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Biomedical subjects

A Fasth

Publications and source records attributed to A Fasth.

At least 73 records · Page 4Linked to original sources

Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report.

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.

Antibodies, Monoclonal↗

European experience of bone-marrow transplantation for severe combined immunodeficiency.

The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.

Actuarial Analysis↗

Glomerular filtration rate and tubular involvement during acute disease and convalescence in patients with nephropathia epidemica.

Glomerular filtration rate (GFR) and tubular involvement were studied in 74 patients with serologically verified nephropathia epidemica (NE). Increased levels of serum creatinine and serum beta 2-microglobulin were documented in 96% and 99% of the patients, respectively. The mean of the lowest estimated GFR was 26 ml/min. Proximal tubular reabsorptive capacity was assessed by urinary loss of beta 2-microglobulin and cell damage by urinary activity of N-acetyl-beta-D-glucosaminidase. Both of these parameters were elevated in most of the patients during the acute phase of the disease. Increased serum levels of Tamm-Horsfall-specific IgG and/or IgA occurred in 72 of 74 patients. No patient required dialysis and there was no mortality. Six months after discharge only three patients had a GFR less than 80 ml/min as estimated by [51Cr]EDTA clearance; two of these had underlying chronic diseases and one had suffered clinically severe NE. Desmopressin tests showed decreased urine osmolarity in three patients 8 months after discharge. These three had chronic diseases, which may have contributed to the impaired tubular function. Thus, there was a markedly decreased GFR and a tubular dysfunction in the acute phase of NE. Most patients recovered within a few months and none showed evidence of chronically impaired renal function due to NE.

Acetylglucosaminidase↗

Antibody-dependent cell-mediated cytotoxicity against Tamm-Horsfall protein in acute pyelonephritis.

The cytotoxic activity of leukocytes from humans and rats with pyelonephritis were examined in an antibody-dependent cell-mediated cytotoxicity assay (ADCC) with CrCl3-treated erythrocytes coated with Tamm-Horsfall (TH) as target cells. The specificity of the ADCC was confirmed by absorption with TH urinary glycoprotein and inhibition of the ADCC activity seen with polyclonal rabbit anti-TH antisera by monoclonal mouse antibodies. The ADCC activity detected in children with acute pyelonephritis was low in the initial phase of the disease, but increased significantly 9 days after the start of antibacterial treatment. In rats with experimental pyelonephritis, ADCC activity decreased significantly with increased duration of infection. Depletion of cells adhering to carbonyl iron led to higher ADCC activity. During the course of the infection the difference in ADCC activity between effector cell preparations depleted using carbonyl iron and those not depleted decreased. The decreased ADCC activity demonstrated during acute pyelonephritis may point to mechanisms operating to diminish the risk of tissue damage.

Acute Disease↗

Incidence and prevalence of juvenile chronic arthritis: a population survey.

In a population based epidemiological survey of juvenile chronic arthritis (JCA), performed in Western Sweden in 1983, an incidence of 12/100,000 was found. The estimated prevalence was 56/100,000. Subgroup distribution showed a preponderance of mono- and pauciarticular forms. The peak age of onset was between 0 and 4 years of age. Girls predominated over boys in a ratio of 3:2. Overall, 30% were antinuclear antibody (ANA) positive, 9% rheumatoid factor (RF) positive, and eye involvement occurred in 10% of the children. The results suggest differences in population based studies of JCA compared with previously reported hospital based series.

Adolescent↗

Association between fever and the antibody response to Tamm-Horsfall protein in urinary tract infection.

The usefulness of measuring serum antibodies to Tamm-Horsfall protein (THP) for diagnosing the level of acute urinary tract infections in adult women was evaluated. There was a significant (p less than 0.001) elevation of IgG and IgA anti-THP in pregnant and non-pregnant women with acute pyelonephritis compared to women with acute cystitis. The changes in anti-THP antibody titre among patients with acute pyelonephritis varied considerably, limiting the value of determining such antibodies for diagnostic purposes. Patients with febrile infections of non-renal origin demonstrated an antibody response comparable to the pyelonephritis patients. One explanation for these results could be that fever is associated with transient rental tubular damage, thus exposing THP to the immune system. Polyclonal antibody activation seems less likely since neither an IgM antibody response to THP, nor an increase in antibody titre to poliovirus could be demonstrated.

Adult↗

Immunoglobulin for neonatal agranulocytosis.

An infant with an alloimmune agranulocytosis whose granulocyte count temporarily returned to normal during intravenous, high dosage immunoglobulin treatment is described.

Agranulocytosis↗

Renal tubular immune complex formation in mice immunized with Tamm-Horsfall protein.

Mice were given injections of rat Tamm-Horsfall protein (TH) in order to study immune complex formation in the distal nephron. After immunization, all mice had high serum levels of antibodies to TH; immune deposits consisting of IgG antibodies to TH and TH formed at the base of cells of the thick ascending limb of the loop of Henle (ALH) and distal convoluted tubule. These basal complexes were maximal in number and size within the cortical ALH, where they often radiated toward the luminal surfaces. Although the highest anti-TH antibody titers were found in animals with the most extensive deposits, antibody levels were not directly proportional to IgG deposits or to the time after immunization. The larger immune deposits were visualized by light microscopy as PAS-positive deposits. The quantity of these deposits was proportional to the time after immunization and was directly related to anti-TH antibody levels. Electron microscopy showed that these immune deposits were present within the basal and lateral intercellular spaces of the cells of the ALH. The distribution and localization of TH within the normal mouse kidney was very similar to that in rats. However, the distribution of immune complexes within the distal nephron in mice differed from rats similarly treated with TH and indicates either species differences in the distribution and/or organization of TH associated with tubular cell surfaces or that the accessibility of distal tubules to antibodies is species-dependent.

Animals↗

A critical analysis of commercially available latex particle reagents for C-reactive protein (CRP) slide agglutination tests.

C-reactive protein (CRP) was assessed in pediatric serum samples using different commercial latex reagents, which were analyzed for species origin of the coating antibodies, homogeneity and density of the latex particles, and prozone agglutinating capacity. All reagents correctly agglutinated the positive and negative control sera. The antibodies coating the particles differed with regard to species origin: one was coated with rabbit, one with horse and goat, one with horse, goat, rabbit and swine, while the reference reagent had horse, goat and rabbit antibodies. Only the monospecies specific antibody-coated latex showed obvious prozoning; this reagent also had the smallest and most homogenous latex particles and showed the most clear-cut reactions. False agglutination was observed at 7-26% according to quantitation with the spot immunoprecipitate assay, which compared favorably with radial immunodiffusion measurements. The lowest percentage of false readings was noted for the rabbit antibody-coated particles; the highest for the reagent with particles coated using antibodies from 4 different species. No reagent had satisfactory precision for the low positive sera between 10 and 40 mg CRP/l.

C-Reactive Protein↗

Abnormal B-cell proliferation associated with combined immunodeficiency, cytomegalovirus, and cultured thymus grafts.

A male infant in whom multiple recurrent multiorgan infections developed during the first six months of life was found to have combined immunodeficiency. Progressive pulmonary disease developed at age two years; cytomegalovirus (CMV) was isolated from the respiratory tract and urine. Three separate intramuscular grafts of cultured thymus fragments did not produce change in the course of the illness. Soon after age three years, IgG lambda appeared in the serum as an M-component. The patient died at age three and one-half years, with respiratory insufficiency due to pulmonary fibrosis. At autopsy, a malignant plasma cell infiltrate was limited to the retroperitoneum. The infiltrate replaced lymph node structures and surrounded nerve fascicles, which appeared necrotic, and contained CMV inclusions in ganglion cell nuclei. The plasma cells showed strong monoclonal staining for IgG lambda. Also noted was positive staining for J-chain, which has been reported previously in malignant plasma cells producing IgG. CMV could be responsible for abnormal B-cell proliferation in patients with defective immunoregulation who receive immunotherapy, as in lymphoid abnormalities associated with Epstein-Barr virus.

B-Lymphocytes↗

Autoantibodies to Tamm-Horsfall protein in acute and chronic hepatitis.

The levels of antibodies of the IgG, IgA and IgM class against the Tamm-Horsfall glycoprotein (anti-THP) were determined in 108 patients with the following diagnoses: acute hepatitis A, acute hepatitis B, acute hepatitis non-A non-B, chronic hepatitis B, chronic hepatitis non-A non-B and chronic autoimmune hepatitis. The mean levels of antibodies of the IgM class were higher in all types of hepatitis than in healthy controls, while the mean levels of anti-THP of the IgA and IgG class were increased in acute hepatitis B only. 13 of 20 patients (65%) with acute hepatitis B exhibited increased levels of anti-THP of the IgA class compared to 6-18% of the patients in the other categories. The increased levels of anti-THP of the IgA class could not be attributed to elevated serum IgA but instead were correlated with the levels of serum aminotransferase. The possible impact of this particular association of anti-THP with acute hepatitis B is discussed.

Acute Disease↗

Studies of antibodies to lipid A and Tamm-Horsfall in patients with inflammatory bowel disease.

Sera from patients with inflammatory bowel disease, ulcerative colitis (UC), or Crohn's disease (MC) were analysed for antibodies to lipid A and Tamm-Horsfall protein (TH), Escherichia coli O antigens, and food antigens, using enzyme-linked immunosorbent assay, indirect haemagglutination, and thin-layer immunoassay, respectively. C-reactive protein (CRP), an indicator of acute inflammation, was also studied. The MC and UC groups were not separated by any of the factors tested. The extent of the disease, however, seemed to influence the IgG antibody response to lipid A and TH. Patients with extended inflammatory areas in the intestine had decreased anti-lipid-A levels during the active phase of the disease compared with patients with less inflammation. In contrast, the IgG anti-TH levels were increased in these patients during both the active and inactive phases compared with less affected patients. Compared with healthy individuals, MC or UC patients showed decreased IgG anti-lipid-A levels. Both IgG and IgA anti-TH and total anti-O levels were increased compared with controls. Antibodies to cow's milk were lower in patients with inflammatory bowel disease than in the control group. CRP was increased in patients with active inflammatory bowel disease compared with inactive.

Adolescent↗

Chronic liver disease and autoantibodies to the Tamm-Horsfall protein.

Serum levels of immunoglobulin class specific antibodies to Tamm-Horsfall protein (TH) were studied in 25 patients with various liver diseases. Increased levels of TH-IgA antibodies were common in different types of liver disease, whereas high TH-IgM concentrations were observed only in patients with primary biliary cirrhosis or chronic active hepatitis. The occurrence of high concentrations of TH antibodies was not related to the occurrence of renal tubular acidosis detected by an acidification test, but the elevation of TH-IgA was significantly correlated to high levels of total serum IgA. An indirect immunofluorescence method did not demonstrate any cross-reaction between TH and liver tissue.

Acidosis, Renal Tubular↗