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Biomedical subjects

G Uko

Publications and source records attributed to G Uko.

11 recordsLinked to original sources
PubMed2000

Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen.

Some human subjects vaccinated with hepatitis B surface antigen (HBsAg) do not produce antibodies to the vaccine (nonresponders). The mechanism for nonresponse is unknown. To understand the response and nonresponse to nominal antigens better, we determined the level and kinetics of cytokine secretion in response to HBsAg and tetanus toxoid (TT) by peripheral blood mononuclear cells (PBMC) in vitro from HBsAg vaccine responders and nonresponders and from individuals naive to HBsAg. Proliferating PBMC secreted peak levels of interleukin-2 (IL-2) at 2 days and peak levels of tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), IL-4 and IL-10 at 3-6 days post-stimulation. In contrast, nonproliferating PBMC (whether from nonresponders, naive subjects or weak responders) did not produce detectable levels of TNF-beta or IFN-gamma, nor was IL-4 or IL-10 produced significantly, and that produced had a different kinetic profile from that of proliferating PBMC. HBsAg-specific cytokine production by PBMC from strong responders broadly paralleled their cytokine responses to TT. Cellular cytokine mRNA levels measured by reverse transcriptase-polymerase chain reaction corroborated the secreted cytokine results. The anti-HBsAg- and anti-TT-specific T cell cytokine responses were mixed Th(1/2)-like and donor-specific. An HBsAg-specific cytokine response, but not a TT-specific cytokine response, was completely missing in nonresponders. These data suggest that the T cell defect of HBsAg nonresponse is not due to a skewed cytokine profile.

Adult↗
PubMed1999

CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.

We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.

Adult↗
PubMed1988

HLA, C4, Bf, Gm and autoantibodies in rheumatoid arthritis.

Sera from 48 subjects with rheumatoid arthritis (RA), more than 80% of which were seropositive, were examined for the presence of antibodies to intact nuclei (ANA) by immunofluorescence, extractable nuclear antigens (ENA), double-stranded DNA by immunoassay and immunoglobulins, i.e. rheumatoid factors (RF) by haemagglutination. The genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex and Gm immunoglobulin allotypic markers were all analysed in relation to various parameters of these autoantibodies. The only significant association to emerge was between low ENA antibody affinities and the Bf Fs phenotype (p less than 0.02). Although weak associations between individual autoantibody parameters and the other immunogenetic markers were detected, there were no significant HLA, C4 or Gm association with either ANA subsets or RF, a finding which agrees with, and also extends previous HLA studies of predominantly seropositive RA cohorts.

Adolescent↗
PubMed1986

Serum C4 concentration in the monitoring of systemic lupus erythematosus: requirement for C4 allotyping.

We have examined the influence of genetic and other factors on the serum concentration of the fourth component of complement (C4) in four patients with systemic lupus erythematosus (SLE) studied over 3 to 8 years. Complement allotyping was performed to determine the number of C4 null genes in each patient. Two patients with C4 null genes had relatively low serum C4 concentrations with normal serum anti-DNA binding and no evidence of active disease. By contrast two patients without null alleles appeared to be consuming C4 when the serum C4 concentrations were within the conventional reference range. We therefore propose the use of appropriate reference ranges adjusted for the number of null alleles. Such adjusted reference ranges may improve the utility of serum C4 concentration in monitoring disease activity.

Alleles↗
PubMed1986

Reference ranges for serum C4 concentrations in subjects with and without C4 null alleles.

Serum C4 concentrations were measured in 102 healthy subjects and 90 subjects with type I diabetes mellitus. A wide range was observed in the group as a whole (0.08-0.67 g/l; mean = 0.26 g/l; SEM = 0.01 g/l). After C4 allotyping it was possible to subgroup 134 of these subjects according to the number of C4 null alleles present. C4 concentrations in the group with two null alleles were lower than in the group without null alleles (mean 0.2 v 0.37 g/l; p less than 0.001). C4 concentrations in the group with one C4 null allele were intermediate and significantly different from those of the group without null alleles (mean 0.24 v 0.37 g/l; p less than 0.001). Appropriate analysis has defined reference ranges for serum C4 concentrations in subjects with two, one, or zero C4 null alleles. Interpretation of low serum C4 concentrations should take account of the number of C4 null alleles present.

Adult↗
PubMed1986

Extractable nuclear antigen (ENA) autoantibodies in SLE: an immunogenetic relationship with HLA, C4 and Bf alleles.

Sera from 36 subjects with systemic lupus erythematosus (SLE) were examined for extractable nuclear antigen (ENA) autoantibodies by immunoassay with the ribonucleoprotein (RNP) subset being determined by immunodiffusion. The prevalence of the genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex on chromosome 6 were analysed in relation to various parameters of these autoantibodies. The following associations were observed: The lowest ENA antibody titres of the RNP negative group were associated with HLA A9 (P less than 0.05), while the lowest RNA-ase sensitive ENA (RSE) subset antibody levels were associated with HLA Dr 1 (P less than 0.05). For the complement markers, C4 AQo was associated with the lowest affinity ENA antibodies (P less than 0.05), while the BF F allele and Fs phenotype had lower RSE antibody levels than did the S allele (P less than 0.05) and the SS phenotype (P less than 0.05) respectively. This study demonstrated diverse association between various MHC markers and ENA antibody parameters, indicating that there are distinctive immunogenetic influences over ENA autoantibodies in SLE.

Adolescent↗
PubMed1985

Secondary Sjögren's syndrome and chromosome six markers.

Patients with Sjögren's syndrome (SS) in association with either Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) or Sclerodactyly were tested for HLA-A, B and Dr antigens and the phenotypes of the 4th component of complement (CA). Significant associations were identified between HLA-Bw62, Dr4, C4B2.9, C4A8 and females with SS-RA. The MHC antigen frequencies noted for secondary Sjögren's syndrome differed from those reported for their respective primary diseases and the implications of these observations are discussed.

Adult↗
PubMed1985

CR1 deficiency in SLE: acquired or genetic?

Erythrocytes from 30 patients suffering from systemic lupus erythematosus (SLE) were tested for CR1 activity by an immune adherence haemagglutination technique. Defective CR1 activity (CR1D) was found in 11 (37%) of the patients on initial testing. On repeat testings, however, CR1 activity often varied from time to time and was shown to be inversely related to serum anti-DNA binding and apparent complement activation in vivo. Two of the 19 patients with normal CR1 activity acquired CR1D during the study. One patient with previously defective CR1 attained normal activity in the course of the study. The increased occurrence of CR1D in patients with SLE is largely or wholly acquired rather than genetically determined.

Adolescent↗
PubMed1983

Complement allotyping in SLE: association with C4A null.

Immunogenetic factors are important in systemic lupus erythematosus (SLE) and deficiency of a number of complement components is often associated with a lupus-like illness. The complement components Bf, C2 and C4 are encoded within the human major histocompatibility complex (MHC) and are polymorphic. A study of HLA and Bf and C4 polymorphism in 43 patients with SLE was undertaken firstly, to determine whether partial deficiency of C2 and C4 may predispose to disease and secondly, because it may allow the better definition of important supratypes associated with the disease and which may include the relevant disease gene(s). An increased frequency of C4A null alleles has been shown in SLE, with a minimal estimated C4A null gene frequency of 0.32 versus 0.20, but no case of partial C2 deficiency was identified. These results may indicate a direct role for partial C4 deficiency or that C4A null may be a marker for an important supratype which includes the relevant disease gene(s).

Complement C2↗