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Diagnosis and prognosis in colon cancer based on a profile in immune reactivity.

An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.

Adult↗

Inflammatory myopathies--a clinicopathologic study.

In this study, clinical, histopathological and immunological profiles were analysed in ten patients with inflammatory myopathies. Polymyositis and dermatomyositis were more common than other forms of inflammatory myopathies. The pathogenetic mechanisms and distinguishing histopathological and immunological profiles between polymyositis and dermatomyositis have been highlighted.

Adolescent↗

Gluten sensitivity masquerading as systemic lupus erythematosus.

CASE REPORTS: Three patients are described whose original presentation and immunological profile led to the erroneous diagnosis of systemic lupus erythematosus. The correct diagnosis of gluten sensitivity was made after years of treatment with steroids and other immunosuppressive drugs. CONCLUSIONS: The immunological profile of IgA deficiency and/or raised double stranded DNA in the absence of antinuclear factor together with raised inflammatory markers and symptoms suggestive of an immune diathesis should alert the physician to the possibility of gluten sensitivity. The presence of an enteropathy is no longer a prerequisite for the diagnosis of gluten sensitivity, which can solely present with extraintestinal symptoms and signs. Knowledge of the diverse manifestations of gluten sensitivity is essential in avoiding such misdiagnosis.

Autoantibodies↗

Depressed host immunity in a case of metachronous primary uterine papillary serous carcinoma and non-Hodgkin's lymphoma.

Metachronous primary malignant tumors of uterine papillary serous carcinoma (UPSC) and non-Hodgkin's lymphoma (NHL) are rare. UPSC is a clinically aggressive and morphologically distinctive variant of endometrial carcinoma. We describe the clinical features of a 63-year-old patient with UPSC that was found 2 years after chemotherapy for malignant lymphoma of neck, stage IV and 5 months after radiation therapy for recurrence. This patient had undergone staging surgery and postoperative radiation for UPSC. One month after completion of radiotherapy, the patient expired due to persistence of the disease. The association between host immunity and UPSC is rarely described in the literature. Immunological profiles of this patient, with compositional changes of natural killer, B, and T cell, dramatically altered the percentage of CD4(+) T cell, CD8(+) T cell, and CD4/CD8 ratio, signifying depressed host immunity. Immunological profile of this patient stressed the issue of depressed host immunity and associated malignancies.

Carcinoma, Papillary↗

Can repeated plasma donation by asymptomatic HIV-infected individuals delay the onset of AIDS?

Healthy HIV-positive regular donors of plasma in a programme of passive immunotherapy for AIDS patients were studied over a period of about two years. None developed symptoms of clinical progression; most seemed to make substantial gains of CD4 cells by comparison with asymptomatic individuals who were not donating. The effects of donation did not seem to diminish with repetition, and donor CD4 counts tended towards stabilizing within normal limits. Asymptomatic HIV-positive individuals were compared immunologically with 'normals' and people with AIDS, using a battery of 25 measurements on peripheral blood. The immunological profiles of donor and non-donor asymptomatics, indistinguishable at the start, became dissimilar: donors' profiles resembled AIDS less, non-donors became less like 'normal' and a few non-donor results could not be distinguished from AIDS. Improvement in the CD4 counts and amelioration of the immunological profile in donors provide prima facie evidence that plasmapheresis may be therapeutic for asymptomatic HIV-positive people. Further studies are justified.

Acquired Immunodeficiency Syndrome↗

Radioimmunoassay for the antifreeze polypeptides of the winter flounder: seasonal profile and immunological cross-reactivity with other fish antifreezes.

The polymerization of winter flounder antifreeze polypeptide (AFP) with glutaraldehyde to increase its antigenicity and the conjugation of the AFP to bovine serum albumin so that the AFP could carry a radioiodine label have allowed the development of a convenient and reliable radioimmunoassay (RIA) for the antifreeze. A seasonal concentration profile of serum AFP as determined by the RIA corresponded closely with its activity profile. Winter serum concentrations of AFP measured by the RIA (7-11 mg/mL) agreed well with antifreeze recovery from Sephadex G-75 chromatography of serum (6-10 mg/mL), but less so with concentration estimates reported from activity measurements (12-25 mg/mL) (Petzel, D. H., Reisman, H. M. & DeVries, A. L. (1980) J. Exp. Zool. 211, 63-69). A small but measurable immunological cross-reactivity was detected between the antiflounder AFP and other fish antifreeze polypeptides. Such cross-reactivity was quite unexpected considering the large compositional and structural differences among the various AFP and its significance remains unclear.

Animals↗

Immunophenotypic spectrum of plasma cell leukemia.

Four cases of plasma cell leukemia (PCL) are reported that illustrate the variable immunotype of this disorder in contrast with the immunologic profile described for normal B-cell maturation and typical multiple myeloma (MM). Mature B-lymphocytes express B1 antigen (Ag) and surface immunoglobulin (SIg) whereas maturation to the plasma cell stage is accompanied by loss of these immunologic markers and expression of T10 Ag, plasma cell Ag (PCA), and cytoplasmic immunoglobulin (CIg). Plasma cells from patients with MM have previously been found to express the immunophenotype of normal plasma cells. In contrast, none of the four cases reported here express an immunologic profile typical for specific B-cell differentiation stages. Only one of four cases was strongly positive for PCA but additionally expressed B1 Ag and SIg. Of the remaining three cases, all expressed T10 Ag and CIg; two cases also expressed SIg, weak PCA, and B1 Ag. All four cases were monoclonal for lambda light chains and negative for common ALL Ag (CALLA). The variable expression of mature B-cell markers and plasma cell markers demonstrates the immunophenotypic spectrum of PCL; the prognostic significance of this heterogeneity needs to be more closely examined.

Adult↗

Immunological studies of children with anaphylactoid purpura.

Anaphylactoid purpura is a small-vessel, vasculitic disease of unknown etiology, but it is thought to be caused by an immunoglobulin-mediated inflammatory process. To study the immunological profiles of local anaphylactoid purpura patients, during the period from October 1996 to October 1997 with 17 patients, (6 boys and 11 girls), (aged 3 years to 17 years, mean age: 7.9 years), with anaphylactoid purpura who visited National Taiwan University Hospital. Immunological studies were performed in 17 patients and 20 age-matched healthy controls. Higher C3 was noted in patients (126.2 +/- 26.7 mg/dL) than in the control group (116.1 +/- 16.7 mg/dL), although without statistical significance (P = 0.307). C4 levels of patients were significantly higher in patients than control group (38.6 +/- 13.4 v.s. 23.7 +/- 6.9 mg/dL), P < 0.001). There were no significant differences in the IgG and IgM levels between patient and control groups. In contrast, the IgA levels of patient were significantly higher than that control groups (293.1 +/- 102.9 v.s. 179.8 +/- 71.0 mg/dL, P = 0.001). The serum level of TGF-beta 1 of patients was higher than that of the control group although not statistically significant (44.1 +/- 27.3 v.s. 29.9 +/- 19.0 ng/mL, p = 0.067). A significantly higher percentage of T cells was noted in anaphylactoid purpura patients than controls (71.5 +/- 9.2% v.s. 65.0 +/- 6.3%, P = 0.016). However, no significant difference was found in other subpopulations of lymphocytes. These basic immunological profiles may be helpful for further work on the pathogenesis of anaphylactoid purpura.

Adolescent↗

Identification of immune response correlates for protection against bovine tuberculosis.

Identification of an immune response correlate for protection against bovine tuberculosis would greatly facilitate the rational development of an effective vaccine. However, finding such a correlate has been a daunting task. Vaccination/challenge studies in cattle provide an ideal platform to compare induction of immune response parameters following vaccination and challenge, and assess the correlation of these parameters with protection. Protection against tuberculosis requires a Th 1-type cell-mediated immune response and induction of an antigen-specific interferon-gamma (IFN-gamma) response was the logical first choice in an investigation to identify an immune response correlate for protection. Calf vaccination studies showed that the subcutaneous injection of BCG vaccine induced significant protection against experimental challenge with Mycobacterium bovis. This protection was associated with strong whole blood IFN-gamma responses to bovine PPD 2-4 weeks after vaccination, but within the BCG-vaccinated groups, these responses were not correlated with protection. Use of a variety of vaccination strategies has shown that IFN-gamma responses in isolation were not necessarily associated with protection and concurrent IL-4 mRNA expression or antibody responses could also be induced. Collation of an immunological profile may be more informative than a study of individual cytokines. An indication of vaccine efficacy can be provided by the study of immune responses following challenge of the calves with M. bovis. IFN-gamma responses to ESAT-6, antibody responses following tuberculin skin testing and antigen-specific IL-4 mRNA expression all correlated with the severity of disease and indirectly provided an indication of protection. Future studies should be directed towards obtaining immunological profiles of calves following vaccination using techniques such as DNA microarray analysis, measurement of cytokine mRNA expression by real-time PCR, protein profiling by SELDI-TOF mass spectrometry as well as determining cytokine production by specific T cell sub-sets in individual protected animals.

Animals↗

Seroepidemiological and clinical study of Chagas' disease in Nicaragua.

With the aim of determining the prevalence, immunological profile, and knowing the electrocardiographic alterations, a clinical and seroepidemiological study of Chagas' disease was performed in three rural settlements located at the North, East and West of Nicaragua. Anti T. cruzi antibodies were searched by indirect immunofluorescence (IFI) and hemagglutination (IHA) in a total of 803 subjects. Seropositives and the same number of seronegatives, matched by age and sex, were included in a case-control design for the electrocardiographic assessment. Antibody prevalence was 13.1, 4.3 and 3.2% in the respective settlements. In the first two the immunological profile corresponds to that of an endemic zone of long standing, were transmission has decreased, and in the third the pattern is of a zone under control. Electrocardiographic changes compatible with Chagas' disease were found in seropositive individuals, but difference with control group was not statistically significant. It is concluded that the disease is endemic in the three settlements and the clinical aspect requires further evaluation, including additional cardiologic techniques.

Adolescent↗

Relationship between occupational risk factors and severity markers of systemic sclerosis.

OBJECTIVE: To investigate a potential association between occupational risk factors and severity markers of systemic sclerosis (SSc) defined by diffuse cutaneous extent, pulmonary involvement, and immunologic profile, i.e., presence of antitopoisomerase I antibody (anti-topo I). METHODS: Occupational exposures were assessed in 105 patients with SSc from 1998 to 2002. Exposures to silica dust, welding fumes, solvents, and epoxy resins were investigated. A group of 39 exposed SSc patients and a group of 66 unexposed ones were identified and compared according to severity markers of SSc. The stage of cutaneous extent was defined according to the classification of Leroy, as limited scleroderma (lSSc) or diffuse scleroderma (dSSc). Respiratory status was defined by pulmonary function tests and high resolution computed tomography. Immunological profile was determined by the presence of anti-topo I or anticentromere antibodies (ACA). Statistical relationships between occupational exposures and severity markers of SSc were evaluated using a multiple correspondence analysis and Fisher's exact test. RESULTS: Diffuse scleroderma affected mainly patients exposed during their occupational life to toxic agents. There were significant or close to significant associations between toxic exposure and dSSc (p = 0.06), pulmonary involvement (p = 0.10), and negative ACA (p = 0.03). The most incriminated products seemed to be epoxy resins (p = 0.06), white spirit (p = 0.07), aromatic solvents (p = 0.07), and silica coupled to welding fumes (p = 0.10). CONCLUSION: Our results indicate that occupational toxic factors have an influence on the severity of SSc.

Adult↗

Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis.

The ineffective immune response in patients with the acquired immune deficiency syndrome (AIDS) contributes to severe and widespread infections and unrestricted growth by certain tumors. To determine whether monocyte dysfunction contributes to this immunosuppressed condition, we investigated monocyte chemotaxis in patients with AIDS. Using three different chemotactic stimuli, N-formylmethionylleucylphenylalanine, lymphocyte-derived chemotactic factor, and C5a des Arg, we studied the chemotactic responses of monocytes from seven homosexual men with AIDS, three homosexuals with lymphadenopathy and an abnormal immunological profile, seven healthy homosexual men, and 23 heterosexual control individuals. Monocytes from each of the AIDS patients with Kaposi's sarcoma and/or opportunistic infection exhibited a marked reduction in chemotaxis to all stimuli compared with the healthy control subjects. The reduced chemotactic responses were observed over a wide range of concentrations for each stimulus. Monocytes from AIDS patients who had clinically apparent opportunistic infection(s) exhibited a greater reduction in monocyte migration to all three stimuli than monocytes from the AIDS patient with only Kaposi's sarcoma. Monocytes from each of three homosexuals with lymphadenopathy and an abnormal immunological profile exhibited decreased chemotactic responses that were intermediate between those of the AIDS patients and the healthy heterosexual control subjects. In contrast to these findings, monocytes from each of seven healthy homosexuals exhibited normal chemotactic responses to the same stimuli. In addition, monocytes from AIDS patients exhibited reduced chemotaxis to soluble products of Giardia lamblia, one of several protozoan parasites prevalent in AIDS patients. Thus the immune abnormality in AIDS, previously thought to involve only the T-, B-, and natural killer lymphocytes, extends to the monocyte-macrophage. Defective monocyte migratory function may contribute to the depressed inflammatory response to certain organisms and to the apparent unrestricted growth of certain neoplasms in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

[Details of the evolution of the influenza epidemic process in the city of Bucharest in 1974].

The present paper reports on the results of a complex epidemiologic survey of the epidemiologic potential of influenza in Bucharest in 1974, conducted on the basis of a complete, unitary methodology including; (a) Dynamic survey of the morbidity and mortality from influenza, with statistical-mathematical processing of the data per age group and total population; (b) Monthly sero-epidemiologic survey of the antiinfluenza immunologic profile of the population, determined in lots of 540 sera (annual total 7020 serum samples), with statistical-mathematical processing of the serograms; (c) Serodynamic determinations of 67 paired serum smaples collected from patients presenting influenza syndromes during ascension of the epidemic morbidity from influenza; (d) Complex epidemiologic surveys in representative influenza foci in children, adolescent and adult communities. Based upon the result obtained the authors discuss the evolutive particularities of the epidemiologic process in Bucharest, particularly during the epidemic ascension of the first trimester of 1974, caused by the intensified circulation of influenza virus type B. The orientative value of certain elements for the epidemiologic prognosis is emphasized, such as: the immunologic profile of the population per age group with regard to the circulating influenza virus strains (autochtonous or imported strains), active control of the incidence of influenza in communities (technical schools etc.) or enterprises with a large number of employees, laboratory etiologic determinations in cases of a clinical diagnosis of influenza in a preepidemic season. The authors' ten years experience in the active survey of the active epidemiologic potential of influenza in the town of Bucharest shows that the methodology applied was efficient both for scientific assessing of the epidemiologic situation and for an orientation in the choice of preventive and control measures.

Adolescent↗

Primary Sjogren's syndrome: rarity in India.

OBJECTIVE: Primary Sjogren's syndrome (SS) is rarely reported from India. We have studied the clinical spectrum and immunological profile of patients with primary SS. METHODS: A prospective analysis of patients with primary Sjogren's syndrome fulfilling San Francisco criteria, seen at our clinic in the last 10 years was carried out. RESULTS: The study included 26 patients, 21 being women. The presenting symptoms included dry eyes, dry mouth, and arthritis/arthralgia. Extra-glandular manifestations were glomerulonephritis, vasculitis, renal tubular acidosis and peripheral neuropathy. The important laboratory abnormalities were hypergammaglobulinaemia (16/20), antinuclear antibodies (18/26), anti-La (11/19) and anti-Ro (10/19). Minor salivary gland provided a definitive diagnosis in 16/26 (60%). CONCLUSION: The prevalence of primary Sjogren's syndrome is rare even in tertiary care rheumatology clinics. The clinical and immunological profile as seen here is similar to that reported in Western countries.

Adult↗

Comparative analysis of immunocritical melanoma markers in the mouse melanoma cell lines B16, K1735 and S91-M3.

The mouse melanoma cell lines B16, K1735 and Cloudman S91-M3 (and various sublines) are frequently used as melanoma models. Extensive comparative data of their immunological features are not available. In order to define the immunological profiles of these cell lines, relevant tumour markers were studied. S91-M3 melanoma cells constitutively expressed high levels of major histocompatibility complex (MHC) I, in contrast to K1735-M2 and B16-F1 cells. MHC II expression was restricted to B16-F1 cells following interferon-gamma treatment. Tyrosinase, tyrosinase-related protein-2 and gp100 were detected in B16-F1 and S91-M3 cells, but not in K1735-M2 cells. Constitutive surface expression and secretion of intercellular adhesion molecule-1 was found on S91-M3 cells. No substantial secretion of interleukin-10 could be detected. In contrast, low levels of latent transforming growth factor-beta were found in the cell supernatants of B16-F1 and K1735-M2 cells. The expression pattern of Fas, FasL and FLICE inhibitory protein was comparable in all three cell lines. Thus our findings indicate that each cell line presents a characteristic immunological profile, confirming that B16-F1 is an appropriate murine tumour model for tumours with low levels of MHC I but expressing melanoma-associated antigens. S91-M3 represents a complementary, more immunogenic model. In contrast, K1735-M2 does not seem to be an appropriate model for melanoma.

Animals↗

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis-cirrhosis, and HIV-1 infection by platelet and serum immunological measurements.

A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2.8-, 5.6- and 5.8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients: platelet C3C4 was 3.2-, 4.8- and 4.5-fold higher respectively; platelet IgM was 2.2-, 3.7- and 3.8-fold higher respectively; serum PEG-IC levels were 4.2-, 4.8- and 2.1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r = 0.5, P < 0.04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r = 0.7, P < 0.04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.

Acquired Immunodeficiency Syndrome↗

Immunologic tolerability profile of celecoxib.

Celecoxib is primarily an inhibitor of cyclooxygenase (COX) 2 and, at therapeutic concentrations in humans, does not inhibit the COX-1 isoenzyme. The present meta-analyses explore the incidence of allergic reactions with celecoxib in patients in the North American and international arthritis trials, in patients with a history of hypersensitivity reactions to sulfonamides, and in patients receiving medications containing sulfonamides. Data were obtained from 11,008 patients in 14 double-masked trials of celecoxib in arthritis ranging from 4 to 24 weeks in duration. Results demonstrate that the incidence of allergic reactions with celecoxib was not statistically different from that seen with placebo or active comparators (nonsteroidal anti-inflammatory drugs [NSAIDs]) when data from the entire cohort were analyzed. The subset of patients with a history of sulfonamide hypersensitivity reactions had a 3-fold to 6-fold higher incidence of dermatologic reactions than did the entire arthritis trial cohort. Although dermatologic reactions occurred with greater frequency in patients with a history of sulfonamide hypersensitivity, the trend was consistent across all 3 treatment groups (celecoxib, NSAIDs, and placebo). According to these data and structural and metabolic differences between sulfonamides, the potential for cross-allergenicity between celecoxib and other sulfonamide-containing medications appears comparable to that of placebo and nonsulfonamide-containing NSAIDs. Additionally, the risk of allergic reactions with celecoxib appears comparable to that of placebo and comparator NSAIDs. Prospective trials are needed to confirm these findings.

Anti-Inflammatory Agents, Non-Steroidal↗

Immunological tumour profile: organ-specific carcinoma diagnosis in patients employing the macrophage electrophoretic mobility test.

The macrophage electrophoretic mobility (MEM) test provides a highly sensitive in vitro technique for the detection of cell-mediated immunity in man. The principle involved is the lymphokine-mediated reduction of the negative surface charge of guinea pig macrophages shown by the slowing of the macrophages during cell electrophoresis. Lymphocytes from 162 patients were tested by MEM. They were exposed to a battery of KCl extracts from normal and malignant human tissues, to encephalitogenic protein (EP), to carcinoembryonic antigen (CEA), and to thyroglobulin. Variable lymphocyte responses to EP, CEA and KCl extracts from different cancers gave MEM reaction profiles common to patients with carcinomas of the same organ origin.

Antigens, Neoplasm↗