthalic anhydride (MHHPA). HSA conjugates of PA, MTHPA, HHPA, MHHPA, and maleic anhydride (MA) have been prepared and used in the tests. The hapten densities (HD) of the conjugates were varied by different molar ratios of hapten and macromolecule in the preparative procedure. Skin prick reactions to MTHPA-HSA increased with rising HD over the range 6-13 mol/mol. The achieved HD was tested by spectrometric and gas chromatographic methods. In RAST of IgE antibodies MTHPA-HSA with HD six and 25 showed significantly lower bindings than conjugates with intermediate HD. There was a good correlation between skin prick tests and RAST. Of 234 workers tested [MTHPA (n = 145), and HHPA (n = 89)], 45 had a skin prick reaction greater than or equal to 50% of the histamine reaction (1 mg/ml). All but two of these were RAST positive (RAST value greater than 0.3%; 0.3% upper range in 147 controls; MTHPA, n = 63; HHPA, n = 84). Nine RAST positive workers had no obvious skin prick reaction. However, their RAST values were low (less than 0.8%). In exposed workers, the ELISA value of specific IgG antibodies to MTHPA-HSA showed optimal values when tested with the HD 13 conjugate.(ABSTRACT TRUNCATED AT 250 WORDS)
The Food and Drug Administration (FDA) is classifying AFP-L3% (alpha-fetoprotein L3 subfraction) immunological test systems into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: AFP-L3% Immunological Test Systems." The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document that will serve as the special control for the device.
In systemic lupus erythematosus, some immunologic tests quantify disease activity, enable prediction of higher risk patterns of disease, and serve as therapeutic guides. In rheumatoid arthritis, serologic phenomena are significantly associated with more severe and sustained joint disease and with visceral manifestations (vasculitides and granulomas), but they have not been useful in monitoring the course of disease or response to therapy. In other rheumatic syndromes, a variety of antinuclear specificities show promise as marker antibodies, but their prognostic and therapeutic implications remain largely unexplored.
Whether persons with multiple chemical sensitivity syndrome (MCS) have immunological abnormalities is unknown. To assess the reliability of selected immunological tests that have been hypothesized to be associated with MCS, replicate blood samples from 19 healthy volunteers, 15 persons diagnosed with MCS, and 11 persons diagnosed with autoimmune disease were analyzed in five laboratories for expression of four T-cell surface activation markers (CD25, CD26, CD38, and HLA-DR) and in four laboratories for autoantibodies (to smooth muscle, thyroid antigens, and myelin). For T-cell activation markers, the intralaboratory reproducibility was very good, with 90% of the replicates analyzed in the same laboratory differing by < or = 3%. Interlaboratory differences were statistically significant for all T-cell subsets except CD4+ cells, ranging from minor to eightfold for CD25+ subsets. Within laboratories, the date of analysis was significantly associated with the values for all cellular activation markers. Although reproducibility of autoantibodies could not be precisely assessed due to the rarity of abnormal results, there were inconsistencies across laboratories. The effect of shipping on all measurements, while sometimes statistically significant, was very small. These results support the reliability of fresh and shipped samples for detecting large (but perhaps not small) differences between groups of donors in the T-cell subsets tested. When comparing markers that are not well standardized, it may be important to distribute samples from different study groups evenly over time.
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