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Biomedical subjects

G Senaldi

Publications and source records attributed to G Senaldi.

At least 19 recordsLinked to original sources
PubMed1992

Naturally occurring soluble CD4 in patients with human immunodeficiency virus infection.

To investigate its use as a marker of disease severity, serum soluble CD4 (sCD4) was measured by ELISA in patients with human immunodeficiency virus (HIV) infection. Levels of sCD4 were higher in patients than in controls (P less than .001) but did not increase with disease severity. sCD4 release per CD4 lymphocyte showed a linear increase with disease severity and performed as well as beta 2-microglobulin, a widely used marker. To study the role of sCD4 in the pathogenesis of HIV infection, an ELISA to detect sCD4 complexed with glycoprotein 120 (gp120) HIV envelope protein was developed. Preformed sCD4-gp120 complexes were not detectable in patient serum, but addition of recombinant gp120 showed that circulating sCD4 is capable of binding HIV envelope proteins. This study indicates that the sCD4-to-CD4 lymphocyte ratio increases linearly with disease severity and may be a useful marker of CD4 lymphocyte damage. In addition, serum sCD4 can bind viral particles, which may have implications for the use of recombinant sCD4 as a therapy in HIV infection.

AIDS-Related Complex↗
PubMed1992

Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis.

The portal tract mononuclear cell infiltrate has been characterised in 28 liver biopsy samples showing features of chronic aggressive hepatitis from 12 patients with autoimmune chronic active hepatitis, 12 with primary sclerosing cholangitis, and four with other chronic liver diseases (two with alpha 1-antitrypsin deficiency, one with Wilson's disease, and one with chronic hepatitis B infection). In all patients liver disease had started in childhood. The mononuclear cell infiltrate was investigated by a two step immunoperoxidase technique using monoclonal antibodies to: total, alpha/beta T cell receptor positive, helper/inducer, suppressor/cytotoxic T lymphocytes; B lymphocytes; killer/natural killer cells; monocyte/macrophages; and to the activation markers HLA-DR antigens, interleukin 2 receptor (IL-2R), transferrin receptor, and 4F2Ag. In all samples the infiltrate consisted of mainly alpha/beta T cell receptor T lymphocytes. Although T helper/inducer cells predominated in patients with autoimmune chronic active hepatitis, T suppressor/cytotoxic lymphocytes were preponderant in patients with primary sclerosing cholangitis and the other chronic liver diseases. Killer/natural killer cells accounted for up to 25% of the mononuclear cell infiltrate in patients with autoimmune chronic active hepatitis, being rare or absent in the other diseases. Monocytes/macrophages were always found, but they were more numerous in primary sclerosing cholangitis than in the other chronic liver diseases. B lymphocytes were rare or absent in all subjects. Activated mononuclear cells were present in all subjects, but although in patients with autoimmune chronic active hepatitis and primary sclerosing cholangitis most cells of the infiltrate expressed HLA-DR antigens and up to 75% IL-2R, in other forms of chronic liver diseases HLA-DR positive cells were less common and IL-2R positive cells ere rare or absent. These results show that the cells responsible for the histological characteristics of chronic aggressive hepatitis vary in their functional phenotype and state of activation according to the type of underlying liver disorder, confirming the involvement of different pathogenetic mechanisms.

Adolescent↗
PubMed1992

Complement activation in neonatal infection.

To investigate the usefulness of indices of complement activation in the diagnosis of infections in the neonatal period, activation products C4d, Ba, and C3d were measured in 42 babies with a putative diagnosis of infection based on clinical/laboratory criteria, and compared with conventional clinical and haematological criteria of infection and with C reactive protein. The diagnosis of sepsis was confirmed by culture and identification of organisms in 17. Fourteen babies in whom infection was not suspected formed the control group. In babies with proved infection, concentrations of the fragments C4d, Ba, and C3d were higher than in babies with suspected infection in whom microbiological tests were negative, and concentrations of Ba and C3d were higher than in controls. C reactive protein and the platelet count were not significantly different in babies with proved infection and those with negative microbiological tests, but in the latter, C reactive protein concentrations were higher than in controls. Of the indices studied, high concentrations of Ba predicted microbiologically proved infection with the highest sensitivity (47.1%) and specificity (92.0%). Ba thus seems to be useful as an early indicator of infection in the neonatal period.

Analysis of Variance↗
PubMed1992

Activation of the classical complement pathway in spontaneous bacterial peritonitis.

To investigate the possibility that low complement concentrations in the plasma and ascites of patients with severe liver disease could be secondary to complement consumption, complement activation was studied in 32 patients with severe liver disease, 11 of whom had spontaneous bacterial peritonitis (SBP). In patients with SBP, plasma C3 and C4 were significantly lower than in uninfected patients (mean values 0.74 v 1.13 g/l, p less than 0.01 and 0.20 v 0.28 g/l, p less than 0.05 respectively). Plasma complement activation via the classical pathway, as shown by C4d/C4, was significantly increased in patients with SBP compared with uninfected patients (37.3 v 22.2, p less than 0.01) as was C3d/C3 (14.0 v 8.11, p less than 0.01), but there was no significant difference in Ba/B between SBP and uninfected patients. Ascitic C3 concentrations were higher in patients without SBP than in infected patients (0.37 v 0.08 g/l, p less than 0.05), as were factor B values (0.11 v 0.03 g/l, p less than 0.05). There was no significant difference in ascitic C4 concentrations in patients with SBP compared with uninfected patients (0.03 v 0.07 g/l). Although consumption of C3, as shown by C3d/C3 in ascites, was increased in infected patients compared with uninfected patients (79.1 v 36.1, p less than 0.05), there was no difference in ascitic complement activation between the groups for either the classical or alternative pathways. In SBP, decreased plasma C3 and C4 are primarily caused by increased activation of the classical pathway and not impaired hepatic synthesis. Activation and consumption of C3 is one factor causing the low ascitic C3 concentrations observed in SBP.

Adult↗
PubMed1991

Anticardiolipin antibodies in patients from Malaysia with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is highly prevalent in Malaysia, which has a mixed population of Malays, Chinese, and Indians. A quantitative enzyme linked immunosorbent assay (ELISA) was used to determine anticardiolipin antibody (aCL) levels (total immunoglobulin, IgG, and IgM) in 200 patients with SLE (164 Chinese, 26 Malay, and 10 Indian) attending the University Hospital of Kuala Lumpur, Malaysia, and 103 matched controls. Only 33 (16.5%) of the patients had raised aCL levels; 26 had raised IgG aCL, five IgM aCL, and two both IgG and IgM aCL. There was a low prevalence of raised levels of aCL in the population studied, which was seen in conjunction with a rare occurrence of thrombosis. The classical association of high aCL levels with thrombocytopenia and recurrent abortions was noted, though not with cerebral disease. The low prevalence of aCL in this study population of mixed racial origin contrasts with findings in European patients with SLE and lends support to the influence of local factors, be they genetic or environmental, on the clinical manifestations of this disease.

Abortion, Habitual↗
PubMed1991

Influence of C4 null alleles on C4 activation in systemic lupus erythematosus.

Deficiencies of early components of the classical complement pathway are known to be associated with systemic lupus erythematosus (SLE). C4 null alleles, C4A Q0 and C4B Q0, are prime candidates for the major histocompatibility complex associated factor which determines susceptibility to SLE. There is poor correlation, however, between the presence of low concentrations of C4 and possession of C4 null alleles, and thus the basis of the association between C4A Q0, C4B Q0 and SLE remains obscure. The possibility that activation of C4 may be related to the possession of C4 null alleles was examined. C4 phenotypes were investigated, and C4 concentration and activation were estimated in patients with SLE. C4 activation was determined by measuring the concentration of C4d--a split product of C4. Twenty five of 35 patients had C4 phenotypes which include null alleles. No association between low C4 concentrations and C4 null alleles was found, but a significant association between low C4d concentrations and C4 phenotypes including null alleles, particularly those with C4A Q0, was noted. No correlation between concentrations of C4 and C4d was found. These results show an influence of C4 null alleles on the activation of the C4 molecule, which is independent of the concentration of C4. The possession of silent genes coding for C4 null alleles might predispose to SLE by conditioning poor C4 activation, a critical event for the clearance of immune complexes mediated by the classical complement pathway.

Alleles↗
PubMed1991

Class I and class II major histocompatibility complex antigens on hepatocytes: importance of the method of detection and expression in histologically normal and diseased livers.

Methodological differences in major histocompatibility complex (MHC) antigen detection were investigated on isolated, viable hepatocytes and cryostat hepatic sections from 27 children with liver disorders, six of whom had normal histology. Class I antigens were constantly found on sections using a three step immunoperoxidase technique after acetone/chloroform fixation, other techniques being less sensitive, or on isolated hepatocytes by indirect immunofluorescence alone. With mechanical isolation the percentage of positivity ranged from 85 to 100%, while with collagenase isolation it ranged from 22 to 49% on immediate testing, and from 53 to 80% after 24 hour incubation. Class II antigens were only detected in one patient with autoimmune chronic active hepatitis and two with primary sclerosing cholangitis. Flow cytofluorimetric analysis in 11 cases confirmed class II or class I positivity, or both, on isolated hepatocytes, allowing MHC antigen expression on hepatocytes to be measured. Class I and II antigen detection on hepatocytes is influenced by the technique used. Although class I antigens are invariably expressed on hepatocytes, class II antigens are only found on hepatocytes from patients with immune mediated liver disorders.

Adolescent↗
PubMed1990

Class I and class II major histocompatibility complex antigen expression on hepatocytes: a study in children with liver disease.

Controversy exists regarding major histocompatibility complex antigen expression on hepatocytes. In this study, hepatocyte expression of class I and II major histocompatibility complex antigens was investigated in diseased and normal livers, using indirect immunofluorescent staining of mechanically isolated, viable hepatocytes. Hepatocytes were obtained from 76 children: 10 with autoimmune chronic active hepatitis, nine with primary sclerosing cholangitis, nine with chronic hepatitis B virus infection, five after liver transplantation, 19 with extrahepatic biliary atresia, 11 with alpha 1-antitrypsin deficiency, four with idiopathic neonatal hepatitis and nine with histologically normal liver. Immunohistochemistry was performed in all cases; flow cytofluorimetry was performed for class I antigens in 38 cases and performed for class II antigens in 18 cases. From three children with autoimmune chronic active hepatitis and two with chronic hepatitis B virus infection, isolated hepatocytes were also incubated with gamma-interferon before staining and analysis. By fluorescence microscopy, class I antigens were detected on hepatocytes from all children, the highest percentage (100%) of positive cells and the most intense staining were observed in untreated patients with autoimmune chronic active hepatitis or primary sclerosing cholangitis and in those with acute rejection of a liver transplant. Reduced class I antigen expression occurred in chronic hepatitis B virus infection. Class II antigens were only detected on hepatocytes from eight patients: three with autoimmune chronic active hepatitis and five with primary sclerosing cholangitis, all untreated. Flow cytofluorimetric analysis confirmed the results obtained by fluorescence microscopy, but it also demonstrated a weak class II antigen expression during liver allograft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1990

Complement activation products in idiopathic pulmonary fibrosis: relevance of fragment Ba to disease severity.

Immune complexes have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a chronic inflammatory disease of unknown etiology. Using newly developed techniques to measure complement fragments, we assessed whether complement activation occurs in IPF and its relationship to circulating immune complexes (CIC), disease severity, and prognosis. We measured the fragments C3d, C4d, and Ba of the common, classical, and alternative pathway, respectively, along with the components C3, C4, and Factor B and CIC, in 18 patients and 19 healthy subjects. The fragment to parent molecule ratios C3d/C3, C4d/C4, and Ba/Factor B were derived. Complement determinations were repeated in 14 of the patients on a second occasion separated by 8-33 months (median 17 months) from the first. All parameters were higher in patients than controls, and the difference between the two groups was significant for C3d, C4d/C4, C3, CIC (P less than 0.05) and for C4d and Ba (P less than 0.01). Fragment Ba was found to correlate with disease duration and indices of disease severity, i.e., positively with the dyspnoea score (Rs = 0.44, P less than 0.04), the physiological score (Rs = 0.50, P less than 0.02), the fibrosis score (Rs = 0.45, P less than 0.04), and a composite clinical, radiological, and physiological score (Rs = 0.48, P less than 0.03) and negatively with the forced vital capacity (Rs = -0.47, P less than 0.03). Ba was higher in those patients who deteriorated on follow-up analysis than those who improved or remained unchanged (P less than 0.04). These results show that conversion products of all complement pathways are increased in IPF and demonstrate classical pathway activation. They also show that the measurement of Ba might prove a useful laboratory test of disease severity in this condition.

Adult↗
PubMed1990

Activation of the complement system in human immunodeficiency virus infection: relevance of the classical pathway to pathogenesis and disease severity.

In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection.

Adult↗
PubMed1990

Antireticulin antibody in systemic sclerosis.

The prevalence, immunoglobulin class, and IgG subclass of antireticulin antibody in the serum samples of 32 patients with systemic sclerosis were investigated by indirect immunofluorescence on unfixed rodent tissue. Antireticulin antibody was present in 22/32 (69%) of patients and belonged to the IgG class in 19/22 (86%), the IgA class in 13/22 (59%), and the IgM class in 6/22 (27%) of positive sera. IgG1 was the predominant subclass of IgG antireticulin antibody, occurring either alone or in association with IgG3 in 12/19 cases (63%). Thus antireticulin antibody of the IgG and IgA classes is found in most patients with systemic sclerosis. The finding of an autoantibody with reactivity for collagen-like fibres in systemic sclerosis indicates that the antibody has a potential role in the pathogenesis of the disease, and as it belongs to the IgA class this suggests that it arises in response to antigens presented to the immune system at the mucosal level.

Adolescent↗
PubMed1989

Activation of the complement system in systemic sclerosis. Relationship to clinical severity.

Using newly developed techniques, we investigated the complement pathways and the extent of their activation in patients with systemic sclerosis (SSc) of both the diffuse cutaneous and limited cutaneous types. Plasma levels of the fragments C3d, C4d, and Ba were measured in patients with SSc and in matched control subjects. All fragments and ratios were higher in SSc patients than in controls (P less than 0.05), demonstrating that complement activation occurs in SSc. Levels of C3d, C3d:C3, Ba, and Ba:factor B were higher in patients with diffuse cutaneous SSc patients than in controls (P less than 0.01). C3d, C3d:C3, C4d, and C4d:C4 levels were also higher in patients with limited cutaneous SSc than in controls (P less than 0.05). These results show that complement activation occurs in SSc patients and that it reflects clinical severity. Complement activation may therefore have a pathogenetic role in SSc, and its measurement may prove useful in monitoring the disease.

Adult↗
PubMed1989

Activation of the complement system in primary sclerosing cholangitis.

Recent evidence, including the presence of circulating immune complexes, suggests that abnormalities of humoral immunity may be important in the pathogenesis of primary sclerosing cholangitis. The aim of the present study was to determine whether activation of the complement system is present in patients with this disease, as this would be supportive evidence of a role for circulating immune complexes in primary sclerosing cholangitis. Plasma complement fragments C3d and C4d, and serum C3 and C4, their respective parent molecules, have been assayed. Both C3d and C4d were elevated in patients with primary sclerosing cholangitis compared with patients with extrahepatic obstructive cholestasis and normal controls (p less than 0.01 in all instances). C3 was elevated in both patient groups, in whom it was similar, compared with normal controls (p less than 0.001 in both cases), whereas C4 was similar in all groups. Elevated levels of circulating immune complexes were identified in 21 of 24 (88%) patients with primary sclerosing cholangitis, but in none of the normal controls. These findings support the hypothesis that in primary sclerosing cholangitis circulating immune complexes are associated with activation of complement via the classical pathway.

Adult↗