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O J Mellbye

Publications and source records attributed to O J Mellbye.

At least 19 recordsLinked to original sources
PubMed2002

Immunophenotypic analyses of CD34(+) cell subsets in bone marrow from HIV-infected patients during highly- active antiretroviral therapy.

BACKGROUND: Because increased bone marrow lymphopoiesis might contribute to immunologic reconstitution during highly-active antiretroviral therapy (HAART), we examined the effect of HAART on CD34(+) cell subsets in bone marrow from HIV-infected patients. MATERIALS AND METHODS: In 12 HIV-infected patients, bone marrow and peripheral blood were collected before then 4 and 26 weeks after initiating HAART. Bone marrow in 28 HIV-seronegative controls was also examined. Immunophenotypic analyses of CD34(+) cell subsets in bone marrow were performed by flow cytometry. RESULTS: Our main findings in bone marrow were: (i) HIV-infected patients had increased proportions of CD34(+)cells expressing T- and B-cell markers before initiating HAART; (ii) in contrast, these patients had decreased proportions of CD34(+) cells expressing myeloid-associated markers; (iii) although HAART induced an increase in peripheral T-cell counts, the percentage of CD34(+)cells expressing T-cell markers tended to decrease during such therapy; (iv) HAART induced a decrease in serum IgG accompanied by a slight decrease in the proportion of CD34(+)cells expressing B-cell markers; (v) in contrast, HAART induced a significant increase in peripheral granulocyte counts, accompanied by a slightly increased proportion of CD34(+) cells expressing myeloid-associated molecules. CONCLUSION: Our findings are compatible with an HIV-related block in T-cell differentiation, leading to accumulation of T-cell progenitors in bone marrow, and such a block may be removed by HAART.

Adult↗
PubMed2000

The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease.

Abnormal deposition of proteins, including monoclonal immunoglobulin gamma-heavy chains, may cause tissue damage and organ dysfunction. We here report the amino acid sequence of the free gamma-heavy chains present in serum and urine of the first reported case (patient G. L.) of synovial heavy chain deposition disease. The protein was heavily deleted and consisted of the hinge, in addition to the CH2 and CH3 domains, in a dimeric form, thus lacking its variable domain as well as the CH1 domain. The sequence was consistent with the gamma 3 subclass (gamma 3GL). Gm typing revealed the gamma 3 allotypes G3m(b0) and G3m(b1) in accordance with the residues Pro123, Phe128, Thr171 and Phe268 in gamma 3GL. Furthermore, the gamma 3GL molecule was glycosylated at Asn in position 129. Finally, the gamma 3GL protein was shown to contain a typical binding site for the first complement component, C1q, namely the residues Glu150, Lys152 and Lys154, with the potential of binding and activating complement, causing tissue damage following deposition.

Amino Acid Sequence↗
PubMed1999

C1-inhibitor attenuates hyperacute rejection and inhibits complement, leukocyte and platelet activation in an ex vivo pig-to-human perfusion model.

Xenotransplantation may be a future alternative due to increased shortage of organs. Classical complement activation is central in hyperacute rejection in pig-to-human combinations. We investigated the effects of C1-inhibitor (C1-INH), a regulator of the complement and contact systems, on hyperacute rejection. Pig kidneys were perfused with fresh human blood to which either C1-INH (n = 6) or human serum albumin (n = 6) was added. The survival of the C1-INH perfused kidneys (mean 327 min) was significantly longer (p < 0.00001) than the controls (79 min). C1-INH substantially inhibited complement activation (C1rs-C1-INH complexes, C4bc, C3bc and terminal complement complex) (p < 0.001 for all) compared with the marked complement activation in the controls. No contact activation was found. Leukocytes and platelets were substantially activated (counts, myeloperoxidase, beta-thromboglobulin, thrombospondin, soluble P-selectin) in the control group, and this activation was markedly reduced by C1-INH (p < 0.02 for all). Immunohistochemistry showed less C1q, C3, TCC, IgG and fibrin deposition in the C1-INH group. C1-INH may be useful to attenuate hyperacute rejection, probably through inhibition of complement. The reduced activation of neutrophils and platelets may mainly be secondary to inhibition of complement.

Animals↗
PubMed1999

Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts.

Compstatin, a newly described C3-binding peptide, inhibits complement activation by blocking C3 convertase-mediated cleavage of C3. As the complement activation is an essential part of the rejection reaction, we evaluated the ability of Compstatin to delay or prevent hyperacute rejection in an ex vivo xenograft model. Pig kidneys were perfused with fresh human blood containing either Compstatin (n=6) or a control agent (n=6). Graft survival and activation of complement, leukocytes and platelets both in the fluid-phase and in the tissue were examined. The survival of the Compstatin-perfused kidneys (median, 380 min) was significantly (P=0.0036) longer than that of the controls (median, 90 min). The classical complement pathway (C1rs-C1inhibitor and C4bc) was significantly and equally activated in both groups during the first 60 min. C3 activation products increased fivefold and terminal complement complex eightfold in the control group, but no increase occurred in the Compstatin group during this period. Immunohistochemistry showed less C3 and fibrin deposition and immune electron microscopy showed less terminal SC5b-9 complement complex deposition in the Compstatin group. A significant change in total white cells, neutrophils, myeloperoxidase, and expression of the surface activation markers CD11b (CR3) and CD35 (CR1) and CD62L (L-selectin) was observed in both groups. Leukocyte activation was lower in the Compstatin group but the difference was not statistically significant. There were no differences in platelet counts, thrombospondin, soluble P-selectin or beta-thromboglobulin between the groups. We conclude that Compstatin prolongs graft survival and suggest that it may be a useful agent for attenuating hyperacute rejection by inhibiting C3 and thus terminal complement pathway activation.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

[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↗
PubMed1993

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↗