[Silicone prostheses one more time--are they justified?].
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Breast Implants↗
Biomedical subjects
O J Mellbye
Publications and source records attributed to O J Mellbye.
Immunoglobulin prolongs survival of pig kidneys perfused ex vivo with human blood.
Intravenous immunoglobulin (IVIG) (Octagam), was used to determine the effect on hyperacute rejection in an ex vivo xenograft model. Six pig kidneys were perfused with IVIG and fresh human AB blood, and six control pig kidneys were simultaneously perfused with albumin and blood from the same donation. The survival of the IVIG-perfused xenografts (median, 6.5 h) was significantly (P = 0.03) longer than the albumin-perfused xenografts (median, 3.5 h). Complement was activated in both groups. The administration of IVIG to the perfused blood resulted in immediate and significantly higher complement activation in the fluid phase as compared with the albumin group. At rejection the fluid phase complement activation was higher in the IVIG group than in the albumin group for C1rs/C1inh complexes, C4bc, Bb and TCC. At the time of rejection both the albumin and the IVIG group demonstrated interstitial tubular haemorrhage, vasculitis or necrosis of glomerular capillaries and glomerular microthrombi. IgM, C1q, C3c, C4 and fibrin were located in arteries and glomeruli and IgG in the interstitium in both groups at rejection. The fluid phase findings are consistent with a modulatory effect of IVIG on complement activation by deviating the classical pathway activation towards the fluid phase. The prolonged survival of the IVIG-perfused kidneys suggests that IVIG may be useful to dampen hyperacute rejection.
Animals↗
Chronic arthritis and gamma heavy chain disease: coincidence or pathogenic link?
In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy. Her gamma heavy chain disease had a benign course, requiring no specific therapy for 5 years. In 1996, however, her lymphoproliferative disorder underwent a more malignant course, with renal and cardiac failure and increasing articular problems, requiring treatment with melphalan and prednisolone, following the protocol for myelomatosis. Laboratory studies revealed a monoclonal component in serum and urine. consistent with dimers of gamma-chains of the gamma3 subclass, but with a smaller molecular mass than normal gamma3-chains, suggesting molecular aberrations as consistently observed in this disorder. Massive localization of plasma cells and blasts with cytoplasmic or cell membrane staining for gamma3-chains, but no staining for kappa or lambda light chains, was observed by immunohistochemical studies of tissue specimens from bone marrow as well as affected synovial tissue. Large amounts of extracellular gamma3-chains were deposited in the synovial membrane. In addition, marked inflammatory changes with synovial cell hyperplasia were seen. Whether the present case represents primarily a gamma heavy chain deposition disease with reactive inflammatory changes in the joints, or another example of gamma heavy chain disease preceded by seronegative rheumatoid arthritis, remains elusive. Regardless, a possible pathogenic link between the two disease processes is an intriguing possibility.
Adult↗
A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency.
We present a boy with hyper-IgM syndrome with a previously not reported mutation in the CD40 ligand gene. He also had a concomitant natural killer (NK) cell deficiency. He had no CD56+ or CD16+ cells and no NK activity as determined in 4 h chromium release cytotoxicity assay. After 5 days in culture with IL-2-containing medium, however, his peripheral blood mononuclear cells lysed both NK-sensitive and NK-resistant targets, showing that he had lymphokine-activated killer cell precursors in the circulation. Due to the associated neutropenia, he was treated with granulocyte colony-stimulating factor (G-CSF) and responded well. In the same period we observed a transient increase in the number of NK cells. Isolated NK cell deficiencies are extremely rare. We suggest that the defect in our patient is part of the hyper-IgM syndrome, probably representing the phenotype of the new mutation described. Thus, it is possible that both the neutropenia and the NK cell deficiency are due to lack of growth-promoting signals normally delivered by the CD40 ligand.
CD40 Antigens↗
Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.
Overlapping features between primary sclerosing cholangitis (PSC and autoimmune hepatitis (AIH) have previously been noted. To assess systematically similarities between these disorders, we have evaluated 114 PSC patients (36 women; 78 men), all confirmed by endoscopic retrograde cholangiography (ERC), according to a scoring system proposed by The International Autoimmune Hepatitis Group for the diagnosis of AIH. The scoring system attributes positive or negative scores to the parameters sex, ratio of elevation of serum levels of alkaline phosphatase (ALP) vs. aminotransferase, serum levels of immunoglobulins and autoantibodies, viral markers, history of drug and alcohol intake, genetic factors, liver histology, and response to therapy. Two of the PSC patients (2%) obtained scores above 15 before treatment, satisfying the diagnostic criterion of "definite" AIH. Thirty-eight patients (33%) scored between 10 and 15 points and could be classified as "probable" AIH. The serum level of immunoglobulin G (IgG) was elevated in 68 patients (61% of 111 cases tested), and positive titers of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) were detected in 24 patients (22% of 111 cases tested). Thirty-five of the PSC patients (33% of 105 evaluable biopsy specimens) obtained positive scores for histological features similar to those of AIH, but the total score for histology was in the negative range in 72 patients (69%) because of the presence of biliary changes. The frequent finding of high scores in PSC patients underlines the similarities PSC may have with AIH. A modification of the scoring system, in particular by increasing the negative score for histological biliary changes, would improve its potential to discriminate between AIH and PSC.
Adolescent↗
Adhesion molecule expression and complement activation in vessel walls in synovial tissue from patients with chronic inflammatory joint disease.
Histopathology demonstrating a manifest vasculitis is a rare event in synovial tissue (ST) from patients with chronic inflammatory joint disease. As a possibly more subtle sign of a vasculitic process, complement activation in vessels in ST was studied. In the same tissues, the expression of the adhesion molecules ICAM-1 and E-selectin in vessel walls was examined, to see if the expression was related to vasculitic processes. The study was performed by use of direct immunofluorescence technique on cryostat sections of ST, using mouse monoclonal antibodies to the terminal complement complex (TCC, C5b-9), ICAM-1 and E-selectin. Expression of ICAM-1 was found in the vessel walls in all of 28 tissues tested, whereas E-selectin was found in 4 cases and TCC in 11. E-selectin and TCC were found together in only 1 tissue. The study supports the view that ICAM-1 is always, or nearly always, present in vessel walls in synovial tissue from patients with chronic inflammatory joint disease. E-selectin and TCC may also be present, but the lack of association between these two proteins suggests that the mechanism leading to a complement mediated vasculitic process is different from that causing expression of E-selectin.
Animals↗
Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses.
OBJECTIVES: To study clinical and laboratory manifestations of hereditary angio-oedema (HAE). SUBJECTS: Thirty-three affected members of a kindred of 63. RESULTS: Oedematous attacks in the skin, mucous membranes and gastrointestinal tract with fluid displacement were elicited by mental and physical stress, minor traumas, dental and surgical procedures, eruption of teeth, tonsillitis, pregnancies, and use of oestrogen-containing pills including menopausal substitution. Every adult woman with symptomatic HAE (n = 11) showed symptoms of urinary tract infections in conjunction with the attacks (P = 0.010), and also experienced more spontaneous abortions or premature labours (P = 0.037) than healthy relatives. Patients with HAE of both sexes more frequently reported heartburn or peptic ulcers (P = 0.002). Rheumatic complaints were reported by 53% of HAE patients and 12% of their unaffected relatives (P = 0.013), but biochemical screening for 18 autoantibodies and quantitation of immunoglobulins did not reveal statistically significant differences between the two groups. C3, prekallikrein, total kininogen, high molecular weight kininogen (HK), alpha-2-macroglobulin and factor XII were not significantly different in HAE patients. In contrast, levels of C1-INH and C4 were depressed and cleaved HK increased in patients compared to unaffected relatives. CONCLUSIONS: HAE manifests in a variety of ways, and may influence risk of spontaneous abortions and premature labour.
Adolescent↗
The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue.
We document here the identification of germinal centres with dark and light zones, a follicular dendritic cell network and clonal expansion in the synovium of rheumatoid arthritis patients. Synovial tissue from 24 patients suffering from rheumatoid arthritis or the polyarticular form of juvenile rheumatoid arthritis were screened for the presence of lymphoid follicles. The synovial tissues of 14 patients contained follicles and four of these had germinal centres and a follicular dendritic cell network. There was a statistically significant association between follicles in the synovium and the presence of rheumatoid factor autoantibodies in the patients' serum indicating a link between local germinal centre formation and the presence of pathological rheumatoid factors. Nucleotide sequencing of monoclonal rheumatoid factors from one of the patients' synovial tissue which contained germinal centres clearly supports the possibility that these rheumatoid factors have gone through a germinal centre reaction. While rheumatoid factors from healthy immunized donors are regulated through a tolerization mechanism which selects against replacement mutations and does not allow affinity maturation, synovial rheumatoid factors seem to lack this tolerization mechanism. The formation of germinal centres where B cells affinity mature and expand at the central site of disease in rheumatoid arthritis may explain why rheumatoid factors in rheumatoid arthritis develop into auto-aggressive antibodies.
Adolescent↗
Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet.
We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.
Adult↗
IgG subclass distribution and complement activation ability of autoantibodies to neutrophil cytoplasmic antigens (ANCA).
To study the IgG subclass distribution and complement activation ability of ANCA, 24 sera containing C-ANCA (cytoplasmatic) and 7 sera containing P-ANCA (perinuclear), as determined by a routine immunofluorescence test, were examined. The subclass distribution was tested by the use of immunofluorescence and ELISA technique and monoclonal antibodies to IgG subclasses. The complement activating activity was studied by the use of immunofluorescence technique and antibodies to C3c and the terminal complement complex (TCC, C5b-9), directed against a neoepitope on C9. For C-ANCA, IgG1 and IgG4 were the dominating subclasses. The subclass distribution differed from that of other autoantibodies tested and that of the total IgG subclass concentrations. For P-ANCA, the results were inconclusive, but the lack of IgG3 was striking. All of the C-ANCA-containing sera caused deposition of C3c, and 50% of the sera gave formation of TCC when reacting with ethanol-fixed granulocytes. P-ANCA-containing sera caused some C3c deposition, but not TCC formation. The unusual IgG subclass distribution for C-ANCA is possibly due to repeated antigenic stimulations and/or to T cell factors influencing the antibody isotype switching. Despite the high IgG4 activity, sera containing C-ANCA are often able to activate complement and are therefore potentially harmful.
Animals↗
Seronegative and weakly seropositive rheumatoid arthritis differ from clearly seropositive rheumatoid arthritis in HLA class II associations.
OBJECTIVE: To study the role of HLA class II genes in conferring susceptibility to seronegative vs seropositive rheumatoid arthritis (RA). METHODS: The distribution of DRB1 and DPB1 alleles in 33 seronegative, 20 weakly seropositive, 79 distinctly seropositive patients with RA, and in 181 healthy controls was determined by genomic typing: IgM rheumatoid factor (RF) seronegativity was ascertained in Waalers' latex, and ELISA tests. RESULTS: DRB1*0101/2 (encoding variants of DR1) was associated with weakly seropositive RA (and possibly seronegative RA) but not the clearly seropositive disease. In contrast DRB1*0401 and DRB1*0408 (encoding the Dw4 and Dw14.2 variants of DR4, respectively) were associated with clearly seropositive RA but were not increased among patients having weakly seropositive or seronegative RA. DRB1*0404 (encoding the Dw14.1 variant of DR4) was increased to some extent in all examined RA subsets. The distribution of DPB1 alleles in the patients was as in the controls. CONCLUSION: Seronegative and weakly seropositive RA differ from clearly seropositive RA in HLA class II associations.
Adult↗
[Complement analysis tests].
Although routine analysis of the complement system is rarely demanded, it is important from a diagnostical and therapeutical point of view to include the relevant tests when clinically required. Complement analysis should be performed when hereditary angioedema (C1 inhibitor deficiency) is suspected, and as part of investigation of patients with immunodeficiency (recurrent infections in childhood). Furthermore, complement analysis may be required in cases of recurrent systemic neisserial infections at any age, and to follow up certain autoimmune diseases. Only a few tests are available for routine purposes. These are reviewed briefly, with emphasis on collection and storage of samples prior to analysis. It is important that these guidelines be followed, to avoid misinterpretation of the results.
Angioedema↗
Low prevalence of complement deficiencies among patients with meningococcal disease in Norway.
Sera from 98 individuals who had survived meningococcal disease were analysed for classical and alternative pathway haemolytic activity and the complement components C3, C4 and properdin. No complete deficiency was found. However, median properdin concentration was only 86% in the disease group compared with the controls (P < 0.001). Properdin was also significantly lower in serogroup C disease (median 76%) compared with serogroup B disease (median 90%, P = 0.005). Severe properdin deficiency is an established risk factor for meningococcal disease. The present data may indicate that even moderately reduced properdin level can increase the risk of developing meningococcal disease.
Adolescent↗
Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants.
Serum IgG subclasses and Serum IgA were studied in 43 infants with acute bronchiolitis and 20 healthy infants. IgG subclasses were determined by a capture ELISA and IgA was quantified by turbidimetry. IgG1 concentrations were significantly lower in infants with bronchiolitis than in normal infants. The other IgG subclasses and IgA did not differ between the groups. The subgroups of infants with bronchiolitis who had previously suffered from otitis media or bronchitis, had significantly lower IgG2 than the other infants with bronchiolitis. The same was found for infants with bronchiolitis who had suffered from three or more lower respiratory tract infections. In infants who had suffered from upper or lower respiratory infections before the acute bronchiolitis, IgA was significantly higher than in infants without previous respiratory infections. Ten infants with bronchiolitis (23%) had IgG1 deficiency, that is values below the lower reference limit calculated in a population of healthy Norwegian infants. No healthy infants had any IgG1 deficiency. No infant with bronchiolitis had IgG2 or IgG3 deficiency. The low IgG1 values found in infants with acute bronchiolitis, may be one cause for infants to be more susceptible to RS virus infections.
Acute Disease↗
TCR gamma/delta+ cell subsets in the synovial membranes of patients with rheumatoid arthritis and juvenile rheumatoid arthritis.
Using a peroxidase/anti-peroxidase immunohistochemical staining method, we examined sections of inflammatory synovial membranes from 13 patients with juvenile rheumatoid arthritis (JRA) and 11 with rheumatoid arthritis (RA). The relative numbers of TCR gamma/delta+ cells and the proportions of V delta 1+ and V delta 2+ subsets were recorded in the areas of the membranes most heavily infiltrated by CD3+ cells. In the JRA group, the majority (8/13) of the membranes had TCR gamma/delta+ cells which contributed between 5 and less than 10% of the total number of CD3+ cells. In the RA synovial membranes examined, 5/11 samples had between 5 and 10% TCR gamma/delta+ cells, but in another 5 TCR gamma/delta+ cells contributed to between 10 and 20% of CD3+ cells. No significant difference was noted between the two patient groups. However, the range of values found in the RA membranes appeared to be slightly higher in comparison to previously reported values for RA synovial fluid, peripheral blood and eluted synovial membrane T cells. Analysis of the relative proportions of the V delta 1+ and V delta 2+ subsets revealed a significant dominance of V delta 1+ cells in RA membranes and approximately equal numbers of the two populations in the JRA patients. As the majority of peripheral blood TCR gamma/delta+ cells use the V delta 2 segment this suggests a preferential homing or expansion of the V delta 1+ cells in both RA and JRA synovium. The overall distribution pattern of the TCR gamma/delta+ and V delta 1+ and V delta 2+ cells was also recorded. These cells mostly accumulated in the lymphoid-like tissues and in the perivascular area in the tissues of both RA and JRA patients. Occasionally, augmented numbers of these cells were found in the subsynovial layer or in the loose connective tissue. In the majority of cases, only a few TCR gamma/delta+ cells were located in the synovial layer. The function and the possible pathogenetic importance of these TCR gamma/delta+ cells have not so far been determined.
Adolescent↗
[Determination of antinuclear antibodies in rheumatic diseases].
The presence of circulating serum antinuclear antibodies (ANA) directed against various nuclear structures is a hallmark of systemic rheumatic diseases. These diseases are characterized by overlapping clinical features and the diagnosis is not always clear-cut. Each disease has a profile of ANA specificities which is more or less specific to that disease. Therefore serological tests that define the precise specificities of ANA are of great importance for establishing the diagnosis.
Antibodies, Antinuclear↗
Occurrence of autoantibodies after solid-organ transplantation.
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Autoantibodies↗
Immunopathology of subcutaneous rheumatoid nodules.
Nodules obtained from five patients with classical seropositive rheumatoid arthritis were studied by an immunofluorescence technique using polyclonal antibodies to IgG, IgA, IgM, C3c, and fibrin, and monoclonal antibodies to the terminal (C5b-9) complement complex (reaction with a neoantigen in C9 revealed during activation), DR antigens, T cells, macrophages, and interdigitating cells. In all instances the central necrotic areas stained strongly for fibrin and more weakly for IgG, IgA, IgM, C3, and terminal complement complex. The surrounding palisading cells reacted with antibodies to DR and macrophages. In the peripheral granulomatous tissue most of the lymphocytes reacted with the antibodies to T cells, whereas various amounts of the larger mononuclear cells were stained by antibodies to DR antigens, macrophages, and interdigitating cells. In all instances the walls of some of the smaller vessels in the granulomatous tissue stained for fibrin, C3, and terminal complement complex. Plasma cells were not seen except for scattered IgM cells in one nodule. These results support the view that the palisading cells are derived from macrophages, and indicate that there is vasculitis with activation of C3 and the terminal complement pathway in the granulomatous tissue.
Arthritis, Rheumatoid↗