Immune complex disease in experimental animals and man.
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Aleutian Mink Disease↗
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The rapidly changing nature of acute immune complex disease.
Antibody was measured in acute serum sickness with a modified ABC Farr test. Under the conditions of antigen excess which were employed in this test, antibody could be detected before antigen was eliminated from the circulation. This approach made it possible to directly measure the ratio of antigen to antibody in the serum. The antigen/antibody ratio changed daily. The immunologic conditions could be divided into three phases. In phase I the serum antigen/antibody ratio showed great antigen excess, with values of 2:1 or greater. Cold-insoluble complexes were not seen in this phase, and antigen was cleared slowly from the circulation. The serum antigen/antibody ratio in phase II varied from 1:1 to 1:20 corresponding to conditions of slight antigen excess. Partial cold insolubility of circulating complexes was observed. The rate of antigen clearance increased during this phase. Phase III began just before antigen was completely eliminated. The serum antigen/antibody ratio was 1:40 or less. At this time the complexes in the circulation exhibited marked cold insolubility, and the rate of antigen clearance was extremely rapid.
Acute Disease↗
Immune complex disease associated with Epstein-Barr virus infectious mononucleosis.
We describe a patient with immune complex-mediated glomerulonephritis and leukocytoclastic vasculitis associated with Epstein-Barr virus (EBV) infectious mononucleosis. The patient required hemodialysis and has residual hypertension. This case implicates acute EBV infection as a cause of immune complex-mediated glomerulonephritis.
Acute Disease↗
Canine immune complex diseases.
Though not conclusive, our primary findings indicate that a feature common to many of our tumor and ICD patients is depressed cortisol production. Additionally, the response to ACTH adrenal cortex stimulation tests, at 2-hour intervals between rest and stimulation, have ranged from negative to substantially less than would be expected in normal subjects. Peripheral plasma cortisol values for dogs, at rest and 2 hours after ACTH stimulation, respectively, have been reported as 2-10 and 25-30 mug/dl, 3-8 and 7.5-18 mug/dl, and 1-12.5 and 9.5-22 mug/dl. For representative patients, our resting values have been 1.2-5.2 mug/dl, vs 1.2-7.6 mug after ACTH stimulation (Table 2). Altogether we have studied 42 cases in detail, and we feel that a post-ACTH level of 8.0 mug/dl or less is a conservative indication of adrenocortical insufficiency; all levels have been between 1 and 8 mug/dl. We believe these low cortisol levels indicate either a genetically-induced adrenal cortical insufficiency (evident at 2 months to 1 year of age) or an immune complex adrenal cortical suppression (occurring after 1 year of age in association with other immunodeficiency disorders). Our studies demonstrate a need for biphasic therapy. We have found it necessary to not only initiate cortisone acetate therapy to support the deficient adrenal cortical secretion, but also use other immunosuppressive drugs to control the ICD. If the target organ has been suppressed or destroyed, the need for supplementation is obvious. However, other immune-injury moieties must be suppressed also, eg, ANA, anti-IgG antibodies, etc.
Animals↗
Pathophysiologicl aspects of immune complex diseases part i. interaction with plasma enzyme systems, cell membranes and the immune response.
Immune complexes (IC) may be pathophysiologically active in correlation with the nature and size of the antigen, the type and the quality of the antibody, and the concentration of both. Those parameters are decisive for the composition and the lattice structure of IC. Pathogenic effects are induced: by complement activation and generation of biologically active C' split products via the classical and the alternative pathway, by interaction with Fc and complement receptors resulting in exocytosis of lysosomal contents including degradative enzymes, cationic proteins, vasoactive amines and mediators effective on lymphocytes and macrophages; by direct and indirect activation of the Hageman factor followed by stimulation of the kinin, coagulation and fibrinolysis system; and by modulation of the immune response via the afferent and the efferent branch. All those mechanisms seen to be involved in the induction of lesions along the vessel wall in the various privileged organs.
Antibody Formation↗
Mucocutaneous lymph node syndrome. Review of a recently described disease complex.
Mucocutaneous lymph node syndrome (MLNS) has been accepted in Japan as a newly recognized disease affecting most frequently patients under 5 years of age. It is now apparent that the syndrome, having been defined, is also recognized with increasing frequency in the continental United States and Canada in children of non-Japanese ancestry. MLNS is characterized by (1) fever, (2) bilateral congestion of the conjunctivae, (3) changes in the oral cavity, consisting of strawberry tongue, erythema of the oral mucosa, and sicca of the lips, (4) indurative edema and erythema of the hands and feet followed by desquamation of the fingertips, (5) polymorphous exanthema, and (6) cervical lymphadenopathy. The clinical signs and symptoms are somewhat reminiscent of other related conditions. To prevent potentially fatal cardiac complications associated with MLNS, prompt and accurate diagnosis is imperative so that the patient may be referred to a physician for careful monitoring during convalescence.
Canada↗
Pathological and radiological changes in resected lung specimens in Mycobacterium avium intracellulare complex disease.
The present study was designed to evaluate the pathological and immunohistochemical findings of Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed in five cases with positive cultures for MAC in whom lung resections were performed between January 1989 and December 1996. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria defined by the American Thoracic Society. In addition, MAC was cultured from all of the five lung specimens. Pathological and immunohistochemical findings as well as chest computed tomography (CT) findings were evaluated in these five patients. Pathological findings of bronchiectasis, bronchiolitis, centrilobular lesion, consolidation, cavity wall and nodules were demonstrated, respectively, in relation to chest CT findings. Extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; 2) myofibroblasts extensively infiltrating the cavity wall; and 3) B-cells detected in aggregates in the vicinity of the epithelioid granulomas. This study identified pathological and immunohistochemical characteristics of Mycobacterium avium complex infection relative to chest computed tomography findings and allowed the conclusion that bronchiectasis and bronchiolitis were definitely caused by Mycobacterium avium complex infection.
Adult↗
Construction of endophenotypes for complex diseases in the presence of heterogeneity.
Endophenotypes such as behavior disorders have been increasingly adopted in genetic studies for complex traits. For efficient gene mapping, it is essential that an endophenotype is associated with the disease of interest and is inheritable or co-segregating within families. In this study, we proposed a strategy to construct endophenotypes to analyze the Genetic Analysis Workshop 14 simulated dataset. Initially, generalized estimating equation models were employed to identify phenotypes that were correlated to the disease (affected status) in combination with the family structures in data. Endophenotypes were then constructed with consideration of heterogeneity as functions of the identified phenotypes. Genome scans on the constructed endophenotypes were carried out using family-based association analysis. For comparison, genome scans were also performed with the original affected status. The family-based association analysis using the endophenotypes correctly identified the same susceptible gene in about 80 of the 100 replicates.
Chromosomes, Human, Pair 3↗
The microbiological and clinical effects of combined therapy according to guidelines on the treatment of pulmonary Mycobacterium avium complex disease in Japan - including a follow-up study.
BACKGROUND: The difficulty of treatment for pulmonary Mycobacterium avium complex (MAC) in Japan. OBJECTIVES: To investigate the clinical and microbiological effects of treatment according to the guidelines proposed by the American Thoracic Society and the Japanese Society for Tuberculosis and prospective follow-up studies after the completion of treatment of patients with pulmonary MAC disease. METHODS: Analysis of the microbiological effects with regard to sputum conversion rate and the sputum relapsing rate and the clinical effects with regard to clinical symptoms and radiological findings for patients with pulmonary MAC disease treated with a regimen consisting of rifampicin, ethambutol, streptomycin, and clarithromycin over 24 months and follow-up over 12 months. RESULTS: Sixty-five patients with pulmonary MAC disease were enrolled in this trial. In 39 patients, negative sputum conversion was observed within 6 months after the initiation of this regimen, 16 relapsed, and 20 experienced clinical worsening within 1 year after the completion of treatment. Although retreatment with the same regimen or a regimen including new quinolones was carried out for these patients, we could not achieve negative sputum conversion and/or clinical improvement. CONCLUSIONS: We believe that the dose of clarithromycin for pulmonary MAC disease may be increased and recommend surgery for patients with a localized lesion at early-stage MAC disease to prevent a high rate of relapse.
Antitubercular Agents↗
Early manifestations of disseminated Mycobacterium avium complex disease: a prospective evaluation.
A nested case-control study was conducted in two trials of prophylaxis for Mycobacterium avium complex (MAC) infection to describe the specific signs, symptoms, and laboratory abnormalities of MAC disease in AIDS. Patients had < or =200/mm3 CD4 cells and a prior AIDS-defining illness. Of 571 patients, 102 (17.9%) developed MAC bacteremia during a mean follow-up of 256 days. Among cases of MAC disease, 90 were compared with 180 matched controls. Patients with MAC disease were more likely than controls to have lower weights (66.3 vs. 71.1 kg, P = .001) and Karnofsky scores (74.3 vs. 84.4, P < .001); a higher proportion had fever (48% vs. 26%, P = .003), abdominal pain (23% vs. 13%, P =.05), decreased hemoglobin levels (10.9 vs. 12.1 g/dL, P < .001), and elevated alkaline phosphatase (203 vs. 138 U/L, P=.04) and lactate dehydrogenase (334 vs. 280 U/L, P = .02) levels. Characteristics of MAC disease that occurred before bacteremia were weight loss (3 months prior), fever (2 months), and anemia and elevated lactate dehydrogenase (1 month). These data suggest that patients have symptomatic MAC disease for several months prior to the occurrence of bacteremia.
Adult↗
Transmissible spongiform encephalopathies: a family of etiologically complex diseases--a review.
The upsurge of 'mad cow disease' with its human implications has raised the problem of the etiological mechanisms and the similarities or differences underlying the family of transmissible spongiform encephalopathies. Structural properties of prions are reviewed in connection with their natural distribution and functions, factors of transmissibility and mechanisms of pathogenicity. Polymorphism is examined in relation to disease phenotype variants. The role of oxidative factors is emphasized, while raising complexity about the role of copper ions. Further investigation directions are suggested.
Animals↗
Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence.
To analyze candidate genes and establish complex genotype-phenotype relationships against a background of high natural genome sequence variability, we have developed approaches to (i) compare candidate gene sequence information in multiple individuals; (ii) predict haplotypes from numerous variants; and (iii) classify haplotypes and identify specific sequence variants, or combinations of variants (pattern), associated with the phenotype. Using the human mu opioid receptor gene (OPRM1) as a model system, we have combined these approaches to test a potential role of OPRM1 in substance (heroin/cocaine) dependence. All known functionally relevant regions of this prime candidate gene were analyzed by multiplex sequence comparison in 250 cases and controls; 43 variants were identified and 52 different haplotypes predicted in the subgroup of 172 African-Americans. These haplotypes were classified by similarity clustering into two functionally related categories, one of which was significantly more frequent in substance-dependent individuals. Common to this category was a characteristic pattern of sequence variants [-1793T-->A, -1699Tins, -1320A-->G, -111C-->T, +17C-->T (A6V)], which was associated with substance dependence. This study provides an example of approaches that have been successfully applied to the establishment of complex genotype-phenotype relationships in the presence of abundant DNA sequence variation.
Adult↗
Transferrin-immune complex disease.
A 71-year-old woman showed a highly unusual pattern of iron distribution in the organism which was associated with iron overload. The hallmark of this disease was an extreme hypersiderinemia, the serum iron reaching about 800 mug/100 ml. There was a pigment cirrhosis of the liver, bronzed skin containing hemosiderin, and diabetes mellitus. Paradoxically, hemosiderin was not detectable in bone marrow macrophages, sideroblasts and erythrocytes were reduced, and there was a decrease in radioiron utilization of erythropoiesis, thus indicating insufficient iron supply. The pathogenesis of this disorder based on the formation of an autoantibody with specificity for transferrin thus producing a circulating immune complex which bound the majority of serum iron. Immunosuppression achieved a partial remission including a recovery of the patient's general state, a rise in free transferrin, a decrease in serum iron, disappearance of hemosiderin in the liver, and a rise in erythrocyte production.
Aged↗
A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans.
In recent years, the number of studies focusing on the genetic basis of common disorders with a complex mode of inheritance, in which multiple genes of small effect are involved, has been steadily increasing. An improved methodology to identify the cumulative contribution of several polymorphous genes would accelerate our understanding of their importance in disease susceptibility and our ability to develop new treatments. A critical bottleneck is the inability of standard statistical approaches, developed for relatively modest predictor sets, to achieve power in the face of the enormous growth in our knowledge of genomics. The inability is due to the combinatorial complexity arising in searches for multiple interacting genes. Similar "curse of dimensionality" problems have arisen in other fields, and Bayesian statistical approaches coupled to Markov chain Monte Carlo (MCMC) techniques have led to significant improvements in understanding. We present here an algorithm, APSampler, for the exploration of potential combinations of allelic variations positively or negatively associated with a disease or with a phenotype. The algorithm relies on the rank comparison of phenotype for individuals with and without specific patterns (i.e., combinations of allelic variants) isolated in genetic backgrounds matched for the remaining significant patterns. It constructs a Markov chain to sample only potentially significant variants, minimizing the potential of large data sets to overwhelm the search. We tested APSampler on a simulated data set and on a case-control MS (multiple sclerosis) study for ethnic Russians. For the simulated data, the algorithm identified all the phenotype-associated allele combinations coded into the data and, for the MS data, it replicated the previously known findings.
Algorithms↗
Canine seborrheic disease complex.
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Animals↗
ON SIALECTASIS AND BENIGN LYMPHOSIALDENOPATHY. (THE PYOGENIC PAROTITIS, GOUGEROT-SJOEGREN'S SYNDROME, MIKULICZ'S DISEASE COMPLEX.) A TEN-YEAR STUDY.
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Autoimmune Diseases↗
THE BOVINE VIRAL DIARRHEA-MUCOSAL DISEASE COMPLEX.
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Animals↗
Immune complex disease. VII. Experimental mesangiopathic glomerulonephritis produced by chronic immunization with thyroglobulin.
Immunohistologic and electron microscipic studies were performed on the kidneys of rabbits given daily intravenous injections of porcine thyroglobulin in amounts adjusted to the immune response of the individual rabbits. Glomerular lesions were restricted to the mesangium, were characterized by varying degrees of proliferation of mesangial cells and increase of mesangial matrix, and were accompanied by accumulations of rabbit immunoglobulins, C3, and porcine thyroglobulin. Electron-dense deposits were localized to the mesangium and the adjacent subendothelial space. Less than 10 per cent of the animals with mesangila lesions developed obvious impairment of glomerular function. Thyroglobulin-containing immune complexes were found to be rapidly removed from the mesangium, so that overloading of the mesangium and consequent accumulation of complexes in the adjacent capillary loops could not occur. Thus, the results provide further evidence that when immune complex deposition is restricted to the mesangium, relatively little interference with glomerular function results. This situation is paralleled in man by the lesions of subclinical lupus nephritis, chance proteinuria and hematuria, and the early lesions of Berger's disease.
Animals↗